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Sample records for arsenic metabolites plasma

  1. Urinary Arsenic Metabolites of Subjects Exposed to Elevated Arsenic Present in Coal in Shaanxi Province, China

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    Linsheng Yang

    2011-06-01

    Full Text Available In contrast to arsenic (As poisoning caused by naturally occurring inorganic arsenic-contaminated water consumption, coal arsenic poisoning (CAP induced by elevated arsenic exposure from coal combustion has rarely been reported. In this study, the concentrations and distributions of urinary arsenic metabolites in 57 volunteers (36 subjects with skin lesions and 21 subjects without skin lesions, who had been exposed to elevated levels of arsenic present in coal in Changshapu village in the south of Shaanxi Province (China, were reported. The urinary arsenic species, including inorganic arsenic (iAs [arsenite (iAsIII and arsenate (iAsV], monomethylarsonic acid (MMAV and dimethylarsinic acid (DMAV, were determined by high-performance liquid chromatography (HPLC combined with inductively coupled plasma mass spectroscopy (ICP-MS. The relative distributions of arsenic species, the primary methylation index (PMI = MMAV/iAs and the secondary methylation index (SMI = DMAV/MMAV were calculated to assess the metabolism of arsenic. Subjects with skin lesions had a higher concentration of urinary arsenic and a lower arsenic methylation capability than subjects without skin lesions. Women had a significantly higher methylation capability of arsenic than men, as defined by a higher percent DMAV and SMI in urine among women, which was the one possible interpretation of women with a higher concentration of urinary arsenic but lower susceptibility to skin lesions. The findings suggested that not only the dose of arsenic exposure but also the arsenic methylation capability have an impact on the individual susceptibility to skin lesions induced by coal arsenic exposure.

  2. Analysis of arsenical metabolites in biological samples.

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    Hernandez-Zavala, Araceli; Drobna, Zuzana; Styblo, Miroslav; Thomas, David J

    2009-11-01

    Quantitation of iAs and its methylated metabolites in biological samples provides dosimetric information needed to understand dose-response relations. Here, methods are described for separation of inorganic and mono-, di-, and trimethylated arsenicals by thin layer chromatography. This method has been extensively used to track the metabolism of the radionuclide [(73)As] in a variety of in vitro assay systems. In addition, a hydride generation-cryotrapping-gas chromatography-atomic absorption spectrometric method is described for the quantitation of arsenicals in biological samples. This method uses pH-selective hydride generation to differentiate among arsenicals containing trivalent or pentavalent arsenic.

  3. Arsenic metabolites in humans after ingestion of wakame seaweed

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    Hata A.

    2013-04-01

    Full Text Available Seaweed contains large amounts of various arsenic compounds such as arsenosugars (AsSugs, but their relative toxicities have not yet been fully evaluated. A risk evaluation of dietary arsenic would be necessary. After developing an arsenic speciation analysis of wakame seaweed (Undaria pinnatifida, we conducted a wakame ingestion experiment using volunteers. Five volunteers ingested 300 g of commercial wakame after refraining from seafood for 5 days. Arsenic metabolites in the urine were monitored over a 5-day period after ingestion. Total arsenic concentration of the wakame seaweed was 34.3 ± 2.1 mg arsenic/kg (dry weight, n = 3. Two AsSugs, 3-[5′-deoxy-5′-(dimethyl-arsinoyl-β-ribofuranosyloxy]-propylene glycol (AsSug328 and 3-[5′-deoxy-5′-(dimethyl-arsinoyl-β- ribofuranosyl-oxy]-2-hydroxypropyl-2,3-dihydroxy-propyl phosphate (AsSug482 were detected, but arsenobetaine, dimethylarsinic acid (DMA, monomethylarsonic acid, and inorganic arsenics (iAs were not detected. The major peak was AsSug328, which comprised 89% of the total arsenic. Approximately 30% of the total arsenic ingested was excreted in the urine during the 5-day observation. Five arsenic compounds were detected in the urine after ingestion, the major one being DMA, which comprised 58.1 ± 5.0% of the total urinary arsenic excreted over the 5 days. DMA was believed to be metabolized not from iAs but from AsSugs, and its biological half-time was approximately 13 h.

  4. Cytotoxic effects of S-(dimethylarsino)-glutathione: A putative intermediate metabolite of inorganic arsenicals

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    Hirano, Seishiro; Kobayashi, Yayoi

    2006-01-01

    Glutathione (GSH) plays an important role in the metabolism of arsenite and arsenate by generating arsenic-glutathione complexes. Although dimethylarsinic acid (DMA V ) is the major metabolite of inorganic arsenicals (iAs) in urine, it is not clear how DMA V is produced from iAs. In the present study we report that S-(dimethylarsino)-glutathione (DMA III (SG)), a putative precursor of dimethylarsinic acid DMA V , was unstable in the culture medium without excess GSH and generated volatile substances which were highly cytotoxic for both rat heart microvascular endothelial cells and HL60, a human leukemia cell line. Cytotoxicity of DMA III (SG) was higher than that of iAs and its LC 5 value was calculated to be 7.8 μM in the endothelial cells. To our surprise DMA III (SG) effectively killed cells in the neighbor wells of the same multi-well dish, indicating that volatile toxic compounds generated from DMA III (SG) in the culture medium. High performance lipid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS) analyses suggested that the freshly generated volatile compounds dissolved into aqueous solution and formed an unstable arsenic compound and the unstable compound was further converted to DMA V . These results suggested that DMA III (SG) exerts its cytotoxicity by generating volatile arsenicals and is implicated in the metabolic conversion of inorganic arsenicals into DMA V , a major final metabolite of inorganic arsenicals in most mammals

  5. Biological monitoring of arsenic exposure of gallium arsenide- and inorganic arsenic-exposed workers by determination of inorganic arsenic and its metabolites in urine and hair

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    Yamauchi, H.; Takahashi, K.; Mashiko, M.; Yamamura, Y. (St. Marianna Univ. School of Medicine, Kawasaki (Japan))

    1989-11-01

    In an attempt to establish a method for biological monitoring of inorganic arsenic exposure, the chemical species of arsenic were measured in the urine and hair of gallium arsenide (GaAs) plant and copper smelter workers. Determination of urinary inorganic arsenic concentration proved sensitive enough to monitor the low-level inorganic arsenic exposure of the GaAs plant workers. The urinary inorganic arsenic concentration in the copper smelter workers was far higher than that of a control group and was associated with high urinary concentrations of the inorganic arsenic metabolites, methylarsonic acid (MAA) and dimethylarsinic acid (DMAA). The results established a method for exposure level-dependent biological monitoring of inorganic arsenic exposure. Low-level exposures could be monitored only by determining urinary inorganic arsenic concentration. High-level exposures clearly produced an increased urinary inorganic arsenic concentration, with an increased sum of urinary concentrations of inorganic arsenic and its metabolites (inorganic arsenic + MAA + DMAA). The determination of urinary arsenobetaine proved to determine specifically the seafood-derived arsenic, allowing this arsenic to be distinguished clearly from the arsenic from occupational exposure. Monitoring arsenic exposure by determining the arsenic in the hair appeared to be of value only when used for environmental monitoring of arsenic contamination rather than for biological monitoring.

  6. Airborne arsenic and urinary excretion of arsenic metabolites during boiler cleaning operations in a Slovak coal-fired power plant

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    Yager, J.W.; Hicks, J.B.; Fabianova, N. [EPRI, Palo Alto, CA (United States). Environment Group

    1997-08-01

    Little information is available on the relationship between occupational exposure to inorganic arsenic in coal fly ash and urinary excretion of arsenic metabolites. This study was undertaken in a coal-fired power plant in Slovakia during a routine maintenance outage. Arsenic was measured in the breathing zone of workers during 5 consecutive workdays, and urine samples were obtained for analysis of arsenic metabolites-inorganic arsenic (As), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) prior to the start of each shift. Results from a small number of cascade impacter air samples indicated that approximately 90% of total particle mass and arsenic was present in particle size fractions {ge} 3.5 {mu}m. The 8-hr time-weighted average (TWA) mean arsenic air concentration was 48.3 {mu}g/m{sup 3} (range 0.17-375.2) and the mean sum of urinary arsenic (Sigma As) metabolites was 16.9 {mu}g As/g creatinine (range 2.6-50.8). For an 8-hr TWA of 10 {mu}g/m{sup 3} arsenic from coal fly ash, the predicted mean concentration f the Sigma As urinary metabolites was 13.2 {mu}g As/g creatinine. Comparisons with previously published studies of exposure to arsenic trioxide vapors and dusts in copper smelters suggest that bioavailability of arsenic from airborne coal fly ash (as indicated by urinary excretion) is about one-third that seen in smelters and similar settings. Arsenic compound characteristics, matrix composition, and particle size distribution probably play major roles in determining actual uptake of airborne arsenic.

  7. Arsenic Species in Chicken Breast: Temporal Variations of Metabolites, Elimination Kinetics, and Residual Concentrations.

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    Liu, Qingqing; Peng, Hanyong; Lu, Xiufen; Zuidhof, Martin J; Li, Xing-Fang; Le, X Chris

    2016-08-01

    Chicken meat has the highest per capita consumption among all meat types in North America. The practice of feeding 3-nitro-4-hydroxyphenylarsonic acid (Roxarsone, Rox) to chickens lasted for more than 60 years. However, the fate of Rox and arsenic metabolites remaining in chicken are poorly understood. We aimed to determine the elimination of Rox and metabolites from chickens and quantify the remaining arsenic species in chicken meat, providing necessary information for meaningful exposure assessment. We have conducted a 35-day feeding experiment involving 1,600 chickens, of which half were control and the other half were fed a Rox-supplemented diet for the first 28 days and then a Rox-free diet for the final 7 days. We quantified the concentrations of individual arsenic species in the breast meat of 229 chickens. Rox, arsenobetaine, arsenite, monomethylarsonic acid, dimethylarsinic acid, and a new arsenic metabolite, were detected in breast meat from chickens fed Rox. The concentrations of arsenic species, except arsenobetaine, were significantly higher in the Rox-fed than in the control chickens. The half-lives of elimination of these arsenic species were 0.4-1 day. Seven days after termination of Rox feeding, the concentrations of arsenite (3.1 μg/kg), Rox (0.4 μg/kg), and a new arsenic metabolite (0.8 μg/kg) were significantly higher in the Rox-fed chickens than in the control. Feeding of Rox to chickens increased the concentrations of five arsenic species in breast meat. Although most arsenic species were excreted rapidly when the feeding of Rox stopped, arsenic species remaining in the Rox-fed chickens were higher than the background levels. Liu Q, Peng H, Lu X, Zuidhof MJ, Li XF, Le XC. 2016. Arsenic species in chicken breast: temporal variations of metabolites, elimination kinetics, and residual concentrations. Environ Health Perspect 124:1174-1181; http://dx.doi.org/10.1289/ehp.1510530.

  8. HPLC-HG-AFS determination of arsenic species in acute promyelocytic leukemia (APL) plasma and blood cells.

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    Guo, Meihua; Wang, Wenjing; Hai, Xin; Zhou, Jin

    2017-10-25

    Arsenic trioxide (ATO) has been successfully used in the treatment of acute promyelocytic leukemia (APL). To clarify the arsenic species in APL patients, high performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS) and HG-AFS methods were developed and validated to quantify the plasma concentrations of inorganic arsenic (As(III) and As(V)) and methylated metabolites (MMA and DMA), and the total amounts of arsenic in blood cells and plasma. Blood cells and plasma were digested with mixtures of HNO 3 H 2 O 2 and analyzed by HG-AFS. For arsenic speciation, plasma samples were prepared with perchloric acid to precipitate protein. The supernatant was separated on an anion-exchange column within 6min with isocratic elution using 13mM CH 3 COONa, 3mM NaH 2 PO 4 , 4mM KNO 3 and 0.2mM EDTA-2Na. The methods provided linearity range of 0.2-20ng/mL for total arsenic and 2.0-50ng/mL for four arsenic species. The developed methods for total arsenic and arsenic species determination were precise and accurate. The spiked recoveries ranged from 81.2%-108.6% and the coefficients of variation for intra- and inter-batch precision were less than 9.3% and 12.5%, respectively. The developed methods were applied successfully for the assay of total arsenic and arsenic species in 5 APL patients. The HPLC-HG-AFS may be a good alternative for arsenic species determination in APL patients with its simplicity and low-cost in comparison with HPLC-ICP-MS. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Arsenic Metabolites, Including N-Acetyl-4-hydroxy-m-arsanilic Acid, in Chicken Litter from a Roxarsone-Feeding Study Involving 1600 Chickens.

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    Yang, Zonglin; Peng, Hanyong; Lu, Xiufen; Liu, Qingqing; Huang, Rongfu; Hu, Bin; Kachanoski, Gary; Zuidhof, Martin J; Le, X Chris

    2016-07-05

    The poultry industry has used organoarsenicals, such as 3-nitro-4-hydroxyphenylarsonic acid (Roxarsone, ROX), to prevent disease and to promote growth. Although previous studies have analyzed arsenic species in chicken litter after composting or after application to agricultural lands, it is not clear what arsenic species were excreted by chickens before biotransformation of arsenic species during composting. We describe here the identification and quantitation of arsenic species in chicken litter repeatedly collected on days 14, 24, 28, 30, and 35 of a Roxarsone-feeding study involving 1600 chickens of two strains. High performance liquid chromatography separation with simultaneous detection by both inductively coupled plasma mass spectrometry and electrospray ionization tandem mass spectrometry provided complementary information necessary for the identification and quantitation of arsenic species. A new metabolite, N-acetyl-4-hydroxy-m-arsanilic acid (N-AHAA), was identified, and it accounted for 3-12% of total arsenic. Speciation analyses of litter samples collected from ROX-fed chickens on days 14, 24, 28, 30, and 35 showed the presence of N-AHAA, 3-amino-4-hydroxyphenylarsonic acid (3-AHPAA), inorganic arsenite (As(III)), arsenate (As(V)), monomethylarsonic acid (MMA(V)), dimethylarsinic acid (DMA(V)), and ROX. 3-AHPAA accounted for 3-19% of the total arsenic. Inorganic arsenicals (the sum of As(III) and As(V)) comprised 2-6% (mean 3.5%) of total arsenic. Our results on the detection of inorganic arsenicals, methylarsenicals, 3-AHPAA, and N-AHAA in the chicken litter support recent findings that ROX is actually metabolized by the chicken or its gut microbiome. The presence of the toxic metabolites in chicken litter is environmentally relevant as chicken litter is commonly used as fertilizer.

  10. Effects of endogenous hydrogen peroxide and glutathione on the stability of arsenic metabolites in rat bile

    International Nuclear Information System (INIS)

    Kobayashi, Yayoi; Hirano, Seishiro

    2008-01-01

    Trivalent arsenicals such as arsenite (iAs III ), monomethylarsonous acid (MMA III ) and dimethylarsinous acid (DMA III ) are more toxic than analogous pentavalent compounds such as arsenate (iAs V ), monomethylarsonic acid (MMA V ) and dimethylarsinic acid (DMA V ). It has been reported that arsenic-glutathione (As-GSH) complexes such as arsenic triglutathione (ATG) and methylarsenic diglutathione (MADG) are major metabolites in rat bile following intravenous administration of iAs III . Recently, we have shown that both ATG and MADG are unstable and easily hydrolyzed to iAs III and MMA III , respectively, and that MMA III is oxidized to MMA V in bile. In the present study we report the effects of H 2 O 2 and GSH on the stability of As-GSH complexes in rat bile. Male SD rats were injected intravenously with saline or iAs III at a dose of 0.2 or 2.0 mg As/kg body weight, and bile fluid was collected on ice for 30 min. To estimate the stability of As-GSH complexes in bile, ATG or MADG was added to untreated, heat-treated, catalase-treated, or dialyzed bile, and then incubated at 37 deg. C for 10 min. Concentrations of biliary H 2 O 2 and GSH in the higher dose group were 12.6- and 4.5-times higher than the control value, respectively. Exogenously added trivalent arsenicals were oxidized to pentavalent arsenicals in the bile depending on the biliary concentration of H 2 O 2 . Both catalase and dialysis prevented oxidation of trivalent arsenicals to the corresponding pentavalent compounds. Exogenously added GSH stabilized As-GSH complexes in bile. These results suggest that H 2 O 2 converts trivalent arsenicals to less toxic pentavalent arsenicals, whereas GSH prevents hydrolysis of As-GSH complexes and the generation of unconjugated toxic trivalent arsenicals

  11. Differences in Urinary Arsenic Metabolites between Diabetic and Non-Diabetic Subjects in Bangladesh

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    Tamie Nakajima

    2013-03-01

    Full Text Available Ingestion of inorganic arsenic (iAs is considered to be related to the development of diabetes mellitus. In order to clarify the possible differences in the metabolism in diabetics, we measured urinary iAs metabolites in diabetic cases and non-diabetic control subjects in Faridpur, an arsenic-contaminated area in Bangladesh. Physician-diagnosed type 2 diabetic cases (140 persons and non-diabetic controls (180 persons were recruited. Drinking water and spot urine samples were collected. Mean concentrations of total arsenic in drinking water did not differ between cases (85.1 μg/L and controls (85.8 μg/L. The percentage of urinary iAs (iAs% was significantly lower in cases (8.6% than in controls (10.4%, while that of dimethylarsinic acid (DMA% was higher in cases (82.6% than in controls (79.9%. This may have been due to the higher secondary methylation index (SMI in the former (11.6 rather than the latter (10.0. Adjusting for matching factors (sex and unions, and the additional other covariates (age and water arsenic significantly attenuated the differences in iAs%, SMI, and DMA%, respectively, though the difference in monomethylarsonic acid% was newly significant in the latter adjustment. Our study did not suggest any significant differences in urinary arsenic metabolites between diabetic and non-diabetic subjects.

  12. Distribution and Excretion of Arsenic Metabolites after Oral Administration of Seafood-Related Organoarsenicals in Rats

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    Yayoi Kobayashi

    2016-09-01

    Full Text Available Less information is available on the metabolism of organic arsenicals compared to inorganic arsenic in mammals. In the present study, we investigated tissue distribution, metabolism and excretion in rats of organoarsenicals, dimethylarsinic acid (DMAV, arsenobetaine (AB, arsenocholine (AC and trimethylarsine oxide (TMAOV. Among these animals, arsenic concentrations in red blood cells (RBCs and spleen increased remarkably only in the DMAV group. Hepatic arsenic concentration increased significantly only in the AC group. Approximately 17%, 72% and 60% of the dose was excreted in urine in two days in the DMAV, AB and AC groups, respectively; virtually the entire dose was excreted in urine in one day in the TMAOV group. On the other hand, approximately 18%, 0.2%, 0.5% and 0.1% of the dose was excreted in feces in two days in the DMAV, AB, AC and TMAOV groups, respectively. A large amount of arsenic was accumulated in RBCs in the form of protein-bound dimethylarsinous acid (DMAIII, and dimethylmonothioarsinic acid (DMMTAV, a reportedly toxic thio-arsenical, was found in urine and fecal extract in the DMAV group. These results suggest that intake of DMAV is a potential health hazard, given that the metabolites of DMAV, such as DMAIII and DMMTAV, are known to be highly toxic.

  13. Low selenium status affects arsenic metabolites in an arsenic exposed population with skin lesions.

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    Huang, Zhi; Pei, Qiuling; Sun, Guifan; Zhang, Sichum; Liang, Jiang; Gao, Yi; Zhang, Xinrong

    2008-01-01

    The antagonistic effects between selenium (Se) and arsenic (As) suggest that low selenium status plays important roles in arsenism development. However, no study has been reported for humans suffering from chronic arsenic exposure with low selenium status. Sixty-three subjects were divided into 2 experimental groups by skin lesions (including hyperkeratosis, depigmentation, and hyperpigmentation). Total urine and serum concentrations of arsenic and selenium were determined by ICP-MS with collision/reaction cell. Arsenic species were analysed by ICP-MS coupled with HPLC. The mean concentration of As in the drinking waters was 41.5 microg/l. The selenium dietary intake for the studied population was 31.7 microg Se/d, and which for the cases and controls were 25.9 and 36.3 microg Se/d, respectively. Compared with the controls, the skin lesions cases had lower selenium concentrations in serum and urine (41.4 vs 49.6 microg/l and 71.0 vs 78.8 microg/l, respectively), higher inorganic arsenic (iAs) in serum (5.2 vs 3.4 microg/l, PiAs in serum and urine (20.2) vs 16.9% and 18.3 vs 14.5%, respectively, PiAs and its inhibition to be biotransformed to DMA occurred in human due to chronic exposure of low selenium status.

  14. Relationship of urinary arsenic metabolites to intake estimates in residents of the Red River Delta, Vietnam

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    Agusa, Tetsuro; Kunito, Takashi; Minh, Tu Binh; Pham Thi Kim Trang; Iwata, Hisato; Pham Hung Viet; Tanabe, Shinsuke

    2009-01-01

    This study investigated the status of arsenic (As) exposure from groundwater and rice, and its methylation capacity in residents from the Red River Delta, Vietnam. Arsenic levels in groundwater ranged from <1.8 to 486 μg/L. Remarkably, 86% of groundwater samples exceeded WHO drinking water guideline of 10 μg/L. Also, estimated inorganic As intake from groundwater and rice were over Provisional Tolerable Weekly Intake (15 μg/week/kg body wt.) by FAO/WHO for 92% of the residents examined. Inorganic As and its metabolite (monomethylarsonic acid and dimethylarsinic acid) concentrations in human urine were positively correlated with estimated inorganic As intake. These results suggest that residents in these areas are exposed to As through consumption of groundwater and rice, and potential health risk of As is of great concern for these people. Urinary concentration ratios of dimethylarsinic acid to monomethylarsonic acid in children were higher than those in adults, especially among men, indicating greater As methylation capacity in children. - Positive correlations between estimated arsenic intake and urinary inorganic arsenic and its metabolites were observed in human from the Red River Delta, Vietnam

  15. Relationship of urinary arsenic metabolites to intake estimates in residents of the Red River Delta, Vietnam

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    Agusa, Tetsuro [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Department of Legal Medicine, Shimane University Faculty of Medicine, Enya 89-1, Izumo 693-8501 (Japan); Kunito, Takashi [Department of Environmental Sciences, Faculty of Science, Shinshu University, 3-1-1 Asahi, Matsumoto 390-8621 (Japan); Minh, Tu Binh [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Department of Biology and Chemistry (BCH), City University of Hong Kong, 83 Tat Chee Avenue, Kowloon Tong, Hong Kong (China); Pham Thi Kim Trang [Center for Environmental Technology and Sustainable Development (CETASD), Hanoi National University, 334 Nguyen Trai Street, Thanh Xuan, Hanoi (Viet Nam); Iwata, Hisato [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Pham Hung Viet [Center for Environmental Technology and Sustainable Development (CETASD), Hanoi National University, 334 Nguyen Trai Street, Thanh Xuan, Hanoi (Viet Nam); Tanabe, Shinsuke [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan)], E-mail: shinsuke@agr.ehime-u.ac.jp

    2009-02-15

    This study investigated the status of arsenic (As) exposure from groundwater and rice, and its methylation capacity in residents from the Red River Delta, Vietnam. Arsenic levels in groundwater ranged from <1.8 to 486 {mu}g/L. Remarkably, 86% of groundwater samples exceeded WHO drinking water guideline of 10 {mu}g/L. Also, estimated inorganic As intake from groundwater and rice were over Provisional Tolerable Weekly Intake (15 {mu}g/week/kg body wt.) by FAO/WHO for 92% of the residents examined. Inorganic As and its metabolite (monomethylarsonic acid and dimethylarsinic acid) concentrations in human urine were positively correlated with estimated inorganic As intake. These results suggest that residents in these areas are exposed to As through consumption of groundwater and rice, and potential health risk of As is of great concern for these people. Urinary concentration ratios of dimethylarsinic acid to monomethylarsonic acid in children were higher than those in adults, especially among men, indicating greater As methylation capacity in children. - Positive correlations between estimated arsenic intake and urinary inorganic arsenic and its metabolites were observed in human from the Red River Delta, Vietnam.

  16. Levels of infants' urinary arsenic metabolites related to formula feeding and weaning with rice products exceeding the EU inorganic arsenic standard.

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    Antonio J Signes-Pastor

    Full Text Available Early childhood inorganic arsenic (i-As exposure is of particular concern since it may adversely impact on lifetime health outcomes. Infants' urinary arsenic (As metabolites were analysed in 79 infants by inductively coupled plasma-mass spectrometric detection (IC-ICP-MS to evaluate i-As exposure pre- and post-weaning. Levels of i-As in rice-based weaning and infants' foods were also determined to relate to urinary As levels. Higher As levels, especially of monomethylarsonic acid (MMA and dimethylarsinic acid (DMA, were found in urine from formula fed infants compared to those breastfed. Urine from infants post-weaning consuming rice-products resulted in higher urinary MMA and DMA compared to the paired pre-weaning urine samples. The European Union (EU has regulated i-As in rice since 1st January 2016. Comparing infants' rice-based foods before and after this date, little change was found. Nearly ¾ of the rice-based products specifically marketed for infants and young children contained i-As over the 0.1 mg/kg EU limit. Efforts should be made to provide low i-As rice and rice-based products consumed by infants and young children that do not exceed the maximum i-As level to protect this vulnerable subpopulation.

  17. Arsenate impact on the metabolite profile, production and arsenic loading of xylem sap in cucumbers (Cucumis sativus L.

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    Kalle eUroic

    2012-04-01

    Full Text Available Arsenic uptake and translocation studies on xylem sap focus generally on the concentration and speciation of arsenic in the xylem. Arsenic impact on the xylem sap metabolite profile and its production during short term exposure has not been reported in detail. To investigate this, cucumbers were grown hydroponically and arsenate (AsV and DMA were used for plant treatment for 24 h. Total arsenic and arsenic speciation in xylem sap was analysed including a metabolite profiling under arsenate stress. Produced xylem sap was quantified and absolute arsenic transported was determined. AsV exposure has a significant impact on the metabolite profile of xylem sap. Four m/z values corresponding to four compounds were up regulated, one compound down regulated by arsenate exposure. The compound down regulated was identified to be isoleucine. Furthermore, arsenate has a significant influence on sap production, leading to a reduction of up to 96 % sap production when plants are exposed to 1000 μg kg-1 arsenate. No difference to control plants was observed when plants were exposed to 1000 μg kg-1 DMA. Absolute arsenic amount in xylem sap was the lowest at high arsenate exposure. These results show that AsV has a significant impact on the production and metabolite profile of xylem sap. The physiological importance of isoleucine needs further attention.

  18. Arsenate Impact on the Metabolite Profile, Production, and Arsenic Loading of Xylem Sap in Cucumbers (Cucumis sativus L.)

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    Uroic, M. Kalle; Salaün, Pascal; Raab, Andrea; Feldmann, Jörg

    2012-01-01

    Arsenic uptake and translocation studies on xylem sap focus generally on the concentration and speciation of arsenic in the xylem. Arsenic impact on the xylem sap metabolite profile and its production during short term exposure has not been reported in detail. To investigate this, cucumbers were grown hydroponically and arsenate (AsV) and DMA were used for plant treatment for 24 h. Total arsenic and arsenic speciation in xylem sap was analyzed including a metabolite profiling under AsV stress. Produced xylem sap was quantified and absolute arsenic transported was determined. AsV exposure had a significant impact on the metabolite profile of xylem sap. Four m/z values corresponding to four compounds were up-regulated, one compound down-regulated by AsV exposure. The compound down-regulated was identified to be isoleucine. Furthermore, AsV exposure had a significant influence on sap production, leading to a reduction of up to 96% sap production when plants were exposed to 1000 μg kg−1 AsV. No difference to control plants was observed when plants were exposed to 1000 μg kg−1 DMA. Absolute arsenic amount in xylem sap was the lowest at high AsV exposure. These results show that AsV has a significant impact on the production and metabolite profile of xylem sap. The physiological importance of isoleucine needs further attention. PMID:22536187

  19. Carbon-enhanced inductively coupled plasma mass spectrometric detection of arsenic and selenium and its application to arsenic speciation

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    Larsen, Erik Huusfeldt; Sturup, Stefan

    1994-01-01

    Addition of carbon as methanol or ammonium carbonate to the aqueous analyte solutions in combination with increased plasma power input enhanced the inductively coupled plasma mass spectrometry (ICP-MS) signal intensities of arsenic and selenium. In the presence of the optimum 3% v/v methanol...... (noise) was not increased. Therefore, the observed increase in analyte sensitivity led to a similar increase in signal-to-noise ratio. The addition of carbon as ammonium carbonate enhanced the arsenic signal by a similar factor but caused severe contamination of the ICP-MS instrument by carbon. In the 3....../nebulization efficiency. It is proposed that an increased population of carbon ions or carbon-containing ions in the plasma facilitates a more complete ionization of analytes lower in ionization energy than carbon itself. The enhanced detection power for arsenic was applied to arsenic speciation by high...

  20. Thio-dimethylarsinate is a common metabolite in urine samples from arsenic-exposed women in Bangladesh

    International Nuclear Information System (INIS)

    Raml, Reingard; Rumpler, Alice; Goessler, Walter; Vahter, Marie; Li Li; Ochi, Takafumi; Francesconi, Kevin A.

    2007-01-01

    Over the last 6 years, much work on arsenic species in urine samples has been directed toward the determination of the reduced dimethylated arsenic species, DMA(III), because of its high toxicity and perceived key role in the metabolism of inorganic arsenic. Recent work, however, has suggested that DMA(III) may at times have been misidentified because its chromatographic properties can be similar to those of thio-dimethylarsinate (thio-DMA). We analyzed by HPLC-ICPMS (inductively coupled plasma mass spectrometry) urine samples from 75 arsenic-exposed women from Bangladesh with total arsenic concentrations ranging from 8 to 1034 μg As/L and found that thio-DMA was present in 44% of the samples at concentrations ranging mostly from trace amounts to 24 μg As/L (one sample contained 123 μg As/L). Cytotoxicity testing with HepG2 cells derived from human hepatocarcinoma indicated that thio-DMA was about 10-fold more cytotoxic than dimethylarsinate (DMA). The widespread occurrence of thio-DMA in urine from these arsenic-exposed women suggests that this arsenical may also be present in other urine samples and has so far escaped detection. The work highlights the need for analytical methods providing specific determinations of arsenic compounds in future studies on arsenic metabolism and toxicology

  1. Thio-dimethylarsinate is a common metabolite in urine samples from arsenic-exposed women in Bangladesh

    Energy Technology Data Exchange (ETDEWEB)

    Raml, Reingard; Rumpler, Alice; Goessler, Walter [Karl-Franzens University Graz, Institute of Chemistry-Analytical Chemistry, Universitaetsplatz 1, 8010 Graz (Austria); Vahter, Marie; Li, Li [Institute of Environmental Medicine, Karolinska Institutet, PO Box 210, 17177 Stockholm (Sweden); Ochi, Takafumi [Laboratory of Toxicology, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195 (Japan); Francesconi, Kevin A. [Karl-Franzens University Graz, Institute of Chemistry-Analytical Chemistry, Universitaetsplatz 1, 8010 Graz (Austria)], E-mail: kevin.francesconi@uni-graz.at

    2007-08-01

    Over the last 6 years, much work on arsenic species in urine samples has been directed toward the determination of the reduced dimethylated arsenic species, DMA(III), because of its high toxicity and perceived key role in the metabolism of inorganic arsenic. Recent work, however, has suggested that DMA(III) may at times have been misidentified because its chromatographic properties can be similar to those of thio-dimethylarsinate (thio-DMA). We analyzed by HPLC-ICPMS (inductively coupled plasma mass spectrometry) urine samples from 75 arsenic-exposed women from Bangladesh with total arsenic concentrations ranging from 8 to 1034 {mu}g As/L and found that thio-DMA was present in 44% of the samples at concentrations ranging mostly from trace amounts to 24 {mu}g As/L (one sample contained 123 {mu}g As/L). Cytotoxicity testing with HepG2 cells derived from human hepatocarcinoma indicated that thio-DMA was about 10-fold more cytotoxic than dimethylarsinate (DMA). The widespread occurrence of thio-DMA in urine from these arsenic-exposed women suggests that this arsenical may also be present in other urine samples and has so far escaped detection. The work highlights the need for analytical methods providing specific determinations of arsenic compounds in future studies on arsenic metabolism and toxicology.

  2. TISSUE DISTRIBUTION OF INORGANIC ARSENIC (AS) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (ASV)

    Science.gov (United States)

    TISSUE DISTRIBUTION OF INORGANIC ARSENIC (iAs) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (AsV). E M Kenyon1, L M Del Razo2, and M F Hughes1. 1NHEERL, ORD, US EPA, RTP, NC, USA; 2CINVESTAV-IPN, Mexico City, Mexico.The relationship o...

  3. Clozapine response and plasma catecholamines and their metabolites.

    Science.gov (United States)

    Green, A I; Alam, M Y; Sobieraj, J T; Pappalardo, K M; Waternaux, C; Salzman, C; Schatzberg, A F; Schildkraut, J J

    1993-02-01

    The atypical neuroleptic clozapine has an unusual profile of clinical effects and a distinctive spectrum of pharmacological actions. Plasma measures of catecholamines and their metabolites have been used in the past to study the action of typical neuroleptics. We obtained longitudinal assessments of plasma measures of dopamine (pDA), norepinephrine (pNE), and their metabolites, homovanillic acid (pHVA) and 3-methoxy-4-hydroxyphenylglycol (pMHPG), in eight treatment-resistant or treatment-intolerant schizophrenic patients who were treated with clozapine for 12 weeks following a prolonged drug-washout period. Our findings from the study of these eight patients suggest the following: Plasma levels of HVA and possibly NE derived from the neuroleptic-free baseline period may predict response to clozapine; plasma levels of HVA and MHPG decrease during the initial weeks of treatment in responders but not in nonresponders; and plasma levels of DA and NE increase in both responders and nonresponders to clozapine.

  4. Identification of drug metabolites in human plasma or serum integrating metabolite prediction, LC-HRMS and untargeted data processing

    NARCIS (Netherlands)

    Jacobs, P.L.; Ridder, L.; Ruijken, M.; Rosing, H.; Jager, N.G.L.; Beijnen, J.H.; Bas, R.R.; Dongen, W.D. van

    2013-01-01

    Background: Comprehensive identification of human drug metabolites in first-in-man studies is crucial to avoid delays in later stages of drug development. We developed an efficient workflow for systematic identification of human metabolites in plasma or serum that combines metabolite prediction,

  5. HPLC analysis of prostaglandin metabolites plasma from irradiated rats

    International Nuclear Information System (INIS)

    Walden, T.L. Jr.; Catravas, G.N.

    1985-01-01

    The authors used RP-HPLC to quantitatively and qualitatively evaluate the PG metabolites in the plasma of rats during the first 24 hrs following a 10 Gy whole body dose of cobalt 60 gamma rays. The PGs and other arachidonic acid metabolites in plasma were extracted and then covalently attached to a fluroescent dye to enhance detection. A number of PGs and their metabolites were observed in the irradiated sample, including: 13,14 dihydro -15 keto PGE/sub 2/ and 13,14, dihydro -15 keto PGF/sub 2/, and their respective precursors, PGE/sub 2/ and PGF/sub 2/. The two major compounds present in the plasma samples were 13,14 dihydro -15 keto PFG/sub 2/ and another compound which is as yet unidentified. The levels of the individual PGs within a sample varied with time after irradiation, and the time at which a PG reached a peak level in the plasma depended on the particular PG in question. 13,14 dihdyro -15 keto PGD/sub 2/ was observed to reach a peak plasma concentration at 6 hours postirradiation, and at that time was at least 20 times higher than control levels

  6. Three plasma metabolite signatures for diagnosing high altitude pulmonary edema

    Science.gov (United States)

    Guo, Li; Tan, Guangguo; Liu, Ping; Li, Huijie; Tang, Lulu; Huang, Lan; Ren, Qian

    2015-10-01

    High-altitude pulmonary edema (HAPE) is a potentially fatal condition, occurring at altitudes greater than 3,000 m and affecting rapidly ascending, non-acclimatized healthy individuals. However, the lack of biomarkers for this disease still constitutes a bottleneck in the clinical diagnosis. Here, ultra-high performance liquid chromatography coupled with Q-TOF mass spectrometry was applied to study plasma metabolite profiling from 57 HAPE and 57 control subjects. 14 differential plasma metabolites responsible for the discrimination between the two groups from discovery set (35 HAPE subjects and 35 healthy controls) were identified. Furthermore, 3 of the 14 metabolites (C8-ceramide, sphingosine and glutamine) were selected as candidate diagnostic biomarkers for HAPE using metabolic pathway impact analysis. The feasibility of using the combination of these three biomarkers for HAPE was evaluated, where the area under the receiver operating characteristic curve (AUC) was 0.981 and 0.942 in the discovery set and the validation set (22 HAPE subjects and 22 healthy controls), respectively. Taken together, these results suggested that this composite plasma metabolite signature may be used in HAPE diagnosis, especially after further investigation and verification with larger samples.

  7. Determination of Arsenic in Sinus Wash and Tap Water by Inductively Coupled Plasma-Mass Spectrometry

    Science.gov (United States)

    Donnell, Anna M.; Nahan, Keaton; Holloway, Dawone; Vonderheide, Anne P.

    2016-01-01

    Arsenic is a toxic element to which humans are primarily exposed through food and water; it occurs as a result of human activities and naturally from the earth's crust. An experiment was developed for a senior level analytical laboratory utilizing an Inductively Coupled Plasma-Mass Spectrometer (ICP-MS) for the analysis of arsenic in household…

  8. Radioimmunossay of hormones and metabolites in blood serum and plasma

    International Nuclear Information System (INIS)

    Khare, G.P.

    1978-01-01

    Hormones or metabolites which are capable of producing antibodies can be detected and precisely quantitated by this method. Antibodies, to various hormones or metabolites whose assay is desired, are adsorbed onto commercially available imitation or cultured pearls. These pearls coated with antibody are contacted with a buffered reaction mixture containing blood serum or plasma specimen and respective radioactive antigen. The entire reaction is allowed to proceed for a time sufficient to form antigen (radioactive or non-radioactive)-antibody complex. These complexes on the pearls are washed and the total amount of radioactivity emanating from the complex is measured. This is indicative of the extent of binding of radioactive antigen and provides an indirect correlation of the amount of non-radioactive antigen present in the serum or plasma sample

  9. Association between arsenic exposure and plasma cholinesterase activity: a population based study in Bangladesh

    Directory of Open Access Journals (Sweden)

    Karim Md Rezaul

    2010-07-01

    Full Text Available Abstract Background Arsenic is a potent pollutant that has caused an environmental catastrophe in certain parts of the world including Bangladesh where millions of people are presently at risk due to drinking water contaminated by arsenic. Chronic arsenic exposure has been scientifically shown as a cause for liver damage, cancers, neurological disorders and several other ailments. The relationship between plasma cholinesterase (PChE activity and arsenic exposure has not yet been clearly documented. However, decreased PChE activity has been found in patients suffering liver dysfunction, heart attack, cancer metastasis and neurotoxicity. Therefore, in this study, we evaluated the PChE activity in individuals exposed to arsenic via drinking water in Bangladesh. Methods A total of 141 Bangladeshi residents living in arsenic endemic areas with the mean arsenic exposure of 14.10 ± 3.27 years were selected as study subjects and split into tertile groups based on three water arsenic concentrations: low ( 265 μg/L. Study subjects were further sub-divided into two groups (≤50 μg/L and > 50 μg/L based on the recommended upper limit of water arsenic concentration (50 μg/L in Bangladesh. Blood samples were collected from the study subjects by venipuncture and arsenic concentrations in drinking water, hair and nail samples were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS. PChE activity was assayed by spectrophotometer. Results Arsenic concentrations in hair and nails were positively correlated with the arsenic levels in drinking water. Significant decreases in PChE activity were observed with increasing concentrations of arsenic in water, hair and nails. The average levels of PChE activity in low, medium and high arsenic exposure groups were also significantly different between each group. Lower levels of PChE activity were also observed in the > 50 μg/L group compared to the ≤50 μg/L group. Moreover, PChE activity was

  10. Associations between Methylated Metabolites of Arsenic and Selenium in Urine of Pregnant Bangladeshi Women and Interactions between the Main Genes Involved.

    Science.gov (United States)

    Skröder, Helena; Engström, Karin; Kuehnelt, Doris; Kippler, Maria; Francesconi, Kevin; Nermell, Barbro; Tofail, Fahmida; Broberg, Karin; Vahter, Marie

    2018-02-01

    It has been proposed that interactions between selenium and arsenic in the body may affect their kinetics and toxicity. However, it is unknown how the elements influence each other in humans. We aimed to investigate potential interactions in the methylation of selenium and arsenic. Urinary selenium (U-Se) and arsenic (U-As) were measured using inductively coupled plasma mass spectrometry (ICPMS) in samples collected from pregnant women ( n =226) in rural Bangladesh at gestational weeks (GW) 8, 14, 19, and 30. Urinary concentrations of trimethyl selenonium ion (TMSe) were measured by HPLC-vapor generation-ICPMS, as were inorganic arsenic (iAs), methylarsonic acid (MMA), and dimethylarsinic acid (DMA). Methylation efficiency was assessed based on relative amounts (%) of arsenic and selenium metabolites in urine. Genotyping for the main arsenite and selenium methyltransferases, AS3MT and INMT, was performed using TaqMan probes or Sequenom. Multivariable-adjusted linear regression analyses indicated that %TMSe (at GW8) was positively associated with %MMA (β=1.3, 95% CI: 0.56, 2.0) and U-As, and inversely associated with %DMA and U-Se in producers of TMSe ( INMT rs6970396 AG+AA, n =74), who had a wide range of urinary TMSe (12-42%). Also, %TMSe decreased in parallel to %MMA during pregnancy, especially in the first trimester (-0.58 %TMSe per gestational week). We found a gene-gene interaction for %MMA ( p -interaction=0.076 for haplotype 1). In analysis stratified by INMT genotype, the association between %MMA and both AS3MT haplotypes 1 and 3 was stronger in women with the INMT GG (TMSe nonproducers, 5th-95th percentile: 0.2-2%TMSe) vs. AG+AA genotype. Our findings for Bangladeshi women suggest a positive association between urinary %MMA and %TMSe. Genes involved in the methylation of selenium and arsenic may interact on associations with urinary %MMA. https://doi.org/10.1289/EHP1912.

  11. [Purification of arsenic-binding proteins in hamster plasma after oral administration of arsenite].

    Science.gov (United States)

    Wang, Wenwen; Zhang, Min; Li, Chunhui; Qin, Yingjie; Hua, Naranmandura

    2013-01-01

    To purify the arsenic-binding proteins (As-BP) in hamster plasma after a single oral administration of arsenite (iAs(III)). Arsenite was given to hamsters in a single dose. Three types of HPLC columns, size exclusion, gel filtration and anion exchange columns, combined with an inductively coupled argon plasma mass spectrometer (ICP MS) were used to purify the As-BP in hamster plasma. SDS-PAGE was used to confirm the arsenic-binding proteins at each purification step. The three-step purification process successfully separated As-BP from other proteins (ie, arsenic unbound proteins) in hamster plasma. The molecular mass of purified As-BP in plasma was approximately 40-50 kD on SDS-PAGE. The three-step purification method is a simple and fast approach to purify the As-BP in plasma samples.

  12. Blood sampling and hemolysis affect concentration of plasma metabolites

    DEFF Research Database (Denmark)

    Theil, Peter Kappel; Pedersen, Lene Juul; Jensen, Margit Bak

    2012-01-01

    design and blood was collected after restraint via vein puncture 1, 4, 11, and 23 h after morning feeding. Plasma samples were categorized as without or with minor or major hemolysis [clear (n = 218), yellow (n = 97), or red (n = 37)] upon centrifugation. Plasma NEFA (P ...Two experiments were carried out to reveal and quantify plasma metabolites that are sensitive to hemolysis and animal stress due to the blood sampling procedure (vein puncture vs. catheter). In Exp. 1, 48 sows were fed 4 diets either once (0800 h) or twice daily (0800 h and 1500 h) in a crossover......, a subset of samples from 24 sows fed twice daily in Exp. 1 was combined with data obtained from 30 sows sampled using jugular vein catheters. All sows in Exp. 2 were fed twice daily (0800 h and 1500 h) and blood samples collected repeatedly 1, 4, 11, and 23 h after morning feeding (other conditions were...

  13. Arsenic

    Science.gov (United States)

    ... for drinking-water quality Chemical hazards in drinking-water: arsenic Evaluations of the Joint FAO/WHO Expert Committee ... Africa Americas South-East Asia Europe Eastern Mediterranean Western ...

  14. Mouse arsenic (+3 oxidation state) methyltransferase genotype affects metabolism and tissue dosimetry of arsenicals after arsenite administration in drinking water.

    Science.gov (United States)

    Chen, Baowei; Arnold, Lora L; Cohen, Samuel M; Thomas, David J; Le, X Chris

    2011-12-01

    Arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes methylation of inorganic arsenic (iAs) producing a number of methylated arsenic metabolites. Although methylation has been commonly considered a pathway for detoxification of arsenic, some highly reactive methylated arsenicals may contribute to toxicity associated with exposure to inorganic arsenic. Here, adult female wild-type (WT) C57BL/6 mice and female As3mt knockout (KO) mice received drinking water that contained 1, 10, or 25 ppm (mg/l) of arsenite for 33 days and blood, liver, kidney, and lung were taken for arsenic speciation. Genotype markedly affected concentrations of arsenicals in tissues. Summed concentrations of arsenicals in plasma were higher in WT than in KO mice; in red blood cells, summed concentrations of arsenicals were higher in KO than in WT mice. In liver, kidney, and lung, summed concentrations of arsenicals were greater in KO than in WT mice. Although capacity for arsenic methylation is much reduced in KO mice, some mono-, di-, and tri-methylated arsenicals were found in tissues of KO mice, likely reflecting the activity of other tissue methyltransferases or preabsorptive metabolism by the microbiota of the gastrointestinal tract. These results show that the genotype for arsenic methylation determines the phenotypes of arsenic retention and distribution and affects the dose- and organ-dependent toxicity associated with exposure to inorganic arsenic.

  15. Levels of plasma selenium and urinary total arsenic interact to affect the risk for prostate cancer.

    Science.gov (United States)

    Hsueh, Yu-Mei; Su, Chien-Tien; Shiue, Horng-Sheng; Chen, Wei-Jen; Pu, Yeong-Shiau; Lin, Ying-Chin; Tsai, Cheng-Shiuan; Huang, Chao-Yuan

    2017-09-01

    This study investigated whether plasma selenium levels modified the risk for prostate cancer (PC) related to arsenic exposure. We conducted a case-control study that included 318 PC patients and 318 age-matched, healthy control subjects. Urinary arsenic profiles were examined using HPLC-HG-AAS and plasma selenium levels were measured by ICP-MS. We found that plasma selenium levels displayed a significant dose-dependent inverse association with PC. The odds ratio (OR) and 95% confidence interval (CI) for PC was 0.07 (0.04-0.13) among participants with a plasma selenium level >28.06 μg/dL vs. ≤19.13 μg/dL. A multivariate analysis showed that participants with a urinary total arsenic concentration >29.28 μg/L had a significantly higher OR (1.75, 1.06-2.89) for PC than participants with ≤29.89 μg/L. The combined presence of a low plasma selenium level and a high urinary total arsenic concentration exponentially increased the OR for PC, and additively interacted with PSA at levels ≥20 ng/mL. This is the first epidemiological study to examine the combined effects of plasma selenium and urinary total arsenic levels on the OR for PC. Our data suggest a low plasma selenium level coupled with a high urinary total arsenic concentration creates a significant risk for aggressive PC. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Ultra-Sensitive Elemental Analysis Using Plasmas 5.Speciation of Arsenic Compounds in Biological Samples by High Performance Liquid Chromatography-Inductively Coupled Plasma Mass Spectrometry System

    Science.gov (United States)

    Kaise, Toshikazu

    Arsenic originating from the lithosphere is widely distributed in the environment. Many arsenicals in the environment are in organic and methylated species. These arsenic compounds in drinking water or food products of marine origin are absorbed in human digestive tracts, metabolized in the human body, and excreted viatheurine. Because arsenic shows varying biological a spects depending on its chemical species, the biological characteristics of arsenic must be determined. It is thought that some metabolic pathways for arsenic and some arsenic circulation exist in aqueous ecosystems. In this paper, the current status of the speciation analysis of arsenic by HPLC/ICP-MS (High Performance Liquid Chromatography-Inductively Coupled Plasma Mass spectrometry) in environmental and biological samples is summarized using recent data.

  17. Association Between Variants in Arsenic (+3 Oxidation State) Methyltranserase (AS3MT) and Urinary Metabolites of Inorganic Arsenic: Role of Exposure Level

    Science.gov (United States)

    Xu, Xiaofan; Drobná, Zuzana; Voruganti, V. Saroja; Barron, Keri; González-Horta, Carmen; Sánchez-Ramírez, Blanca; Ballinas-Casarrubias, Lourdes; Cerón, Roberto Hernández; Morales, Damián Viniegra; Terrazas, Francisco A. Baeza; Ishida, María C.; Gutiérrez-Torres, Daniela S.; Saunders, R. Jesse; Crandell, Jamie; Fry, Rebecca C.; Loomis, Dana; García-Vargas, Gonzalo G.; Del Razo, Luz M.; Stýblo, Miroslav; Mendez, Michelle A.

    2016-01-01

    Abstract Variants in AS3MT, the gene encoding arsenic (+3 oxidation state) methyltranserase, have been shown to influence patterns of inorganic arsenic (iAs) metabolism. Several studies have suggested that capacity to metabolize iAs may vary depending on levels of iAs exposure. However, it is not known whether the influence of variants in AS3MT on iAs metabolism also vary by level of exposure. We investigated, in a population of Mexican adults exposed to drinking water As, whether associations between 7 candidate variants in AS3MT and urinary iAs metabolites were consistent with prior studies, and whether these associations varied depending on the level of exposure. Overall, associations between urinary iAs metabolites and AS3MT variants were consistent with the literature. Referent genotypes, defined as the genotype previously associated with a higher percentage of urinary dimethylated As (DMAs%), were associated with significant increases in the DMAs% and ratio of DMAs to monomethylated As (MAs), and significant reductions in MAs% and iAs%. For 3 variants, associations between genotypes and iAs metabolism were significantly stronger among subjects exposed to water As >50 versus ≤50 ppb (water As X genotype interaction P iAs exposure may influence the extent to which several AS3MT variants affect iAs metabolism. The variants most strongly associated with iAs metabolism—and perhaps with susceptibility to iAs-associated disease—may vary in settings with exposure level. PMID:27370415

  18. Protective effects of plasma alpha-tocopherols on the risk of inorganic arsenic-related urothelial carcinoma

    International Nuclear Information System (INIS)

    Chung, Chi-Jung; Pu, Yeong-Shiau; Chen, Ying-Ting; Su, Chien-Tien; Wu, Chia-Chang; Shiue, Horng-Sheng; Huang, Chao-Yuan; Hsueh, Yu-Mei

    2011-01-01

    Arsenic plays an important role in producing oxidative stress in cultured cells. To investigate the interaction between high oxidative stress and low arsenic methylation capacity on arsenic carcinogenesis, a case-control study was conducted to evaluate the relationship among the indices of oxidative stress, such as urinary 8-hydroxydeoxyquanine (8-OHdG), as well as plasma micronutrients and urinary arsenic profiles on urothelial carcinoma (UC) risk. Urinary 8-OHdG was measured using high-sensitivity enzyme-linked immunosorbent assay kits. The urinary arsenic species were analyzed using high-performance liquid chromatography and hydride generator-atomic absorption spectrometry. Plasma micronutrient levels were analyzed using reversed-phase high-performance liquid chromatography. The present study showed a significant protective effect of plasma alpha-tocopherol on UC risk. Plasma alpha-tocopherol levels were significantly inversely related to urinary total arsenic concentrations and inorganic arsenic percentage (InAs%), and significantly positively related to dimethylarsinic acid percentage (DMA%). There were no correlations between plasma micronutrients and urinary 8-OHdG. Study participants with lower alpha-tocopherol and higher urinary total arsenic, higher InAs%, higher MMA%, and lower DMA% had a higher UC risk than those with higher alpha-tocopherol and lower urinary total arsenic, lower InAs%, lower MMA%, and higher DMA%. These results suggest that plasma alpha-tocopherol might modify the risk of inorganic arsenic-related UC. - Research Highlights: → Plasma alpha-tocopherol levels were significantly inversely related to UC risk. → There were no correlations between plasma micronutrients and urinary 8-OHdG. → People with lower alpha-tocopherol and higher total arsenic had increased UC risk.

  19. Protective effects of plasma alpha-tocopherols on the risk of inorganic arsenic-related urothelial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Chi-Jung [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China); Chen, Ying-Ting [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Su, Chien-Tien [Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Wu, Chia-Chang [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Urology, Taipei Medical Universtiy-Shuang Ho Hospital, Taipei, Taiwan (China); Shiue, Horng-Sheng [Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan (China); Huang, Chao-Yuan [Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China); Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2011-02-15

    Arsenic plays an important role in producing oxidative stress in cultured cells. To investigate the interaction between high oxidative stress and low arsenic methylation capacity on arsenic carcinogenesis, a case-control study was conducted to evaluate the relationship among the indices of oxidative stress, such as urinary 8-hydroxydeoxyquanine (8-OHdG), as well as plasma micronutrients and urinary arsenic profiles on urothelial carcinoma (UC) risk. Urinary 8-OHdG was measured using high-sensitivity enzyme-linked immunosorbent assay kits. The urinary arsenic species were analyzed using high-performance liquid chromatography and hydride generator-atomic absorption spectrometry. Plasma micronutrient levels were analyzed using reversed-phase high-performance liquid chromatography. The present study showed a significant protective effect of plasma alpha-tocopherol on UC risk. Plasma alpha-tocopherol levels were significantly inversely related to urinary total arsenic concentrations and inorganic arsenic percentage (InAs%), and significantly positively related to dimethylarsinic acid percentage (DMA%). There were no correlations between plasma micronutrients and urinary 8-OHdG. Study participants with lower alpha-tocopherol and higher urinary total arsenic, higher InAs%, higher MMA%, and lower DMA% had a higher UC risk than those with higher alpha-tocopherol and lower urinary total arsenic, lower InAs%, lower MMA%, and higher DMA%. These results suggest that plasma alpha-tocopherol might modify the risk of inorganic arsenic-related UC. - Research Highlights: {yields} Plasma alpha-tocopherol levels were significantly inversely related to UC risk. {yields} There were no correlations between plasma micronutrients and urinary 8-OHdG. {yields} People with lower alpha-tocopherol and higher total arsenic had increased UC risk.

  20. COMPARATIVE TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC (IAS) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (ASV) AND ARSENITE (ASIII)

    Science.gov (United States)

    COMPARATIVE TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC (iAs) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (AsV) AND ARSENITE (AsIII). E M Kenyon, L M Del Razo and M F Hughes. U.S. EPA, ORD, NHEERL, ETD, PKB, RTP, NC, USA; ...

  1. Duodenal L cell density correlates with features of metabolic syndrome and plasma metabolites

    Directory of Open Access Journals (Sweden)

    Annieke C G van Baar

    2018-05-01

    Full Text Available Background: Enteroendocrine cells are essential for the regulation of glucose metabolism, but it is unknown whether they are associated with clinical features of metabolic syndrome (MetS and fasting plasma metabolites. Objective: We aimed to identify fasting plasma metabolites that associate with duodenal L cell, K cell and delta cell densities in subjects with MetS with ranging levels of insulin resistance. Research design and methods: In this cross-sectional study, we evaluated L, K and delta cell density in duodenal biopsies from treatment-naïve males with MetS using machine-learning methodology. Results: We identified specific clinical biomarkers and plasma metabolites associated with L cell and delta cell density. L cell density was associated with increased plasma metabolite levels including symmetrical dimethylarginine, 3-aminoisobutyric acid, kynurenine and glycine. In turn, these L cell-linked fasting plasma metabolites correlated with clinical features of MetS. Conclusions: Our results indicate a link between duodenal L cells, plasma metabolites and clinical characteristics of MetS. We conclude that duodenal L cells associate with plasma metabolites that have been implicated in human glucose metabolism homeostasis. Disentangling the causal relation between L cells and these metabolites might help to improve the (small intestinal-driven pathophysiology behind insulin resistance in human obesity.

  2. Direct analysis and stability of methylated trivalent arsenic metabolites in cells and tissues

    Czech Academy of Sciences Publication Activity Database

    Currier, J. M.; Svoboda, Milan; Matoušek, Tomáš; Dědina, Jiří; Stýblo, M.

    2011-01-01

    Roč. 3, č. 12 (2011), s. 1347-1354 ISSN 1756-5901 R&D Projects: GA ČR GA203/09/1783 Institutional research plan: CEZ:AV0Z40310501 Keywords : arsenic speciation * tissue * hydride generation Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 3.902, year: 2011

  3. Differences of Urinary Arsenic Metabolites and Methylation Capacity between Individuals with and without Skin Lesions in Inner Mongolia, Northern China

    Directory of Open Access Journals (Sweden)

    Qiang Zhang

    2014-07-01

    Full Text Available Incomplete arsenic (As methylation has been considered a risk factor of As-related diseases. This study aimed to examine the difference of urinary As metabolites and the methylation capacity between subjects with and without skin lesions. Urinary inorganic arsenic (iAs, monomethylarsonic acid (MMA, and dimethylarsinic acid (DMA were analyzed. The percentage of each As species (iAs%, MMA%, and DMA%, the primary methylation index (PMI and secondary methylation index (SMI were calculated. The results showed that subjects with skin lesions have higher levels of urinary iAs (99.08 vs. 70.63 μg/g Cr, p = 0.006 and MMA (69.34 vs. 42.85 μg/g Cr, p = 0.016 than subjects without skin lesions after adjustment for several confounders. Significant differences of urianry MMA% (15.49 vs. 12.11, p = 0.036 and SMI (0.74 vs. 0.81, p = 0.025 were found between the two groups. The findings of the present study suggest that subjects with skin lesions may have a lower As methylation capacity than subjects without skin lesions.

  4. Differences of urinary arsenic metabolites and methylation capacity between individuals with and without skin lesions in Inner Mongolia, Northern China.

    Science.gov (United States)

    Zhang, Qiang; Li, Yongfang; Liu, Juan; Wang, Da; Zheng, Quanmei; Sun, Guifan

    2014-07-18

    Incomplete arsenic (As) methylation has been considered a risk factor of As-related diseases. This study aimed to examine the difference of urinary As metabolites and the methylation capacity between subjects with and without skin lesions. Urinary inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were analyzed. The percentage of each As species (iAs%, MMA%, and DMA%), the primary methylation index (PMI) and secondary methylation index (SMI) were calculated. The results showed that subjects with skin lesions have higher levels of urinary iAs (99.08 vs. 70.63 μg/g Cr, p = 0.006) and MMA (69.34 vs. 42.85 μg/g Cr, p = 0.016) than subjects without skin lesions after adjustment for several confounders. Significant differences of urianry MMA% (15.49 vs. 12.11, p = 0.036) and SMI (0.74 vs. 0.81, p = 0.025) were found between the two groups. The findings of the present study suggest that subjects with skin lesions may have a lower As methylation capacity than subjects without skin lesions.

  5. Arsenic in Food

    Science.gov (United States)

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Food Home Food Foodborne Illness & Contaminants Metals Arsenic Share ... of the Method used to Measure Arsenic in Foods Inductively Coupled Plasma-Mass Spectrometric Determination of Arsenic, ...

  6. Elevated levels of plasma uric acid and its relation to hypertension in arsenic-endemic human individuals in Bangladesh

    International Nuclear Information System (INIS)

    Huda, Nazmul; Hossain, Shakhawoat; Rahman, Mashiur; Karim, Md. Rezaul; Islam, Khairul; Mamun, Abdullah Al; Hossain, Md. Imam; Mohanto, Nayan Chandra; Alam, Shahnur; Aktar, Sharmin; Arefin, Afroza; Ali, Nurshad; Salam, Kazi Abdus; Aziz, Abdul; Saud, Zahangir Alam; Miyataka, Hideki; Himeno, Seiichiro; Hossain, Khaled

    2014-01-01

    Blood uric acid has been recognized as a putative marker for cardiovascular diseases (CVDs). CVDs are the major causes of arsenic-related morbidity and mortality. However, the association of arsenic exposure with plasma uric acid (PUA) levels in relation to CVDs has not yet been explored. This study for the first time demonstrated the associations of arsenic exposure with PUA levels and its relationship with hypertension. A total of 483 subjects, 322 from arsenic-endemic and 161 from non-endemic areas in Bangladesh were recruited as study subjects. Arsenic concentrations in the drinking water, hair and nails of the study subjects were measured by inductively coupled plasma mass spectroscopy. PUA levels were measured using a colorimetric method. We found that PUA levels were significantly (p < 0.001) higher in males and females living in arsenic-endemic areas than those in non-endemic area. Arsenic exposure (water, hair and nail arsenic) levels showed significant positive correlations with PUA levels. In multiple regression analyses, arsenic exposure levels were found to be the most significant contributors on PUA levels among the other variables that included age, body mass index, blood urea nitrogen, and smoking. There were dose–response relationships between arsenic exposure and PUA levels. Furthermore, diastolic and systolic blood pressure showed significant positive correlations with PUA levels. Finally, the average PUA levels were significantly higher in the hypertensive group than those in the normotensive group in both males and females living in arsenic-endemic areas. These results suggest that arsenic exposure-related elevation of PUA levels may be implicated in arsenic-induced CVDs. - Highlights: • PUA levels were higher in arsenic-endemic subjects than in non-endemic subjects. • Drinking water, hair and nail arsenic showed significant associations with PUA levels. • Drinking water, hair and nail arsenic showed dose–response relationships with

  7. Elevated levels of plasma uric acid and its relation to hypertension in arsenic-endemic human individuals in Bangladesh

    Energy Technology Data Exchange (ETDEWEB)

    Huda, Nazmul [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi 6205 (Bangladesh); Department of Medicine, Rajshahi Medical College, Rajshahi 6000 (Bangladesh); Hossain, Shakhawoat; Rahman, Mashiur [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi 6205 (Bangladesh); Karim, Md. Rezaul [Department of Applied Nutrition and Food Technology, Islamic University, Kushtia 7003 (Bangladesh); Islam, Khairul [Department of Biochemistry and Molecular Biology, Mawlana Bhashani Science and Technology University, Santosh, Tangail 1902 (Bangladesh); Mamun, Abdullah Al; Hossain, Md. Imam; Mohanto, Nayan Chandra; Alam, Shahnur; Aktar, Sharmin; Arefin, Afroza; Ali, Nurshad; Salam, Kazi Abdus; Aziz, Abdul; Saud, Zahangir Alam [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi 6205 (Bangladesh); Miyataka, Hideki; Himeno, Seiichiro [Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8514 (Japan); Hossain, Khaled, E-mail: khossainbio@gmail.com [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi 6205 (Bangladesh)

    2014-11-15

    Blood uric acid has been recognized as a putative marker for cardiovascular diseases (CVDs). CVDs are the major causes of arsenic-related morbidity and mortality. However, the association of arsenic exposure with plasma uric acid (PUA) levels in relation to CVDs has not yet been explored. This study for the first time demonstrated the associations of arsenic exposure with PUA levels and its relationship with hypertension. A total of 483 subjects, 322 from arsenic-endemic and 161 from non-endemic areas in Bangladesh were recruited as study subjects. Arsenic concentrations in the drinking water, hair and nails of the study subjects were measured by inductively coupled plasma mass spectroscopy. PUA levels were measured using a colorimetric method. We found that PUA levels were significantly (p < 0.001) higher in males and females living in arsenic-endemic areas than those in non-endemic area. Arsenic exposure (water, hair and nail arsenic) levels showed significant positive correlations with PUA levels. In multiple regression analyses, arsenic exposure levels were found to be the most significant contributors on PUA levels among the other variables that included age, body mass index, blood urea nitrogen, and smoking. There were dose–response relationships between arsenic exposure and PUA levels. Furthermore, diastolic and systolic blood pressure showed significant positive correlations with PUA levels. Finally, the average PUA levels were significantly higher in the hypertensive group than those in the normotensive group in both males and females living in arsenic-endemic areas. These results suggest that arsenic exposure-related elevation of PUA levels may be implicated in arsenic-induced CVDs. - Highlights: • PUA levels were higher in arsenic-endemic subjects than in non-endemic subjects. • Drinking water, hair and nail arsenic showed significant associations with PUA levels. • Drinking water, hair and nail arsenic showed dose–response relationships with

  8. Haloperidol response and plasma catecholamines and their metabolites.

    Science.gov (United States)

    Green, A I; Alam, M Y; Boshes, R A; Waternaux, C; Pappalardo, K M; Fitzgibbon, M E; Tsuang, M T; Schildkraut, J J

    1993-06-01

    Eleven acutely psychotic patients with schizophrenia or schizoaffective disorder underwent a 5-7 day drug-washout period (with lorazepam allowed) prior to participating in a 6-week controlled dose haloperidol trial. Patients were evaluated longitudinally with clinical ratings and with plasma measures of the catecholamines dopamine (pDA) and norepinephrine (pNE) and their metabolites, homovanillic acid (pHVA) and 3-methoxy-4-hydroxyphenylglycol (pMHPG). All patients exhibited clinical improvement with haloperidol; the decrease in their Brief Psychiatric Rating Scale (BPRS) scores ranged from 32 to 89%. Measures of pHVA increased within the first week of treatment and returned to baseline by week 5. The pattern of change of pDA resembled that of pHVA. The pattern of change of pNE and pMHPG revealed a decrease over the course of treatment. The early increase and the subsequent decrease in pHVA were strongly correlated with improvement in positive symptoms on the BPRS. These data are consistent with previous reports on the change in pHVA and pMHPG during clinical response to haloperidol. The data on change of pDA and pNE further describe the nature of the biochemical response to this drug.

  9. Determination of epirubicin and its metabolite epirubicinol in saliva and plasma by HPLC

    NARCIS (Netherlands)

    Dodde, WIW; Maring, JG; Hendriks, G; Wachters, FM; Groen, HJM; de Vries, EGE; Uges, DRA

    We present a high-performance liquid chromatography (HPLC) method suitable for the analysis of epirubicin and its metabolite epirubicinol in saliva and plasma. Preparation of saliva and plasma samples was performed by extraction of analytes with a chloroform: 2-propanol mixture (6:1, vol/vol) and

  10. Effect of plasma homocysteine level and urinary monomethylarsonic acid on the risk of arsenic-associated carotid atherosclerosis

    International Nuclear Information System (INIS)

    Wu, M.-M.; Chiou, H.-Y.; Hsueh, Y.-M.; Hong, C.-T.; Su, C.-L.; Chang, S.-F.; Huang, W.-L.; Wang, H.-T.; Wang, Y.-H.; Hsieh, Y.-C.; Chen, C.-J.

    2006-01-01

    Arsenic-contaminated well water has been shown to increase the risk of atherosclerosis. Because of involving S-adenosylmethionine, homocysteine may modify the risk by interfering with the biomethylation of ingested arsenic. In this study, we assessed the effect of plasma homocysteine level and urinary monomethylarsonic acid (MMA V ) on the risk of atherosclerosis associated with arsenic. In total, 163 patients with carotid atherosclerosis and 163 controls were studied. Lifetime cumulative arsenic exposure from well water for study subjects was measured as index of arsenic exposure. Homocysteine level was determined by high-performance liquid chromatography (HPLC). Proportion of MMA V (MMA%) was calculated by dividing with total arsenic species in urine, including arsenite, arsenate, MMA V , and dimethylarsinic acid (DMA V ). Results of multiple linear regression analysis show a positive correlation of plasma homocysteine levels to the cumulative arsenic exposure after controlling for atherosclerosis status and nutritional factors (P < 0.05). This correlation, however, did not change substantially the effect of arsenic exposure on the risk of atherosclerosis as analyzed in a subsequent logistic regression model. Logistic regression analyses also show that elevated plasma homocysteine levels did not confer an independent risk for developing atherosclerosis in the study population. However, the risk of having atherosclerosis was increased to 5.4-fold (95% CI, 2.0-15.0) for the study subjects with high MMA% (≥16.5%) and high homocysteine levels (≥12.7 μmol/l) as compared to those with low MMA% (<9.9%) and low homocysteine levels (<12.7 μmol/l). Elevated homocysteinemia may exacerbate the formation of atherosclerosis related to arsenic exposure in individuals with high levels of MMA% in urine

  11. Supplementation with Folic Acid, but Not Creatine, Increases Plasma Betaine, Decreases Plasma Dimethylglycine, and Prevents a Decrease in Plasma Choline in Arsenic-Exposed Bangladeshi Adults.

    Science.gov (United States)

    Hall, Megan N; Howe, Caitlin G; Liu, Xinhua; Caudill, Marie A; Malysheva, Olga; Ilievski, Vesna; Lomax-Luu, Angela M; Parvez, Faruque; Siddique, Abu B; Shahriar, Hasan; Uddin, Mohammad N; Islam, Tariqul; Graziano, Joseph H; Gamble, Mary V

    2016-05-01

    Folic acid (FA) supplementation facilitates urinary excretion of arsenic, a human carcinogen. A better understanding of interactions between one-carbon metabolism intermediates may improve the ability to design nutrition interventions that further facilitate arsenic excretion. The objective was to determine if FA and/or creatine supplementation increase choline and betaine and decrease dimethylglycine (DMG). We conducted a secondary analysis of the Folic Acid and Creatine Trial, a randomized trial in arsenic-exposed Bangladeshi adults (n = 605, aged 24-55 y, 50.3% male) who received arsenic-removal water filters. We examined treatment effects of FA and/or creatine supplementation on plasma choline, betaine, and DMG concentrations, measured by LC-tandem mass spectrometry at baseline and at week 12. Group comparisons were between 1) 400 and 800 μg FA/d (FA400 and FA800, respectively) compared with placebo, 2) creatine (3 g/d) compared with placebo, and 3) creatine plus FA400 compared with FA400. Choline decreased in the placebo group (-6.6%; 95% CI: -10.2%, -2.9%) but did not change in the FA groups (FA400: 2.5%; 95% CI: -0.9%, 6.1%; FA800: 1.4%; 95% CI: -2.5%, 5.5%; P creatine treatment arms and their respective reference groups. Supplementation for 12 wk with FA, but not creatine, increases plasma betaine, decreases plasma DMG, and prevents a decrease in plasma choline in arsenic-exposed Bangladeshi adults. This trial was registered at clinicaltrials.gov as NCT01050556. © 2016 American Society for Nutrition.

  12. Promising Metabolite Profiles in the Plasma and CSF of Early Clinical Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Daniel Stoessel

    2018-03-01

    Full Text Available Parkinson's disease (PD shows high heterogeneity with regard to the underlying molecular pathogenesis involving multiple pathways and mechanisms. Diagnosis is still challenging and rests entirely on clinical features. Thus, there is an urgent need for robust diagnostic biofluid markers. Untargeted metabolomics allows establishing low-molecular compound biomarkers in a wide range of complex diseases by the measurement of various molecular classes in biofluids such as blood plasma, serum, and cerebrospinal fluid (CSF. Here, we applied untargeted high-resolution mass spectrometry to determine plasma and CSF metabolite profiles. We semiquantitatively determined small-molecule levels (≤1.5 kDa in the plasma and CSF from early PD patients (disease duration 0–4 years; n = 80 and 40, respectively, and sex- and age-matched controls (n = 76 and 38, respectively. We performed statistical analyses utilizing partial least square and random forest analysis with a 70/30 training and testing split approach, leading to the identification of 20 promising plasma and 14 CSF metabolites. These metabolites differentiated the test set with an AUC of 0.8 (plasma and 0.9 (CSF. Characteristics of the metabolites indicate perturbations in the glycerophospholipid, sphingolipid, and amino acid metabolism in PD, which underscores the high power of metabolomic approaches. Further studies will enable to develop a potential metabolite-based biomarker panel specific for PD.

  13. Microdose clinical trial: quantitative determination of nicardipine and prediction of metabolites in human plasma.

    Science.gov (United States)

    Yamane, Naoe; Takami, Tomonori; Tozuka, Zenzaburo; Sugiyama, Yuichi; Yamazaki, Akira; Kumagai, Yuji

    2009-01-01

    A sample treatment procedure and high-sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for quantitative determination of nicardipine in human plasma were developed for a microdose clinical trial with nicardipine, a non-radioisotope labeled drug. The calibration curve was linear in the range of 1-500 pg/mL using 1 mL of plasma. Analytical method validation for the clinical dose, for which the calibration curve was linear in the range of 0.2-100 ng/mL using 20 microL of plasma, was also conducted. Each method was successfully applied to making determinations in plasma using LC/MS/MS after administration of a microdose (100 microg) and clinical dose (20 mg) to each of six healthy volunteers. We tested new approaches in the search for metabolites in plasma after microdosing. In vitro metabolites of nicardipine were characterized using linear ion trap-fourier transform ion cyclotron resonance mass spectrometry (LIT-FTICRMS) and the nine metabolites predicted to be in plasma were analyzed using LC/MS/MS. There is a strong possibility that analysis of metabolites by LC/MS/MS may advance to utilization in microdose clinical trials with non-radioisotope labeled drugs.

  14. Association between plasma metabolites and gene expression profiles in five porcine endocrine tissues

    Directory of Open Access Journals (Sweden)

    Bassols Anna

    2011-07-01

    Full Text Available Abstract Background Endocrine tissues play a fundamental role in maintaining homeostasis of plasma metabolites such as non-esterified fatty acids and glucose, the levels of which reflect the energy balance or the health status of animals. However, the relationship between the transcriptome of endocrine tissues and plasma metabolites has been poorly studied. Methods We determined the blood levels of 12 plasma metabolites in 27 pigs belonging to five breeds, each breed consisting of both females and males. The transcriptome of five endocrine tissues i.e. hypothalamus, adenohypophysis, thyroid gland, gonads and backfat tissues from 16 out of the 27 pigs was also determined. Sex and breed effects on the 12 plasma metabolites were investigated and associations between genes expressed in the five endocrine tissues and the 12 plasma metabolites measured were analyzed. A probeset was defined as a quantitative trait transcript (QTT when its association with a particular metabolic trait achieved a nominal P value Results A larger than expected number of QTT was found for non-esterified fatty acids and alanine aminotransferase in at least two tissues. The associations were highly tissue-specific. The QTT within the tissues were divided into co-expression network modules enriched for genes in Kyoto Encyclopedia of Genes and Genomes or gene ontology categories that are related to the physiological functions of the corresponding tissues. We also explored a multi-tissue co-expression network using QTT for non-esterified fatty acids from the five tissues and found that a module, enriched in hypothalamus QTT, was positioned at the centre of the entire multi-tissue network. Conclusions These results emphasize the relationships between endocrine tissues and plasma metabolites in terms of gene expression. Highly tissue-specific association patterns suggest that candidate genes or gene pathways should be investigated in the context of specific tissues.

  15. Arsenic speciation in soil using high performance liquid chromatography/inductively coupled plasma/mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Bass, D.A.; Yaeger, J.S.; Parish, K.J.; Crain, J.S.; Kiely, J.T.; Gowdy, M.J. [Argonne National Lab., IL (United States); Mohrman, G.B.; Besmer, M.G. [Rocky Mountain Arsenal, Commerce City, CO (United States)

    1996-08-01

    A method has been developed to identify and quantify As(III), As(V), and organoarsenic compounds in soil samples from the Rocky Mountain Arsenal (RMA) by high performance liquid chromatography/inductively coupled plasma/mass spectrometry (HPLC/ICP/MS). The soils were extracted using tetrabutylammonium hydroxide (TBAH) and sonication. The percentages of As(III), As(V), and organoarsenic species extracted from soil samples were 30, 50, and 100 respectively. The arsenic species were not altered during the extraction process. They were separated by reversed-phase, ion-pairing, HPLC using a microbore Inertsil-ODS{trademark} column. The HPLC column effluent was introduced into an ICP/MS system using a direct injection nebulizer (DIN). Detection limits of less than 1 pg were readily obtained for each arsenic species. Internal standards are recommended to increase accuracy and precision. Soil samples spiked with arsenic oxide, sodium arsenate, dimethylarsinic acid (DMAA), and chlorovinyl arsenious acid (CVAA) were extracted, identified and quantified with the HPLC/ICP/MS system. The soil samples were analyzed in support of the analytical needs of a thermal desorption treatability study being conducted at the RMA.

  16. High-performance liquid chromatographic separation of biologically important arsenic species utilizing on-line inductively coupled argon plasma atomic emission spectrometric detection

    Energy Technology Data Exchange (ETDEWEB)

    Spall, W.D.; Lynn, J.G.; Andersen, J.L.; Valdez, J.G.; Gurley, L.R.

    1986-06-01

    An anion exchange, high-performance liquid chromatography technique using a 15-min linear gradient from water to 0.5 M ammonium carbonate to separate arsenite, arsenate, methylarsonic acid, and dimethylarsinic acid from neutral arsenic containing compounds was developed for application to a study of arsenic metabolism in cultured cell suspensions. Arsenic detection was accomplished by the direct coupling of the column effluent to an inductively coupled argon plasma atomic emission spectrometer (ICAP-AES) set to monitor the arsenic emission line at 197.19 nm. The analysis requires 20 min and is sensitive to as low as 60 ng of arsenic injected to the column.

  17. Pyometra in Bitches Induces Elevated Plasma Endotoxin and Prostaglandin F2α Metabolite Levels

    Directory of Open Access Journals (Sweden)

    Hagman R

    2006-03-01

    Full Text Available Endotoxemia in bitches with pyometra can cause severe systemic effects directly or via the release of inflammatory mediators. Plasma endotoxin concentrations were measured in ten bitches suffering from pyometra with moderately to severely deteriorated general condition, and in nine bitches admitted to surgery for non-infectious reasons. Endotoxin samples were taken on five occasions before, during and after surgery. In addition, urine and uterine bacteriology was performed and hematological, blood biochemical parameters, prostaglandin F2α metabolite 15-ketodihydro-PGF2α (PG-metabolite, progesterone and oestradiol (E2-17β levels were analysed. The results confirm significantly increased plasma levels of endotoxin in bitches with pyometra and support previous reports of endotoxin involvement in the pathogenesis of the disease. Plasma concentrations of PG-metabolite were elevated in pyometra bitches and provide a good indicator of endotoxin release since the concentrations were significantly correlated to the endotoxin levels and many other hematological and chemistry parameters. The γ-globulin serum protein electrophoresis fraction and analysis of PG-metabolite can be valuable in the diagnosis of endotoxin involvement if a reliable, rapid and cost-effective test for PG-metabolite analysis becomes readily available in the future. Treatment inhibiting prostaglandin biosynthesis and related compounds could be beneficial for bitches suffering from pyometra.

  18. Inductively coupled plasma mass spectrometry study of the retention behavior of arsenic species on various solid phase extraction cartridges and its application in arsenic speciation

    Energy Technology Data Exchange (ETDEWEB)

    Yu Chunhai; Cai Qiantao E-mail: qtcai@cawt.sui.com.sg; Guo Zhongxian; Yang Zhaoguang; Khoo, Soo Beng

    2003-07-18

    Inductively coupled plasma mass spectrometry (ICP-MS) was used to investigate the retention behavior of arsenite, arsenate, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), arsenobetaine (AsB), arsenocholine (AsC), trimethylarsine oxide (TMAO) and tetramethylarsonium ion (TMAI) on various silica-based solid phase extraction (SPE) cartridges. A method for arsenic speciation is then developed on the basis of selective SPE separation of arsenic species and highly sensitive ICP-MS detection. Factors affecting the retention and elution of arsenic species were examined. Results showed that the retention of arsenic species depended on the chemical characteristics of arsenic species and the types of sorbent materials. Change of pH in the range of 2.0-9.0 did not show significant effects on the retention of DMA, AsB, AsC, TMAI and TMAO on an ethylbenzene sulfonic acid-based strong cation exchange (SCX-3) cartridge. pH also did not influence the retention of AsB, AsC, TMAI and TMAO on a mixed-mode (M-M) cartridge containing non-polar, strong cation exchange and strong anion exchange (SAX) functional groups. However, the retentions of As(V) and MMA on the SAX and the M-M cartridge changed with pH. As(V) and MMA were completely retained on the SAX cartridge and sequentially selectively eluted with 1.0 mol l{sup -1} acetic acid (for MMA). DMA, AsB, AsC, TMAI and TMAO were completely retained on the SCX-3 cartridge and sequentially selectively eluted with 1.0 mol l{sup -1} HNO{sub 3} (for DMA). As(V), MMA, AsB, AsC, TMAI and TMAO were completely retained on the M-M cartridge. As(III) was not retained on either cartridge and remained in solution. Arsenic species in solution and those eluted from the cartridges were subsequently determined by ICP-MS. A detection limit of 8 ng l{sup -1} arsenic in water sample was obtained. This method was successfully applied to arsenic speciation in various sources of water samples (drinking water, waste water, raw water, etc.) and US

  19. Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa.

    Science.gov (United States)

    Näsström, Elin; Parry, Christopher M; Vu Thieu, Nga Tran; Maude, Rapeephan R; de Jong, Hanna K; Fukushima, Masako; Rzhepishevska, Olena; Marks, Florian; Panzner, Ursula; Im, Justin; Jeon, Hyonjin; Park, Seeun; Chaudhury, Zabeen; Ghose, Aniruddha; Samad, Rasheda; Van, Tan Trinh; Johansson, Anders; Dondorp, Arjen M; Thwaites, Guy E; Faiz, Abul; Antti, Henrik; Baker, Stephen

    2017-05-09

    Salmonella Typhi is the causative agent of typhoid. Typhoid is diagnosed by blood culture, a method that lacks sensitivity, portability and speed. We have previously shown that specific metabolomic profiles can be detected in the blood of typhoid patients from Nepal (Näsström et al., 2014). Here, we performed mass spectrometry on plasma from Bangladeshi and Senegalese patients with culture confirmed typhoid fever, clinically suspected typhoid, and other febrile diseases including malaria. After applying supervised pattern recognition modelling, we could significantly distinguish metabolite profiles in plasma from the culture confirmed typhoid patients. After comparing the direction of change and degree of multivariate significance, we identified 24 metabolites that were consistently up- or down regulated in a further Bangladeshi/Senegalese validation cohort, and the Nepali cohort from our previous work. We have identified and validated a metabolite panel that can distinguish typhoid from other febrile diseases, providing a new approach for typhoid diagnostics.

  20. Plasma and Serum Metabolite Association Networks: Comparability within and between Studies Using NMR and MS Profiling.

    Science.gov (United States)

    Suarez-Diez, Maria; Adam, Jonathan; Adamski, Jerzy; Chasapi, Styliani A; Luchinat, Claudio; Peters, Annette; Prehn, Cornelia; Santucci, Claudio; Spyridonidis, Alexandros; Spyroulias, Georgios A; Tenori, Leonardo; Wang-Sattler, Rui; Saccenti, Edoardo

    2017-07-07

    Blood is one of the most used biofluids in metabolomics studies, and the serum and plasma fractions are routinely used as a proxy for blood itself. Here we investigated the association networks of an array of 29 metabolites identified and quantified via NMR in the plasma and serum samples of two cohorts of ∼1000 healthy blood donors each. A second study of 377 individuals was used to extract plasma and serum samples from the same individual on which a set of 122 metabolites were detected and quantified using FIA-MS/MS. Four different inference algorithms (ARANCE, CLR, CORR, and PCLRC) were used to obtain consensus networks. The plasma and serum networks obtained from different studies showed different topological properties with the serum network being more connected than the plasma network. On a global level, metabolite association networks from plasma and serum fractions obtained from the same blood sample of healthy people show similar topologies, and at a local level, some differences arise like in the case of amino acids.

  1. Effect of metformin on plasma metabolite profile in the Copenhagen Insulin and Metformin Therapy (CIMT) trial

    DEFF Research Database (Denmark)

    Safai, N; Suvitaival, T; A, Ali

    2018-01-01

    of the Copenhagen Insulin and Metformin Therapy (CMIT) trial, a multicentre study from May 2008 to December 2012, was carried out. We used a non-target method to analyse 87 plasma metabolites in participants with Type 2 diabetes (n = 370) who were randomized in a 1 : 1 ratio to 18 months of metformin or placebo...

  2. Impact of nutrient excess and endothelial nitric oxide synthase on the plasma metabolite profile in mice

    Directory of Open Access Journals (Sweden)

    Brian E Sansbury

    2014-11-01

    Full Text Available An increase in calorie consumption is associated with the recent rise in obesity prevalence. However, our current understanding of the effects of nutrient excess on major metabolic pathways appears insufficient to develop safe and effective metabolic interventions to prevent obesity. Hence, we sought to identify systemic metabolic changes caused by nutrient excess and to determine how endothelial nitric oxide synthase (eNOS—which has anti-obesogenic properties—affects systemic metabolism by measuring plasma metabolites. Wild-type (WT and eNOS transgenic (eNOS-TG mice were placed on low fat or high fat diets for six weeks, and plasma metabolites were measured using an unbiased metabolomic approach. High fat feeding in WT mice led to significant increases in fat mass, which was associated with significantly lower plasma levels of 1,5-anhydroglucitol, lysophospholipids, 3-dehydrocarnitine, and bile acids, as well as branched chain amino acids (BCAAs and their metabolites. Plasma levels of several lipids including sphingomyelins, stearoylcarnitine, dihomo-linoleate and metabolites associated with oxidative stress were increased by high fat diet. In comparison with low fat-fed WT mice, eNOS-TG mice showed lower levels of several free fatty acids, but in contrast, the levels of bile acids, amino acids, and BCAA catabolites were increased. When placed on a high fat diet, eNOS overexpressing mice showed remarkably higher levels of plasma bile acids and elevated levels of plasma BCAAs and their catabolites compared with WT mice. Treatment with GW4064, an inhibitor of bile acid synthesis, decreased plasma bile acid levels but was not sufficient to reverse the anti-obesogenic effects of eNOS overexpression. These findings reveal unique metabolic changes in response to high fat diet and eNOS overexpression and suggest that the anti-obesity effects of eNOS are likely independent of changes in the bile acid pool.

  3. Supplementation with Folic Acid, but Not Creatine, Increases Plasma Betaine, Decreases Plasma Dimethylglycine, and Prevents a Decrease in Plasma Choline in Arsenic-Exposed Bangladeshi Adults123

    Science.gov (United States)

    Hall, Megan N; Liu, Xinhua; Caudill, Marie A; Malysheva, Olga; Ilievski, Vesna; Lomax-Luu, Angela M; Parvez, Faruque; Siddique, Abu B; Shahriar, Hasan; Uddin, Mohammad N; Islam, Tariqul; Graziano, Joseph H; Gamble, Mary V

    2016-01-01

    Background: Folic acid (FA) supplementation facilitates urinary excretion of arsenic, a human carcinogen. A better understanding of interactions between one-carbon metabolism intermediates may improve the ability to design nutrition interventions that further facilitate arsenic excretion. Objective: The objective was to determine if FA and/or creatine supplementation increase choline and betaine and decrease dimethylglycine (DMG). Methods: We conducted a secondary analysis of the Folic Acid and Creatine Trial, a randomized trial in arsenic-exposed Bangladeshi adults (n = 605, aged 24–55 y, 50.3% male) who received arsenic-removal water filters. We examined treatment effects of FA and/or creatine supplementation on plasma choline, betaine, and DMG concentrations, measured by LC–tandem mass spectrometry at baseline and at week 12. Group comparisons were between 1) 400 and 800 μg FA/d (FA400 and FA800, respectively) compared with placebo, 2) creatine (3 g/d) compared with placebo, and 3) creatine plus FA400 compared with FA400. Results: Choline decreased in the placebo group (−6.6%; 95% CI: −10.2%, −2.9%) but did not change in the FA groups (FA400: 2.5%; 95% CI: −0.9%, 6.1%; FA800: 1.4%; 95% CI: −2.5%, 5.5%; P DMG was greater in the FA groups (FA400: −26.7%; 95% CI: −30.9%, −22.2%; FA800: −27.8%; 95% CI: −31.8%, −23.4%) than in the placebo group (−12.3%; 95% CI: −18.1%, −6.2%; P DMG did not differ between creatine treatment arms and their respective reference groups. Conclusion: Supplementation for 12 wk with FA, but not creatine, increases plasma betaine, decreases plasma DMG, and prevents a decrease in plasma choline in arsenic-exposed Bangladeshi adults. This trial was registered at clinicaltrials.gov as NCT01050556. PMID:27052531

  4. Speciation of arsenic in human nail and hair from arsenic-affected area by HPLC-inductively coupled argon plasma mass spectrometry

    International Nuclear Information System (INIS)

    Mandal, Badal Kumar; Ogra, Yasumitsu; Suzuki, Kazuo T.

    2003-01-01

    Nail and hair are rich in fibrous proteins, i.e., α-keratins that contain abundant cysteine residues (up to 22% in nail and 10-14% in hair). Although they are metabolically dead materials in the epidermis, the roots are highly influenced by the health status of the living beings and their analyses are used as a tool to monitor occupational and environmental exposure to toxic elements. The aims of the present study are to speciate arsenicals in human nail and hair and also to judge whether they should be used as a biomarker to arsenic (As) exposure and/or toxicity. All human fingernail and hair samples (n = 47) were collected from the As-affected area of West Bengal, India. Speciation of arsenicals in water extracts of fingernails and hair at 90 degree sign C was carried out by HPLC-inductively coupled argon plasma mass spectrometer (ICP MS). Fingernails contained iAs III (58.6%), iAs V (21.5), MMA V (7.7), DMA III (9.2), and DMA V (3.0), and hair contained iAs III (60.9%), iAs V (33.2), MMA V (2.2), and DMA V (3.6). Fingernails contained DMA III , but hair did not. The higher percentage of iAs III both in fingernails and hair than that of iAs V suggests more affinity of iAs III to keratin. Although all arsenicals in fingernails and hair correlate to As exposure positively, As speciation in fingernails seems to be more correlated with arsenism than that in hair. Exogenous contamination is a confounding factor for hair to consider it as a biomarker, whereas this is mostly absent in fingernails, which recommends it to be a better biomarker to arsenic exposure. DMA III content in fingernails and DMA V contents in both fingernails and hair could be the biomarker to As exposure

  5. GMP-compliant radiosynthesis of [{sup 18}F]altanserin and human plasma metabolite studies

    Energy Technology Data Exchange (ETDEWEB)

    Hasler, F. [University Hospital of Psychiatry, Heffter Research Center, Zurich (Switzerland)], E-mail: fehasler@bli.uzh.ch; Kuznetsova, O.F.; Krasikova, R.N. [Institute of the Human Brain, Russian Academy of Science, St. Petersburg (Russian Federation); Cservenyak, T. [Center for Radiopharmaceutical Sciences of ETH, PSI and University Hospital Zurich (Switzerland); Quednow, B.B.; Vollenweider, F.X. [University Hospital of Psychiatry, Heffter Research Center, Zurich (Switzerland); Ametamey, S.M.; Westera, G. [Center for Radiopharmaceutical Sciences of ETH, PSI and University Hospital Zurich (Switzerland)

    2009-04-15

    [{sup 18}F]altanserin is the preferred radiotracer for in-vivo labeling of serotonin 2A receptors by positron emission tomography (PET). We report a modified synthesis procedure suited for reliable production of multi-GBq amounts of [{sup 18}F]altanserin useful for application in humans. We introduced thermal heating for drying of [{sup 18}F]fluoride as well as for the reaction instead of microwave heating. We furthermore describe solid phase extraction and HPLC procedures for quantitative determination of [{sup 18}F]altanserin and metabolites in plasma. The time course of arterial plasma activity with and without metabolite correction was determined. 90 min after bolus injection, 38.4% of total plasma activity derived from unchanged [{sup 18}F]altanserin. Statistical comparison of kinetic profiles of [{sup 18}F]altanserin metabolism in plasma samples collected in the course of two ongoing studies employing placebo, the serotonin releaser dexfenfluramine and the hallucinogen psilocybin, revealed the same tracer metabolism. We conclude that metabolite analysis for correction of individual plasma input functions used in tracer modeling is not necessary for [{sup 18}F]altanserin studies involving psilocybin or dexfenfluramine treatment.

  6. GMP-compliant radiosynthesis of [18F]altanserin and human plasma metabolite studies

    International Nuclear Information System (INIS)

    Hasler, F.; Kuznetsova, O.F.; Krasikova, R.N.; Cservenyak, T.; Quednow, B.B.; Vollenweider, F.X.; Ametamey, S.M.; Westera, G.

    2009-01-01

    [ 18 F]altanserin is the preferred radiotracer for in-vivo labeling of serotonin 2A receptors by positron emission tomography (PET). We report a modified synthesis procedure suited for reliable production of multi-GBq amounts of [ 18 F]altanserin useful for application in humans. We introduced thermal heating for drying of [ 18 F]fluoride as well as for the reaction instead of microwave heating. We furthermore describe solid phase extraction and HPLC procedures for quantitative determination of [ 18 F]altanserin and metabolites in plasma. The time course of arterial plasma activity with and without metabolite correction was determined. 90 min after bolus injection, 38.4% of total plasma activity derived from unchanged [ 18 F]altanserin. Statistical comparison of kinetic profiles of [ 18 F]altanserin metabolism in plasma samples collected in the course of two ongoing studies employing placebo, the serotonin releaser dexfenfluramine and the hallucinogen psilocybin, revealed the same tracer metabolism. We conclude that metabolite analysis for correction of individual plasma input functions used in tracer modeling is not necessary for [ 18 F]altanserin studies involving psilocybin or dexfenfluramine treatment

  7. Dexamethasone decreases plasma levels of the prochiral fenbendazole and its chiral and achiral metabolites in sheep.

    Science.gov (United States)

    Sánchez, S; Small, J; Jones, D G; McKellar, Q A

    2003-07-01

    1. The effect of co-administration of either short- or long-acting formulations of DXM on hepatic function and the plasma pharmacokinetic behaviour of prochiral fenbendazole (FBZ) and its metabolites was evaluated in sheep. 2. Neither DXM treatment markedly affected any of the biochemical markers of hepatic function tested. In contrast, both formulations significantly modified the plasma pharmacokinetic behaviour of FBZ and its metabolites. 3. Plasma FBZ concentrations and the associated area under the time-concentration curves were significantly lower, although the plasma detection period was longer (72 versus 48 h) in the DXM pretreated animals compared with those given FBZ alone. 4. DXM also appeared to alter the pattern of FBZ absorption, possibly through effects on abomasal pH. The shape of the plasma concentration-time curves for oxfendazole (OFZ) and fenbendazole sulphone (FBZSO(2)) were similar to FBZ, raising the possibility that DXM treatment may have altered the liver biotransformation of the parent drug. 5. The concentrations of the (+) chiral metabolite of OFZ were significantly lower in DXM pretreated animals compared with those given FBZ alone. The trend was similar for the (-) antipode, although the differences between DXM pretreated and non-pretreated animals were not statistically significant.

  8. The effect of casein, hydrolyzed casein and whey proteins on urinary and postprandial plasma metabolites in overweight and moderately obese human subjects

    DEFF Research Database (Denmark)

    Schmedes, Mette S; Bendtsen, Line Quist; Gomes, Sisse

    2018-01-01

    , hydrolyzed casein and whey proteins in overweight and moderately obese men and women by investigating select urinary and blood plasma metabolites. RESULTS: A total of 21 urinary and 23 plasma metabolites were identified by NMR spectroscopy. The postprandial plasma metabolites revealed a significant diet...

  9. Arsenic speciation in hair and nails of acute promyelocytic leukemia (APL) patients undergoing arsenic trioxide treatment.

    Science.gov (United States)

    Chen, Baowei; Cao, Fenglin; Lu, Xiufen; Shen, Shengwen; Zhou, Jin; Le, X Chris

    2018-07-01

    Arsenic in hair and nails has been used to assess chronic exposure of humans to environmental arsenic. However, it remains to be seen whether it is appropriate to evaluate acute exposure to sub-lethal doses of arsenic typically used in therapeutics. In this study, hair, fingernail and toenail samples were collected from nine acute promyelocytic leukemia (APL) patients who were administered intravenously the daily dose of 10 mg arsenic trioxide (7.5 mg arsenic) for up to 54 days. These hair and nail samples were analyzed for arsenic species using high performance liquid chromatography separation and inductively coupled plasma mass spectrometry detection (HPLC-ICPMS). Inorganic arsenite was the predominant form among water-extractable arsenicals. Dimethylarsinic acid (DMA V ), monomethylarsonic acid (MMA V ), monomethylarsonous acid (MMA III ), monomethylmonothioarsonic acid (MMMTA V ), and dimethylmonothioarsinic acid (DMMTA V ) were also detected in both hair and nail samples. This is the first report of the detection of MMA III and MMMTA V as metabolites of arsenic in hair and nails of APL patients. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. [Determination of arsenic speciation in Scomberomorus niphonius by capillary electrophoresis-inductively coupled plasma mass spectrometry].

    Science.gov (United States)

    Chen, Fa-rong; Zheng, Li; Wang, Zhi-Guang; Sun, Jie; Han, Li-Hui; Wang, Xiao-ru

    2014-06-01

    A method for the detection of arsenocholine (AsC), arsenobetaine (AsB), As(III), dimethylarsinic (DMA), monomethylarsonic (MMA) and As (V) by capillary electrophoresis-inductively coupled plasma mass spectrometry (CE-ICP-MS) was established. The results showed that the six species of arsenic were separated within 20 min under the optimized conditions. Good linearities of 6 arsenic species were observed in the range from 2 to 50 μg x L(-1) with the linear correlation greater than 0.996, the detection limits were 0.10-1.08 μg x L(-1) and the RSDs (n = 5) of the peak areas were smaller than 7%. The method was successfully adopted to the determination of the species in Scomberomorus niphonius. The recoveries were between 93% and 98%, and we found the arsenobetaine (AsB) was the main species in the sample. The method was suitable for the analysis of other biological samples with the advantages of good stability, less sample consumption, short analysis time and convenience.

  11. Elevated levels of plasma Big endothelin-1 and its relation to hypertension and skin lesions in individuals exposed to arsenic

    International Nuclear Information System (INIS)

    Hossain, Ekhtear; Islam, Khairul; Yeasmin, Fouzia; Karim, Md. Rezaul; Rahman, Mashiur; Agarwal, Smita; Hossain, Shakhawoat; Aziz, Abdul; Al Mamun, Abdullah; Sheikh, Afzal; Haque, Abedul; Hossain, M. Tofazzal; Hossain, Mostaque; Haris, Parvez I.; Ikemura, Noriaki; Inoue, Kiyoshi; Miyataka, Hideki; Himeno, Seiichiro; Hossain, Khaled

    2012-01-01

    Chronic arsenic (As) exposure affects the endothelial system causing several diseases. Big endothelin-1 (Big ET-1), the biological precursor of endothelin-1 (ET-1) is a more accurate indicator of the degree of activation of the endothelial system. Effect of As exposure on the plasma Big ET-1 levels and its physiological implications have not yet been documented. We evaluated plasma Big ET-1 levels and their relation to hypertension and skin lesions in As exposed individuals in Bangladesh. A total of 304 study subjects from the As-endemic and non-endemic areas in Bangladesh were recruited for this study. As concentrations in water, hair and nails were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The plasma Big ET-1 levels were measured using a one-step sandwich enzyme immunoassay kit. Significant increase in Big ET-1 levels were observed with the increasing concentrations of As in drinking water, hair and nails. Further, before and after adjusting with different covariates, plasma Big ET-1 levels were found to be significantly associated with the water, hair and nail As concentrations of the study subjects. Big ET-1 levels were also higher in the higher exposure groups compared to the lowest (reference) group. Interestingly, we observed that Big ET-1 levels were significantly higher in the hypertensive and skin lesion groups compared to the normotensive and without skin lesion counterpart, respectively of the study subjects in As-endemic areas. Thus, this study demonstrated a novel dose–response relationship between As exposure and plasma Big ET-1 levels indicating the possible involvement of plasma Big ET-1 levels in As-induced hypertension and skin lesions. -- Highlights: ► Plasma Big ET-1 is an indicator of endothelial damage. ► Plasma Big ET-1 level increases dose-dependently in arsenic exposed individuals. ► Study subjects in arsenic-endemic areas with hypertension have elevated Big ET-1 levels. ► Study subjects with arsenic

  12. Elevated levels of plasma Big endothelin-1 and its relation to hypertension and skin lesions in individuals exposed to arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Hossain, Ekhtear; Islam, Khairul; Yeasmin, Fouzia [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi-6205 (Bangladesh); Karim, Md. Rezaul [Department of Applied Nutrition and Food Technology, Islamic University, Kushtia-7003 (Bangladesh); Rahman, Mashiur; Agarwal, Smita; Hossain, Shakhawoat; Aziz, Abdul; Al Mamun, Abdullah; Sheikh, Afzal; Haque, Abedul; Hossain, M. Tofazzal [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi-6205 (Bangladesh); Hossain, Mostaque [Department of Medicine, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM), Dhaka (Bangladesh); Haris, Parvez I. [Faculty of Health and Life Sciences, De Montfort University, Leicester, LE1 9BH (United Kingdom); Ikemura, Noriaki; Inoue, Kiyoshi; Miyataka, Hideki; Himeno, Seiichiro [Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770–8514 (Japan); Hossain, Khaled, E-mail: khossain69@yahoo.com [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi-6205 (Bangladesh)

    2012-03-01

    Chronic arsenic (As) exposure affects the endothelial system causing several diseases. Big endothelin-1 (Big ET-1), the biological precursor of endothelin-1 (ET-1) is a more accurate indicator of the degree of activation of the endothelial system. Effect of As exposure on the plasma Big ET-1 levels and its physiological implications have not yet been documented. We evaluated plasma Big ET-1 levels and their relation to hypertension and skin lesions in As exposed individuals in Bangladesh. A total of 304 study subjects from the As-endemic and non-endemic areas in Bangladesh were recruited for this study. As concentrations in water, hair and nails were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The plasma Big ET-1 levels were measured using a one-step sandwich enzyme immunoassay kit. Significant increase in Big ET-1 levels were observed with the increasing concentrations of As in drinking water, hair and nails. Further, before and after adjusting with different covariates, plasma Big ET-1 levels were found to be significantly associated with the water, hair and nail As concentrations of the study subjects. Big ET-1 levels were also higher in the higher exposure groups compared to the lowest (reference) group. Interestingly, we observed that Big ET-1 levels were significantly higher in the hypertensive and skin lesion groups compared to the normotensive and without skin lesion counterpart, respectively of the study subjects in As-endemic areas. Thus, this study demonstrated a novel dose–response relationship between As exposure and plasma Big ET-1 levels indicating the possible involvement of plasma Big ET-1 levels in As-induced hypertension and skin lesions. -- Highlights: ► Plasma Big ET-1 is an indicator of endothelial damage. ► Plasma Big ET-1 level increases dose-dependently in arsenic exposed individuals. ► Study subjects in arsenic-endemic areas with hypertension have elevated Big ET-1 levels. ► Study subjects with arsenic

  13. Profiling of plasma metabolites in canine oral melanoma using gas chromatography-mass spectrometry.

    Science.gov (United States)

    Kawabe, Mifumi; Baba, Yuta; Tamai, Reo; Yamamoto, Ryohei; Komori, Masayuki; Mori, Takashi; Takenaka, Shigeo

    2015-08-01

    Malignant melanoma is one of the most common and aggressive tumors in the oral cavity of dog. The tumor has a poor prognosis, and methods for diagnosis and prediction of prognosis after treatment are required. Here, we examined metabolite profiling using gas chromatography-mass spectrometry (GC-MS) for development of a discriminant model for evaluation of prognosis. Metabolite profiles were evaluated in healthy and melanoma plasma samples using orthogonal projection to latent structure using discriminant analysis (OPLS-DA). Cases that were predicted to be healthy using the OPLS discriminant model had no advanced lesions after radiation therapy. These results indicate that metabolite profiling may be useful in diagnosis and prediction of prognosis of canine malignant melanoma.

  14. Association of plasma IL-6 and Hsp70 with HRV at different levels of PAHs metabolites.

    Directory of Open Access Journals (Sweden)

    Jian Ye

    Full Text Available Exposure to polycyclic aromatic hydrocarbons (PAHs is associated with reduced heart rate variability (HRV, a strong predictor of cardiovascular diseases, but the mechanism is not well understood.We hypothesized that PAHs might induce systemic inflammation and stress response, contributing to altered cardiac autonomic function.HRV indices were measured using a 3-channel digital Holter monitor in 800 coke oven workers. Plasma levels of interleukin-6 (IL-6 and heat shock protein 70 (Hsp70 were determined using ELISA. Twelve urinary PAHs metabolites (OH-PAHs were measured by gas chromatography-mass spectrometry.We found that significant dose-dependent relationships between four urinary OH-PAHs and IL-6 (all Ptrend<0.05; and an increase in quartiles of IL-6 was significantly associated with a decrease in total power (TP and low frequency (LF (Ptrend = 0.014 and 0.006, respectively. In particular, elevated IL-6 was associated in a dose-dependent manner with decreased TP and LF in the high-PAHs metabolites groups (all Ptrend<0.05, but not in the low-PAHs metabolites groups. No significant association between Hsp70 and HRV in total population was found after multivariate adjustment. However, increased Hsp70 was significantly associated with elevated standard deviation of NN intervals (SDNN, TP and LF in the low-PAHs metabolites groups (all Ptrend<0.05. We also observed that both IL-6 and Hsp70 significantly interacted with multiple PAHs metabolites in relation to HRV.In coke oven workers, increased IL-6 was associated with a dose-response decreased HRV in the high-PAHs metabolites groups, whereas increase of Hsp70 can result in significant dose-related increase in HRV in the low-PAHs metabolites groups.

  15. A new metabolic pathway of arsenite: arsenic-glutathione complexes are substrates for human arsenic methyltransferase Cyt19

    Energy Technology Data Exchange (ETDEWEB)

    Hayakawa, Toru [National Institute for Environmental Studies, Environmental Health Sciences Division, Ibaraki (Japan); Chiba University, Faculty of Pharmaceutical Sciences, Chiba (Japan); Kobayashi, Yayoi; Cui, Xing; Hirano, Seishiro [National Institute for Environmental Studies, Environmental Health Sciences Division, Ibaraki (Japan)

    2005-04-01

    The metabolism of arsenic is generally accepted to proceed by repetitive reduction and oxidative methylation; the latter is mediated by arsenic methyltransferase (Cyt19). In human urine, the major metabolites of inorganic arsenicals such as arsenite (iAs{sup III}) and arsenate (iAs{sup V}) are monomethylarsonic acid (MMA{sup V}) and dimethylarsinic acid (DMA{sup V}). On the other hand, in rat bile, the major metabolites of iAs{sup III} have been reported to be arsenic-glutathione (As-GSH) complexes. In the present study we investigate whether these As-GSH complexes are substrates for arsenic methyltransferase by using human recombinant Cyt19. Analyses by high-performance liquid chromatography-inductively coupled plasma mass spectrometry suggested that arsenic triglutathione (ATG) was generated nonenzymatically from iAs{sup III} when GSH was present at concentrations 2 mM or higher. Human recombinant Cyt19 catalyzed transfer of a methyl group from S-adenosyl-l-methionine to arsenic and produced monomethyl and dimethyl arsenicals. The methylation of arsenic was catalyzed by Cyt19 only when ATG was present in the reaction mixture. Moreover, monomethylarsonic diglutathione (MADG) was a substrate of Cyt19 for further methylation to dimethylarsinic glutathione (DMAG). On the other hand, monomethylarsonous acid (MMA{sup III}), a hydrolysis product of MADG, was not methylated to dimethyl arsenical by Cyt19. These results suggest that As-GSH complexes such as ATG and MADG were converted by Cyt19 to MADG and DMAG, respectively. Both MADG and DMAG were unstable in solution when the GSH concentration was lower than 1 mM, and were hydrolyzed and oxidized to MMA{sup V} and DMA{sup V}, respectively. Metabolism of iAs{sup III} to methylated arsenicals by Cyt19 was via ATG and MADG rather than by oxidative methylation of iAs{sup III} and MMA{sup III}. (orig.)

  16. Chiral Plasma Pharmacokinetics of 3,4-Methylenedioxymethamphetamine and its Phase I and II Metabolites following Controlled Administration to Humans.

    OpenAIRE

    Steuer Andrea E; Schmidhauser Corina; Schmid Yasmin; Rickli Anna; Liechti Matthias E; Kraemer Thomas

    2015-01-01

    Generally, pharmacokinetic studies on 3,4-methylenedioxymethamphetamine (MDMA) in blood have been performed after conjugate cleavage, without taking into account that phase II metabolites represent distinct chemical entities with their own effects and stereoselective pharmacokinetics. The aim of the present study was to stereoselectively investigate the pharmacokinetics of intact glucuronide and sulfate metabolites of MDMA in blood plasma after a controlled single MDMA dose. Plasma samples fr...

  17. Arsenic Metabolism in Children Differs From That in Adults.

    Science.gov (United States)

    Skröder Löveborn, Helena; Kippler, Maria; Lu, Ying; Ahmed, Sultan; Kuehnelt, Doris; Raqib, Rubhana; Vahter, Marie

    2016-07-01

    Arsenic toxicity in adults is associated with methylation efficiency, influenced by factors such as gender, genetics, and nutrition. The aim of this study was to evaluate influencing factors for arsenic metabolism in children. For 488 children (9 years), whose mothers participated in a study on arsenic exposure during pregnancy (nested into the MINIMat trial) in rural Bangladesh, we measured urinary concentrations of inorganic arsenic (iAs) and its metabolites methylarsonic acid (MMA) and dimethylarsinic acid (DMA) by HPLC-HG-ICPMS. Methylation efficiency was assessed by relative amounts (%) of the metabolites. We evaluated the impact of factors such as maternal urinary metabolite pattern, arsenic exposure, gender, socioeconomic status, season of sampling, and nutritional factors, including erythrocyte selenium (Ery-Se), and plasma folate and vitamin B12.Children had higher %DMA and lower %iAs in urine compared to their mothers, unrelated to their lower exposure [median urinary arsenic (U-As) 53 vs 78 µg/l]. Surprisingly, selenium status (Ery-Se) was strongly associated with children's arsenic methylation; an increase in Ery-Se from the 5-95th percentile was associated with: +1.8 percentage points (pp) for %iAs (P  =  .001), +1.4 pp for %MMA (P  =  .003), and -3.2 pp for %DMA (P  41 µg/l, P  =  .026). As expected, plasma folate was inversely associated with %iAs (5-95th percentile: -1.9 pp, P  =  .001) and positively associated with %DMA (5-95th percentile: +2.2 pp, P  =  .008). Children methylated arsenic more efficiently than their mothers. Also influencing factors, mainly selenium and folate, differed. This warrants further research. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

  18. Plasma metabolite score correlates with Hypoxia time in a newly born piglet model for asphyxia

    Directory of Open Access Journals (Sweden)

    Julia Kuligowski

    2017-08-01

    Full Text Available Hypoxic-ischemic encephalopathy (HIE secondary to perinatal asphyxia is a leading cause of mortality and acquired long-term neurologic co-morbidities in the neonate. The most successful intervention for the treatment of moderate to severe HIE is moderate whole body hypothermia initiated within 6 h from birth. The objective and prompt identification of infants who are at risk of developing moderate to severe HIE in the critical first hours still remains a challenge. This work proposes a metabolite score calculated based on the relative intensities of three metabolites (choline, 6,8-dihydroxypurine and hypoxanthine that showed maximum correlation with hypoxia time in a consolidated piglet model for neonatal hypoxia-ischemia. The metabolite score's performance as a biomarker for perinatal hypoxia and its usefulness for clinical grading and decision making have been assessed and compared to the performance of lactate which is currently considered the gold standard. For plasma samples withdrawn before and directly after a hypoxic insult, the metabolite score performed similar to lactate. However, it provided an enhanced predictive capacity at 2 h after resuscitation. The present study evidences the usefulness of the metabolite score for improving the early assessment of the severity of the hypoxic insult based on serial determinations in a minimally invasive biofluid. The applicability of the metabolite score for clinical diagnosis and patient stratification for hypothermia treatment has to be confirmed in multicenter trials involving newborns suffering from HIE. Keywords: Hypoxia, Perinatal asphyxia, Newborn, Metabolic biomarker, Neonatal piglet model, Liquid Chromatography – Time-of-Flight Mass Spectrometry (LC-TOF-MS

  19. Milk decreases urinary excretion but not plasma pharmacokinetics of cocoa flavan-3-ol metabolites in humans.

    Science.gov (United States)

    Mullen, William; Borges, Gina; Donovan, Jennifer L; Edwards, Christine A; Serafini, Mauro; Lean, Michael E J; Crozier, Alan

    2009-06-01

    Cocoa drinks containing flavan-3-ols are associated with many health benefits, and conflicting evidence exists as to whether milk adversely affects the bioavailability of flavan-3-ols. The objective was to determine the effect of milk on the bioavailability of cocoa flavan-3-ol metabolites. Nine human volunteers followed a low-flavonoid diet for 2 d before drinking 250 mL of a cocoa beverage, made with water or milk, that contained 45 micromol (-)-epicatechin and (-)-catechin. Plasma and urine samples were collected for 24 h, and flavan-3-ol metabolites were analyzed by HPLC with photodiode array and mass spectrometric detection. Milk affected neither gastric emptying nor the transit time through the small intestine. Two flavan-3-ol metabolites were detected in plasma and 4 in urine. Milk had only minor effects on the plasma pharmacokinetics of an (epi)catechin-O-sulfate and had no effect on an O-methyl-(epi)catechin-O-sulfate. However, milk significantly lowered the excretion of 4 urinary flavan-3-ol metabolites from 18.3% to 10.5% of the ingested dose (P = 0.016). Studies that showed protective effects of cocoa and those that showed no effect of milk on bioavailability used products that have a much higher flavan-3-ol content than does the commercial cocoa used in the present study. Most studies of the protective effects of cocoa have used drinks with a very high flavan-3-ol content. Whether similar protective effects are associated with the consumption of many commercial chocolate and cocoa products containing substantially lower amounts of flavan-3-ols, especially when absorption at lower doses is obstructed by milk, remains to be determined.

  20. Plasma Levels of Biotin Metabolites Are Elevated in Hemodialysis Patients with Cramps.

    Science.gov (United States)

    Fujiwara, Masako; Ando, Itiro; Yagi, Shigeaki; Nishizawa, Manabu; Oguma, Shiro; Satoh, Keisuke; Sato, Hiroshi; Imai, Yutaka

    2016-08-01

    Patients with renal failure undergoing hemodialysis (HD) are susceptible to muscle cramps during and after HD. Muscle cramps are defined as the sudden onset of a prolonged involuntary muscle contraction accompanied by severe pain. Through HD, water-soluble vitamins are drawn out with water. Since biotin, a water-soluble vitamin, plays an essential role as one of the coenzymes in producing energy, we have hypothesized that deficiency of biotin may be responsible for HD-associated cramps. We previously reported that biotin administration ameliorated the muscle cramps, despite the elevated plasma biotin levels before HD and biotin administration, as judged by an enzyme-linked immunosorbent assay (ELISA). However, the ELISA measures not only biotin but also total avidin-binding substances (TABS) including biotin metabolites. In the present study, we determined biotin in HD patients as well as healthy controls, using a newly developed method with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The plasma samples were collected from 28 HD patients (16 patients with cramps and 12 patients without cramps) before HD and biotin administration and from 11 controls. The results showed that the accumulation of biotin and TABS in plasma of HD patients compared to controls. Importantly, the levels of biotin metabolites, i.e. TABS subtracted by biotin, increased significantly in patients with cramps over those without cramps. Moreover, the levels of biotin metabolites were significantly higher in patients with a poor response to administered biotin, compared to those with a good response. We propose that accumulated biotin metabolites impair biotin's functions as a coenzyme.

  1. Coupling nanoliter high-performance liquid chromatography to inductively coupled plasma mass spectrometry for arsenic speciation.

    Science.gov (United States)

    Cheng, Heyong; Shen, Lihuan; Liu, Jinhua; Xu, Zigang; Wang, Yuanchao

    2018-04-01

    Nanoliter high-performance liquid chromatography shows low consumption of solvents and samples, offering one of the best choices for arsenic speciation in precious samples in combination with inuctively coupled plasma mass spectrometry. A systematic investigation on coupling nanoliter high-performance liquid chromatography to inductively coupled plasma mass spectrometry from instrument design to injected sample volume and mobile phase was performed in this study. Nanoflow mobile phase was delivered by flow splitting using a conventional high-pressure pump with reuse of mobile phase waste. Dead volume was minimized to 60 nL for the sheathless interface based on the previously developed nanonebulizer. Capillary columns for nanoliter high-performance liquid chromatography were found to be sensitive to sample loading volume. An apparent difference was also found between the mobile phases for nanoliter and conventional high-performance liquid chromatography. Baseline separation of arsenite, arsenate, monomethylarsenic, and dimethylarsenic was achieved within 11 min on a 15 cm C 18 capillary column and within 12 min on a 25 cm strong anion exchange column. Detection limits of 0.9-1.8 μg/L were obtained with precisions variable in the range of 1.6-4.2%. A good agreement between determined and certified values of a certified reference material of human urine (GBW 09115) validated its accuracy along with good recoveries (87-102%). © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. [Determination of five arsenic species in rice by liquid chromatography-inductively coupled plasma-mass spectrometry].

    Science.gov (United States)

    Gong, Jiadi; Cao, Xiaolin; Cao, Zhaoyun; Bian, Yingfang; Yu, Shasha; Chen, Mingxue

    2014-07-01

    A method was developed for the simultaneous determination of arsenic acid [As (V)], arsenious acid [As (III)], arsenobetaine (AsB), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in rice by liquid chromatography-inductively coupled plasma-mass spectrometry (LC-ICP-MS). The extraction reagent was 0.3 mol/L nitric acid with heat-assistant condition for 1.5 h at 95 degrees C. Then, the five arsenic species were separated by an anion exchange column (Dionex IonPac AS19, 250 mm x 4 mm) and detected by ICP-MS. Four kinds of extracted solutions were compared through the extraction efficiency. The concentration of nitric acid, the temperature and the extraction time were optimized. The recoveries of the five arsenic species spiked in rice at two levels ranged from 89.6% to 99.5% with the relative standard deviations (RSDs, n = 5) of 0.6% - 3.6%. The measured values of the arsenic species in standard rice materials were consistent with their standard values. The linear ranges were 0.05 - 200 microg/L for AsB and DMA, 0.10-400 microg/L for As (III) and MMA, 0.15-600 microg/L for As (V). The limits of detection for the five arsenic species were 0.15-0.45 microg/kg. The results showed that the method is much more precise for the risk assessment of the rice. This method is simple, accurate and durable for the determination of arsenic species in rice.

  3. Effects of vanadium supplementation on performance, some plasma metabolites and glucose metabolism in Mahabadi goat kids.

    Science.gov (United States)

    Zarqami, A; Ganjkhanlou, M; Zali, A; Rezayazdi, K; Jolazadeh, A R

    2018-04-01

    This experiment was conducted to investigate the effects of vanadium (V) supplementation on performance, some plasma metabolites (cholesterol and triglycerides) and glucose metabolism in Mahabadi goat kids. Twenty-eight male kids (15 ± 2 kg body weight) were fed for 14 weeks in a completely randomized design with four treatments. Treatments were supplemented with 0 (control), 1, 2, and 3 mg V as vanadyl sulfate/animal/daily. On day 70, an intravenous glucose tolerance test (IVGTT) was conducted. Dry matter intake did not change by V supplementation, but adding V quadraticaly improved feed efficiency (p = .03) and tended to increase average daily gain (Quadratic, p = .09). Blood metabolites were unaffected by V supplementation, except for concentration of glucose in plasma, which decreased linearly as supplemental V level increased (p = .02). Plasma glucose concentrations at 15, 30, 45 and 60 min after glucose infusion were decreased in a quadratic fashion in response to increasing supplemental V level (p kids supplemented with 2 mg V had higher glucose clearance rate (K) and lower glucose half-life (T ½ ; p kids. © 2017 Blackwell Verlag GmbH.

  4. Determination of hexamethylmelamine and metabolites in plasma or serum by gas—liquid chromatography with a nitrogen-sensitive detector

    NARCIS (Netherlands)

    Hulshoff, A.; Neijt, J.P.; Smulders, C.F.A.; Loenen, A.C. van; Pinedo, H.M.

    1980-01-01

    A gas chromatographic method for the quantitative determination of hexamethylmelamine (HMM) and five of its metabolites in plasma (or serum) is described. After adjustment of the pH of the plasma sample to about 9.5, the compounds are extracted with chloroform containing 5% of isopropanol. Amyl

  5. Citalopram and escitalopram plasma drug and metabolite concentrations: genome-wide associations.

    Science.gov (United States)

    Ji, Yuan; Schaid, Daniel J; Desta, Zeruesenay; Kubo, Michiaki; Batzler, Anthony J; Snyder, Karen; Mushiroda, Taisei; Kamatani, Naoyuki; Ogburn, Evan; Hall-Flavin, Daniel; Flockhart, David; Nakamura, Yusuke; Mrazek, David A; Weinshilboum, Richard M

    2014-08-01

    Citalopram (CT) and escitalopram (S-CT) are among the most widely prescribed selective serotonin reuptake inhibitors used to treat major depressive disorder (MDD). We applied a genome-wide association study to identify genetic factors that contribute to variation in plasma concentrations of CT or S-CT and their metabolites in MDD patients treated with CT or S-CT. Our genome-wide association study was performed using samples from 435 MDD patients. Linear mixed models were used to account for within-subject correlations of longitudinal measures of plasma drug/metabolite concentrations (4 and 8 weeks after the initiation of drug therapy), and single-nucleotide polymorphisms (SNPs) were modelled as additive allelic effects. Genome-wide significant associations were observed for S-CT concentration with SNPs in or near the CYP2C19 gene on chromosome 10 (rs1074145, P = 4.1 × 10(-9) ) and with S-didesmethylcitalopram concentration for SNPs near the CYP2D6 locus on chromosome 22 (rs1065852, P = 2.0 × 10(-16) ), supporting the important role of these cytochrome P450 (CYP) enzymes in biotransformation of citalopram. After adjustment for the effect of CYP2C19 functional alleles, the analyses also identified novel loci that will require future replication and functional validation. In vitro and in vivo studies have suggested that the biotransformation of CT to monodesmethylcitalopram and didesmethylcitalopram is mediated by CYP isozymes. The results of our genome-wide association study performed in MDD patients treated with CT or S-CT have confirmed those observations but also identified novel genomic loci that might play a role in variation in plasma levels of CT or its metabolites during the treatment of MDD patients with these selective serotonin reuptake inhibitors. © 2014 The British Pharmacological Society.

  6. Arsenic speciation analysis of urine samples from individuals living in an arsenic-contaminated area in Bangladesh.

    Science.gov (United States)

    Hata, Akihisa; Yamanaka, Kenzo; Habib, Mohamed Ahsan; Endo, Yoko; Fujitani, Noboru; Endo, Ginji

    2012-05-01

    Chronic inorganic arsenic (iAs) exposure currently affects tens of millions of people worldwide. To accurately determine the proportion of urinary arsenic metabolites in residents continuously exposed to iAs, we performed arsenic speciation analysis of the urine of these individuals and determined whether a correlation exists between the concentration of iAs in drinking water and the urinary arsenic species content. The subjects were 165 married couples who had lived in the Pabna District in Bangladesh for more than 5 years. Arsenic species were measured using high-performance liquid chromatography and inductively coupled plasma mass spectrometry. The median iAs concentration in drinking water was 55 μgAs/L (range 47.9-153.4 μgAs/L), respectively. No arsenobetaine or arsenocholine was detected. The concentrations of the 4 urinary arsenic species were significantly and linearly related to each other. The urinary concentrations of total arsenic and each species were significantly correlated with the iAs concentration of drinking water. All urinary arsenic species are well correlated with each other and with iAs in drinking water. The most significant linear relationship existed between the iAs concentration in drinking water and urinary iAs + MMA concentration. From these results, combined with the effects of seafood ingestion, the best biomarker of iAs exposure is urinary iAs + MMA concentration.

  7. Evolution of arsenic in high fluence plasma immersion ion implanted silicon: Behavior of the as-implanted surface

    Energy Technology Data Exchange (ETDEWEB)

    Vishwanath, V. [Applied Materials, 3225 Oakmead Village Drive, Santa Clara, CA 95052 (United States); Demenev, E. [Center for Materials and Microsystems, Fondazione Bruno Kessler, Via Sommarive 18, 38123 Povo, Trento (Italy); Department of Molecular Science and Nanosystems, Ca’Foscari University, Dorsoduro 2137, 30123 Venice (Italy); Giubertoni, D., E-mail: giuberto@fbk.eu [Center for Materials and Microsystems, Fondazione Bruno Kessler, Via Sommarive 18, 38123 Povo, Trento (Italy); Vanzetti, L. [Center for Materials and Microsystems, Fondazione Bruno Kessler, Via Sommarive 18, 38123 Povo, Trento (Italy); Koh, A.L. [Stanford Nanocharacterization Laboratory, Stanford University, 476 Lomita Mall, Stanford, CA 94305 (United States); Steinhauser, G. [Colorado State University, Environmental and Radiological Health Sciences, Fort Collins, CO 80523 (United States); Leibniz Universität Hannover, Institut für Radioökologie und Strahlenschutz, 30419 Hannover (Germany); Pepponi, G.; Bersani, M. [Center for Materials and Microsystems, Fondazione Bruno Kessler, Via Sommarive 18, 38123 Povo, Trento (Italy); Meirer, F., E-mail: f.meirer@uu.nl [Inorganic Chemistry and Catalysis, Utrecht University, Utrecht 3584 CG (Netherlands); Foad, M.A. [Applied Materials, 3225 Oakmead Village Drive, Santa Clara, CA 95052 (United States)

    2015-11-15

    Highlights: • Samples prepared by high fluence, low-energy PIII of AsH{sub 3}{sup +} on Si(1 0 0) were studied. • PIII is of high technological interest for ultra-shallow doping and activation. • We used a multi-technique approach to study the As-implanted surface. • We show that PIII presents a new set of problems that needs to be tackled. • The presented study goes toward understanding the root mechanisms involved. - Abstract: High fluence (>10{sup 15} ions/cm{sup 2}) low-energy (<2 keV) plasma immersion ion implantation (PIII) of AsH{sub 3}{sup +} on (1 0 0) silicon was investigated, with the focus on stability and retention of the dopant. At this dose, a thin (∼3 nm) amorphous layer forms at the surface, which contains about 45% arsenic (As) in a silicon and oxygen matrix. The presence of silicon indicates that the layer is not only a result of deposition, but predominantly ion mixing. High fluence PIII introduces high concentration of arsenic, modifying the stopping power for incoming ions resulting in an increased deposition. When exposed to atmosphere, the arsenic rich layer spontaneously evolves forming arsenolite As{sub 2}O{sub 3} micro-crystals at the surface. The micro-crystal formation was monitored over several months and exhibits typical crystal growth kinetics. At the same time, a continuous growth of native silicon oxide rich in arsenic was observed on the exposed surface, suggesting the presence of oxidation enhancing factors linked to the high arsenic concentration at the surface.

  8. Untargeted metabolomic profiling plasma samples of patients with lung cancer for searching significant metabolites by HPLC-MS method

    Science.gov (United States)

    Dementeva, N.; Ivanova, K.; Kokova, D.; Kurzina, I.; Ponomaryova, A.; Kzhyshkowska, J.

    2017-09-01

    Lung cancer is one of the most common types of cancer leading to death. Consequently, the search and the identification of the metabolites associated with the risk of developing cancer are very valuable. For the purpose, untargeted metabolic profiling of the plasma samples collected from the patients with lung cancer (n = 100) and the control group (n = 100) was conducted. After sample preparation, the plasma samples were analyzed using LC-MS method. Biostatistics methods were applied to pre-process the data for elicitation of dominating metabolites which responded to the difference between the case and the control groups. At least seven significant metabolites were evaluated and annotated. The most part of identified metabolites are connected with lipid metabolism and their combination could be useful for follow-up studies of lung cancer pathogenesis.

  9. Effect of Spirulina supplementation on plasma metabolites in crossbred and purebred Australian Merino lambs

    Directory of Open Access Journals (Sweden)

    A.E.O. Malau-Aduli

    2015-06-01

    Full Text Available The effect of supplementing purebred and crossbred Merino lambs with Arthrospira platensis (Spirulina on plasma metabolite concentrations under pasture-based management system and the influences of sire breed and sex were investigated. A completely randomized experimental design balanced by 4 sire breeds (Merino, White Suffolk, Dorset and Black Suffolk, 3 Spirulina supplementation levels (0, 100 and 200 ml representing the control, low and high, respectively and 2 sexes (ewe and wether lambs was utilised. All lambs had ad libitum access to the basal diet of ryegrass pastures and barley. Lambs in the treatment groups were individually drenched daily with Spirulina prior to being released with the control group of lambs for grazing over a 6-week period following a 3-week adjustment phase. At the start and completion of the feeding trial, blood samples were centrifuged and plasma metabolites measured. Data were analysed with Spirulina supplementation level, sire breed, sex and their second-order interactions fitted as fixed effects and metabolite concentrations as dependent variables. Gamma-glutamyl transferase (GGT concentrations decreased (from 79.40 to 69.25 UI and glucose increased (from 3.81 to 4.19 mmol/L as the level of Spirulina supplementation increased from 0 ml in the control to 200 ml in the high treatment groups (P < 0.05. Lambs supplemented at low Spirulina levels had the highest creatinine concentrations (61.75 μmol/L. Interactions between sex and supplementation level significantly affected glucose, aspartate aminotransferase (AST and Mg concentrations (P < 0.05, while sire breed and supplementation level interactions influenced albumin to globulin (A/G ratio, creatinine and GGT concentrations. It was demonstrated that Spirulina supplementation does not negatively impact lamb health and productivity.

  10. Quantification of Stable Isotope Traces Close to Natural Enrichment in Human Plasma Metabolites Using Gas Chromatography-Mass Spectrometry.

    Science.gov (United States)

    Krämer, Lisa; Jäger, Christian; Trezzi, Jean-Pierre; Jacobs, Doris M; Hiller, Karsten

    2018-02-14

    Currently, changes in metabolic fluxes following consumption of stable isotope-enriched foods are usually limited to the analysis of postprandial kinetics of glucose. Kinetic information on a larger diversity of metabolites is often lacking, mainly due to the marginal percentage of fully isotopically enriched plant material in the administered food product, and hence, an even weaker 13 C enrichment in downstream plasma metabolites. Therefore, we developed an analytical workflow to determine weak 13 C enrichments of diverse plasma metabolites with conventional gas chromatography-mass spectrometry (GC-MS). The limit of quantification was increased by optimizing (1) the metabolite extraction from plasma, (2) the GC-MS measurement, and (3) most importantly, the computational data processing. We applied our workflow to study the catabolic dynamics of 13 C-enriched wheat bread in three human subjects. For that purpose, we collected time-resolved human plasma samples at 16 timepoints after the consumption of 13 C-labeled bread and quantified 13 C enrichment of 12 metabolites (glucose, lactate, alanine, glycine, serine, citrate, glutamate, glutamine, valine, isoleucine, tyrosine, and threonine). Based on isotopomer specific analysis, we were able to distinguish catabolic profiles of starch and protein hydrolysis. More generally, our study highlights that conventional GC-MS equipment is sufficient to detect isotope traces below 1% if an appropriate data processing is integrated.

  11. Quantification of Stable Isotope Traces Close to Natural Enrichment in Human Plasma Metabolites Using Gas Chromatography-Mass Spectrometry

    Science.gov (United States)

    Krämer, Lisa; Jäger, Christian; Jacobs, Doris M.; Hiller, Karsten

    2018-01-01

    Currently, changes in metabolic fluxes following consumption of stable isotope-enriched foods are usually limited to the analysis of postprandial kinetics of glucose. Kinetic information on a larger diversity of metabolites is often lacking, mainly due to the marginal percentage of fully isotopically enriched plant material in the administered food product, and hence, an even weaker 13C enrichment in downstream plasma metabolites. Therefore, we developed an analytical workflow to determine weak 13C enrichments of diverse plasma metabolites with conventional gas chromatography-mass spectrometry (GC-MS). The limit of quantification was increased by optimizing (1) the metabolite extraction from plasma, (2) the GC-MS measurement, and (3) most importantly, the computational data processing. We applied our workflow to study the catabolic dynamics of 13C-enriched wheat bread in three human subjects. For that purpose, we collected time-resolved human plasma samples at 16 timepoints after the consumption of 13C-labeled bread and quantified 13C enrichment of 12 metabolites (glucose, lactate, alanine, glycine, serine, citrate, glutamate, glutamine, valine, isoleucine, tyrosine, and threonine). Based on isotopomer specific analysis, we were able to distinguish catabolic profiles of starch and protein hydrolysis. More generally, our study highlights that conventional GC-MS equipment is sufficient to detect isotope traces below 1% if an appropriate data processing is integrated. PMID:29443915

  12. Quantification of Stable Isotope Traces Close to Natural Enrichment in Human Plasma Metabolites Using Gas Chromatography-Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Lisa Krämer

    2018-02-01

    Full Text Available Currently, changes in metabolic fluxes following consumption of stable isotope-enriched foods are usually limited to the analysis of postprandial kinetics of glucose. Kinetic information on a larger diversity of metabolites is often lacking, mainly due to the marginal percentage of fully isotopically enriched plant material in the administered food product, and hence, an even weaker 13C enrichment in downstream plasma metabolites. Therefore, we developed an analytical workflow to determine weak 13C enrichments of diverse plasma metabolites with conventional gas chromatography-mass spectrometry (GC-MS. The limit of quantification was increased by optimizing (1 the metabolite extraction from plasma, (2 the GC-MS measurement, and (3 most importantly, the computational data processing. We applied our workflow to study the catabolic dynamics of 13C-enriched wheat bread in three human subjects. For that purpose, we collected time-resolved human plasma samples at 16 timepoints after the consumption of 13C-labeled bread and quantified 13C enrichment of 12 metabolites (glucose, lactate, alanine, glycine, serine, citrate, glutamate, glutamine, valine, isoleucine, tyrosine, and threonine. Based on isotopomer specific analysis, we were able to distinguish catabolic profiles of starch and protein hydrolysis. More generally, our study highlights that conventional GC-MS equipment is sufficient to detect isotope traces below 1% if an appropriate data processing is integrated.

  13. Plasma pharmacokinetics of catechin metabolite 4'-O-Me-EGC in healthy humans.

    Science.gov (United States)

    Renouf, Mathieu; Redeuil, Karine; Longet, Karin; Marmet, Cynthia; Dionisi, Fabiola; Kussmann, Martin; Williamson, Gary; Nagy, Kornél

    2011-10-01

    Tea is an infusion of the leaves of the Camellia sinensis plant and is the most widely consumed beverage in the world after water. Green tea contains significant amounts of polyphenol catechins and represents a promising dietary component to maintain health and well-being. Epidemiological studies indicate that polyphenol intake may have potential health benefits, such as, reducing the incidence of coronary heart disease, diabetes and cancer. While bioavailability of green tea bioactives is fairly well understood, some gaps still remain to be filled, especially the identification and quantification of conjugated metabolites in plasma, such as, sulphated, glucuronidated or methylated compounds. In the present study, we aimed to quantify the appearance of green tea catechins in plasma with particular emphasis on their methylated forms. After feeding 400 mL of green tea, 1.25% infusion to 9 healthy subjects, we found significant amounts of EC, EGC and EGCg in plasma as expected. EGC was the most bioavailable catechin, and its methylated form (4'-O-Me-EGC) was also present in quantifiable amounts. Its kinetics followed that of its parent compound. However, the relative amount of the methylated form of EGC was lower than that of the parent compound, an important aspect which, in the literature, has been controversial so far. The quantitative results presented in our study were confirmed by co-chromatography and accurate mass analysis of the respective standards. We show that the relative abundance of 4'-O-Me-EGC is ~40% compared to the parent EGC. 4'-O-Me-EGC is an important metabolite derived from catechin metabolism. Its presence in significant amounts should not be overlooked when assessing human bioavailability of green tea.

  14. Determination and pharmacokinetic properties of arsenic speciation in Xiao-Er-Zhi-Bao-Wan by high-performance liquid chromatography with inductively coupled plasma mass spectrometry.

    Science.gov (United States)

    Han, Xu; Luo, Jiaoyang; Zhou, Wenju; Yang, Shihai; Yang, Meihua

    2016-10-01

    A method of high performance liquid chromatography with a Hamilton PRP-X100 ion-exchange column (250 × 4.1 mm id, 10 μm) coupled to inductively coupled plasma mass spectrometry was employed to generate a full concentration-time profile of arsenic speciation after oral administration. The results exhibited good linearity and revealed that, in the pills, the average arsenic concentration was 10105.4 ± 380.7 mg/kg, and in the water extraction solution, the inorganic As(III) and As(V) concentrations were 220.1 ± 12.6 and 45.5 ± 2.3 mg/kg, respectively. No trace of monomethyl arsenic acid was detected in any of the plasma samples. We then successfully applied the established methodology to examine the pharmacokinetics of arsenic speciation. The resulting data revealed that, after oral administration in rats, the plasma concentration of each arsenic species reached C max shortly after initial dosing, and that the distribution and elimination of As(V) was faster than that of As(III) and dimethyl arsenic acid. Additionally, the t 1/2 values of As(V), As(III), and dimethyl arsenic acid were 3.4 ± 1.6, 14.3 ± 4.0, and 19.9 ± 1.6 h, respectively. This study provides references for the determination of arsenic speciation in mineral-containing medicines and could serve as a useful tool in measuring the true toxicity in traditional medicines that contain them. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Protein precipitation: an expedient procedure for the routine analysis of the plasma metabolites of [123I]IBZM

    International Nuclear Information System (INIS)

    Zea-Ponce, Yolanda; Laruelle, Marc

    1999-01-01

    Plasma metabolite analysis of the single photon emission computed tomography (SPECT) D 2 /D 3 receptor radiotracer (S)(-)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-hydroxy-3-[ 123 I] iodo-6-methoxyb enzamide ([ 123 I]IBZM) is needed for the equilibrium analysis of the SPECT data, in brain imaging studies involving bolus plus constant infusion paradigm. The purpose of these experiments was to find an appropriate procedure to expedite this analysis during routine determinations. The procedure was applied to the plasma analysis of 22 human subjects. Each plasma sample was subjected to acetonitrile protein precipitation. After separation of the pellet, the acetonitrile fraction contained 91%±2% (n=88) of the mixture of labeled metabolites and parent compound. The recovery coefficient of unmetabolized [ 123 I]IBZM determined with an standard plasma sample was 95%±2% (n=22). The percent parent compound present in the extracted fraction, measured by high performance liquid chromatography, was 16%±9% (n=85) and the percent metabolites was 84%±9% (n=85). Free fraction determination (f 1 , fraction of radiotracer unbound to protein), was 4%±0.8% (n=22). Free fraction of parent was 15%±8% (n=85). The results indicate that acetonitrile protein precipitation is an adequate method for the analysis of the [ 123 I]IBZM plasma metabolites

  16. Hepatitis C virus infection influences the S-methadone metabolite plasma concentration.

    Directory of Open Access Journals (Sweden)

    Shiow-Ling Wu

    Full Text Available Heroin-dependent patients typically contract hepatitis C virus (HCV at a disproportionately high level due to needle exchange. The liver is the primary target organ of HCV infection and also the main organ responsible for drug metabolism. Methadone maintenance treatment (MMT is a major treatment regimen for opioid dependence. HCV infection may affect methadone metabolism but this has rarely been studied. In our current study, we aimed to test the hypothesis that HCV may influence the methadone dosage and its plasma metabolite concentrations in a MMT cohort from Taiwan.A total of 366 MMT patients were recruited. The levels of plasma hepatitis B virus (HBV, HCV, human immunodeficiency virus (HIV antibodies (Ab, liver aspartate aminotransferase (AST and alanine aminotransferase (ALT, as well as methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP were measured along with the urine morphine concentration and amphetamine screening.Of the 352 subjects in our cohort with HCV test records, 95% were found to be positive for plasma anti-HCV antibody. The liver functional parameters of AST (Wilcoxon Rank-Sum test, P = 0.02 and ALT (Wilcoxon Rank-Sum test, P = 0.04, the plasma methadone concentrations (Wilcoxon Rank-Sum test, P = 0.043 and the R-enantiomer of methadone concentrations (Wilcoxon Rank-Sum test, P = 0.032 were significantly higher in the HCV antibody-positive subjects than in the HCV antibody-negative patients, but not the S-EDDP/methadone dose ratio. The HCV levels correlated with the methadone dose (β= 14.65 and 14.13; P = 0.029 and 0.03 and the S-EDDP/methadone dose ratio (β= -0.41 and -0.40; P = 0.00084 and 0.002 in both univariate and multivariate regression analyses.We conclude that HCV may influence the methadone dose and plasma S-EDDP/methadone dose ratio in MMT patients in this preliminary study.

  17. Aging effect on plasma metabolites and hormones concentrations in riding horses

    Directory of Open Access Journals (Sweden)

    K. Kawasumi

    2015-11-01

    Full Text Available Age effects on plasma metabolites, hormone concentrations, and enzyme activities related to energy metabolism were investigated in 20 riding horses. Animals were divided into two groups: Young (3-8 years and aged (11-18 years. They were clinically healthy, and not obese. Plasma adiponectin (ADN concentrations in aged horses were significantly lower than those in young horses (mean±SE, 6.5±1.3 μg mL-1 vs, 10.9±1.7 μg mL-1, Mann-Whitney U test, respectively; P=0.0233. Plasma non-esterified fatty acid levels and Insulin and malondialdehyde concentrations in aged group tended to increase compared to those in young group although there were not significant differences statistically. In aged group, malate dehydrogenase/lactate dehydrogenase (M/L ratio, which is considered an energy metabolic indicator, did not change significantly compared to that in young group. Present data suggest that aging may negatively affect nutrition metabolism, but not induce remarkable changes in M/L ratio in riding horses.

  18. Analytical artefacts in the speciation of arsenic in clinical samples

    International Nuclear Information System (INIS)

    Slejkovec, Zdenka; Falnoga, Ingrid; Goessler, Walter; Elteren, Johannes T. van; Raml, Reingard; Podgornik, Helena; Cernelc, Peter

    2008-01-01

    Urine and blood samples of cancer patients, treated with high doses of arsenic trioxide were analysed for arsenic species using HPLC-HGAFS and, in some cases, HPLC-ICPMS. Total arsenic was determined with either flow injection-HGAFS in urine or radiochemical neutron activation analysis in blood fractions (in serum/plasma, blood cells). The total arsenic concentrations (during prolonged, daily/weekly arsenic trioxide therapy) were in the μg mL -1 range for urine and in the ng g -1 range for blood fractions. The main arsenic species found in urine were As(III), MA and DMA and in blood As(V), MA and DMA. With proper sample preparation and storage of urine (no preservation agents/storage in liquid nitrogen) no analytical artefacts were observed and absence of significant amounts of alleged trivalent metabolites was proven. On the contrary, in blood samples a certain amount of arsenic can get lost in the speciation procedure what was especially noticeable for the blood cells although also plasma/serum gave rise to some disappearance of arsenic. The latter losses may be attributed to precipitation of As(III)-containing proteins/peptides during the methanol/water extraction procedure whereas the former losses were due to loss of specific As(III)-complexing proteins/peptides (e.g. cysteine, metallothionein, reduced GSH, ferritin) on the column (Hamilton PRP-X100) during the separation procedure. Contemporary analytical protocols are not able to completely avoid artefacts due to losses from the sampling to the detection stage so that it is recommended to be careful with the explanation of results, particularly regarding metabolic and pharmacokinetic interpretations, and always aim to compare the sum of species with the total arsenic concentration determined independently

  19. A rapid monitoring method for inorganic arsenic in rice flour using reversed phase-high performance liquid chromatography-inductively coupled plasma mass spectrometry.

    Science.gov (United States)

    Narukawa, Tomohiro; Chiba, Koichi; Sinaviwat, Savarin; Feldmann, Jörg

    2017-01-06

    A new rapid monitoring method by means of high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) following the heat-assisted extraction was developed for measurement of total inorganic arsenic species in rice flour. As(III) and As(V) eluted at the same retention time and completely separated from organoarsenic species by an isocratic elution program on a reversed phase column. Therefore, neither ambiguous oxidation of arsenite to arsenate nor the integration of two peaks were necessary to determine directly the target analyte inorganic arsenic. Rapid injection allowed measuring 3 replicates within 6min and this combined with a quantitative extraction of all arsenic species from rice flour by a 15min HNO 3 -H 2 O 2 extraction makes this the fastest laboratory based method for inorganic arsenic in rice flour. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Lactate turnover in fast-moving vertebrates: The control of plasma metabolite fluxes

    Energy Technology Data Exchange (ETDEWEB)

    Weber, J.M.

    1987-01-01

    The goals of this thesis were: (1) to investigate the major factors involved in the regulation of plasma metabolite turnover at the whole-organism level-using lactate as a model, and (2) to determine whether endurance-adapted animals can support higher lactate turnover rates than sedentary animals. Lactate turnover was measured by bolus injection of (U{sup {minus}14}C)lacetate in skipjack tuna, Katsuwonus pelamis, and in thoroughbred race horses, Equus caballus. In tuna, turnover rates ranged from 112 to 431 umol min{sup {minus}1} kg{sup {minus}1}, and they were positively correlated with (lactate). These rates were higher than expected for a mammal of equivalent size. Plots of resting lactate and glucose turnover rates vs body mass on a log-log scale were linear for a wide range mammalian body sizes, and they showed the same slope as the classic body mass vs metabolic rate relationship.

  1. A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer.

    Directory of Open Access Journals (Sweden)

    Haojie Li

    2007-03-01

    Full Text Available Vitamin D insufficiency is a common public health problem nationwide. Circulating 25-hydroxyvitamin D3 (25[OH]D, the most commonly used index of vitamin D status, is converted to the active hormone 1,25 dihydroxyvitamin D3 (1,25[OH]2D, which, operating through the vitamin D receptor (VDR, inhibits in vitro cell proliferation, induces differentiation and apoptosis, and may protect against prostate cancer. Despite intriguing results from laboratory studies, previous epidemiological studies showed inconsistent associations of circulating levels of 25(OHD, 1,25(OH2D, and several VDR polymorphisms with prostate cancer risk. Few studies have explored the joint association of circulating vitamin D levels with VDR polymorphisms.During 18 y of follow-up of 14,916 men initially free of diagnosed cancer, we identified 1,066 men with incident prostate cancer (including 496 with aggressive disease, defined as stage C or D, Gleason 7-10, metastatic, and fatal prostate cancer and 1,618 cancer-free, age- and smoking-matched control participants in the Physicians' Health Study. We examined the associations of prediagnostic plasma levels of 25(OHD and 1,25(OH2D, individually and jointly, with total and aggressive disease, and explored whether relations between vitamin D metabolites and prostate cancer were modified by the functional VDR FokI polymorphism, using conditional logistic regression. Among these US physicians, the median plasma 25(OHD levels were 25 ng/ml in the blood samples collected during the winter or spring and 32 ng/ml in samples collected during the summer or fall. Nearly 13% (summer/fall to 36% (winter/spring of the control participants were deficient in 25(OHD (<20 ng/ml and 51% (summer/fall and 77% (winter/spring had insufficient plasma 25(OHD levels (<32 ng/ml. Plasma levels of 1,25(OH2D did not vary by season. Men whose levels for both 25(OHD and 1,25(OH2D were below (versus above the median had a significantly increased risk of aggressive

  2. Urine and plasma metabolites predict the development of diabetic nephropathy in individuals with Type 2 diabetes mellitus

    NARCIS (Netherlands)

    Pena, M. J.; Lambers Heerspink, H. J.; Hellemons, M. E.; Friedrich, T.; Dallmann, G.; Lajer, M.; Bakker, S. J. L.; Gansevoort, R. T.; Rossing, P.; de Zeeuw, D.; Roscioni, S. S.

    Aims Early detection of individuals with Type 2 diabetes mellitus or hypertension at risk for micro- or macroalbuminuria may facilitate prevention and treatment of renal disease. We aimed to discover plasma and urine metabolites that predict the development of micro-or macroalbuminuria. Methods

  3. Identification of 4-hydroxyheptachlorostyrene in polar bear plasma and its binding affinity to transhyretin: a metabolite of octachlorostyrene

    NARCIS (Netherlands)

    Sandau, C.D.; Meerts, I.A.T.M.; Letcher, R.J.; McAlee, A.J.; Chittim, B.; Brouwer, A.; Norstrom, R.J.

    2000-01-01

    A new compound, 4-hydroxyheptachlorostyrene (4-OH-HpCS), was identified as a major component in the chlorinated phenolic compound fraction of polar bear plasma. The structure was hypothesized to be 4-OH-HpCS based on mass spectral interpretation, the assumption that it was a metabolite of

  4. Identification of 4-hydroxyheptachlorostyrene in polar bear plasma and its binding affinity to transthyretin : a metabolite of octachlorostyrene?

    NARCIS (Netherlands)

    Standau, C.D.; Meerts, I.A.T.M.; Letcher, R.J.; McAlees, A.J.; Chittim, B.; Brouwer, A.; Norstrom, R.J.

    2000-01-01

    A new compound, 4-hydroxyheptachlorostyrene (4-OH-HpCS), was identified as a major component in the chlorinated phenolic compound fraction of polar bear plasma. The structure was hypothesized to be 4-OH-HpCS based on mass spectral interpretation, the assumption that it was a metabolite of

  5. Arsenic speciation in saliva of acute promyelocytic leukemia patients undergoing arsenic trioxide treatment

    OpenAIRE

    Chen, Baowei; Cao, Fenglin; Yuan, Chungang; Lu, Xiufen; Shen, Shengwen; Zhou, Jin; Le, X. Chris

    2013-01-01

    Arsenic trioxide has been successfully used as a therapeutic in the treatment of acute promyelocytic leukemia (APL). Detailed monitoring of the therapeutic arsenic and its metabolites in various accessible specimens of APL patients can contribute to improving treatment efficacy and minimizing arsenic-induced side effects. This article focuses on the determination of arsenic species in saliva samples from APL patients undergoing arsenic treatment. Saliva samples were collected from nine APL pa...

  6. Switching antipsychotics to aripiprazole or blonanserin and plasma monoamine metabolites levels in patients with schizophrenia.

    Science.gov (United States)

    Miura, Itaru; Shiga, Tetsuya; Katsumi, Akihiko; Kanno-Nozaki, Keiko; Mashiko, Hirobumi; Niwa, Shin-Ichi; Yabe, Hirooki

    2014-03-01

    Blonanserin is a novel atypical antipsychotic drug that has efficacy equal to risperidone. We investigated the effects of aripiprazole and blonanserin on clinical symptoms and plasma levels of homovanillic acid (pHVA) and 3-methoxy-4hydroxyphenylglycol in the switching strategy of schizophrenia. Twenty two Japanese patients with schizophrenia were enrolled into this open study. The antipsychotics of all patients were switched to aripiprazole or blonanserin for the improvement of clinical symptoms or side effects. Plasma monoamine metabolites levels were analyzed with high-performance liquid chromatography. There were no significant effects for time (p = 0.346) or time × group interaction (p = 0.27) on the changes of positive and negative syndrome scale (PANSS) total score, although blonanserin decreased PANSS scores. We observed negative correlation between pHVA at baseline and the change in PANSS total score (rs = -0.450, p = 0.046). We also found positive correlation between the changes in pHVA and the changes in PANSS total (rs = 0.536, p = 0.015) and positive (rs = 0.572, p = 0.008) scores. There were no differences between blonanserin and aripiprazole in the improvement of clinical symptoms. Our results suggest that pHVA may be useful indicator for the switching strategy to aripiprazole or blonanserin in schizophrenia. Copyright © 2014 John Wiley & Sons, Ltd.

  7. Correlations between phthalate metabolites in urine, serum, and seminal plasma from young Danish men determined by isotope dilution liquid chromatography tandem mass spectrometry

    DEFF Research Database (Denmark)

    Frederiksen, Hanne; Jørgensen, Niels; Andersson, Anna-Maria

    2010-01-01

    Phthalates are suspected of endocrine disrupting effects. We aimed to develop an analytical method for simultaneous determination of several phthalate metabolites in human urine, serum, and seminal plasma and to study correlations between levels of metabolites in these matrices. Thirteen metaboli......Phthalates are suspected of endocrine disrupting effects. We aimed to develop an analytical method for simultaneous determination of several phthalate metabolites in human urine, serum, and seminal plasma and to study correlations between levels of metabolites in these matrices. Thirteen...... metabolites were determined in samples from 60 young Danish men. Metabolites of common di-ester phthalates were detected in most urine samples. Summed di-(2-ethylhexyl) phthalate (DEHP) metabolites were excreted in urine in the highest amount (median = 91.1 ng/mL), followed by monoethyl phthalate (MEP), mono...

  8. A single-run liquid chromatography mass spectrometry method to quantify neuroactive kynurenine pathway metabolites in rat plasma.

    Science.gov (United States)

    Orsatti, Laura; Speziale, Roberto; Orsale, Maria Vittoria; Caretti, Fulvia; Veneziano, Maria; Zini, Matteo; Monteagudo, Edith; Lyons, Kathryn; Beconi, Maria; Chan, Kelvin; Herbst, Todd; Toledo-Sherman, Leticia; Munoz-Sanjuan, Ignacio; Bonelli, Fabio; Dominguez, Celia

    2015-03-25

    Neuroactive metabolites in the kynurenine pathway of tryptophan catabolism are associated with neurodegenerative disorders. Tryptophan is transported across the blood-brain barrier and converted via the kynurenine pathway to N-formyl-L-kynurenine, which is further degraded to L-kynurenine. This metabolite can then generate a group of metabolites called kynurenines, most of which have neuroactive properties. The association of tryptophan catabolic pathway alterations with various central nervous system (CNS) pathologies has raised interest in analytical methods to accurately quantify kynurenines in body fluids. We here describe a rapid and sensitive reverse-phase HPLC-MS/MS method to quantify L-kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxy-L-kynurenine (3HK) and anthranilic acid (AA) in rat plasma. Our goal was to quantify these metabolites in a single run; given their different physico-chemical properties, major efforts were devoted to develop a chromatography suitable for all metabolites that involves plasma protein precipitation with acetonitrile followed by chromatographic separation by C18 RP chromatography, detected by electrospray mass spectrometry. Quantitation range was 0.098-100 ng/ml for 3HK, 9.8-20,000 ng/ml for KYN, 0.49-1000 ng/ml for KYNA and AA. The method was linear (r>0.9963) and validation parameters were within acceptance range (calibration standards and QC accuracy within ±30%). Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Plasma levels of catecholamine metabolites predict the response to sulpiride or fluvoxamine in major depression.

    Science.gov (United States)

    Ueda, N; Yoshimura, R; Shinkai, K; Nakamura, J

    2002-09-01

    We investigated the relationships between the changes in plasma catecholamine metabolites obtained from depressed patients before and after administration of sulpiride, a benzamide compound, or fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), and between clinical responses to treatment with each of these drugs. Responders to sulpiride had significantly lower plasma homovanillic acid (pHVA) levels before administration of sulpiride than did non-responders or controls (responders: 4.5 +/- 3.1 ng/ml, non-responders: 11.1 +/- 5.9 ng/ml, controls: 10.9 +/- 5.3 ng/ml). Positive relationships were observed between changes in pHVA levels and improvement rates in the 17-item Hamilton Depression Rating Scale (Ham-D). In contrast, responders to fluvoxamine had significantly higher plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) levels before administration of fluvoxamine than did non-responders or controls (responders: 8.5 +/- 1.8 ng/ml, non-responders: 5.9 +/- 2.I ng/ml, controls: 5.2 +/- 2.9 ng/ml). Negative relationships were observed between changes in pMHPG levels and improvement rates in Ham-D. These results suggest that lower pretreatment pHVA levels and higher pretreatment levels of pMHPG might be predictors of response to sulpiride and fluvoxamine, respectively, and that sulpiride might produce a functional increase in the dopaminergic system, resulting in improvement in some depressive symptoms; fluvoxamine, on the other hand, might produce a functional decrease in the noradrenergic system via serotonergic neurons, resulting in improvement of those symptoms.

  10. Determination of the 4-monohydroxy metabolites of perhexiline in human plasma, urine and liver microsomes by liquid chromatography.

    Science.gov (United States)

    Davies, Benjamin J; Herbert, Megan K; Coller, Janet K; Somogyi, Andrew A; Milne, Robert W; Sallustio, Benedetta C

    2006-11-07

    The use of perhexiline (PHX) is limited by hepatic and neurological toxicity associated with elevated concentrations in plasma that are the result of polymorphism of the cytochrome P450 2D6 isoform (CYP2D6). PHX is cleared by hepatic oxidation that produces three 4-monohydroxy metabolites: cis-OH-PHX, trans1-OH-PHX and trans2-OH-PHX. The current study describes an HPLC-fluorescent method utilising pre-column derivatization with dansyl chloride. Following derivatization, the metabolites were resolved on a C18 column with a gradient elution using a mobile phase composed of methanol and water. The method described is suitable for the quantification of the metabolites in human plasma and urine following clinical doses and for kinetic studies using human liver microsomes. The method demonstrates sufficient sensitivity, accuracy and precision between 5.0 and 0.01, 50.0 and 0.2 and 1.0 and 0.005 mg/l in human plasma, urine and liver microsomes, respectively, with intra-assay coefficients of variation and bias D6 extensive metaboliser (EM) patients at steady state with respect to PHX dosing determined that the mean (+/-S.D.) renal clearances of trans1-OH-PHX and cis-OH-PHX were 1.58+/-0.35 and 0.16+/-0.06l/h, respectively. The mean (+/-S.D.) dose recovered in urine as free and glucuronidated 4-monohydroxy PHX metabolites was 20.6+/-11.6%.

  11. Determination of Total Arsenic and Speciation in Apple Juice by Liquid Chromatography-Inductively Coupled Plasma Mass Spectrometry: An Experiment for the Analytical Chemistry Laboratory

    Science.gov (United States)

    He, Ping; Colon, Luis A.; Aga, Diana S.

    2016-01-01

    A two-part laboratory experiment was designed for upper-level analytical chemistry students to provide hands-on experience in the use of high performance liquid chromatography (HPLC) for separation and inductively coupled plasma mass spectrometry (ICP-MS) for detection. In the first part of the experiment, the students analyze total arsenic in…

  12. Arsenic speciation using high performance liquid chromatography-inductively coupled plasma-mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Bass, D.A.; Yaeger, J.S.; Crain, J.S.; Kiely, J.T.; Parish, K.J.; Gowdy, M.J. [Argonne National Lab., IL (United States); Mohrman, G.B. [Rocky Mountain Arsenal, Commerce City, CO (United States)

    1995-08-01

    A method has been developed by Argonne National Laboratory to identify and quantify As(III), As(V), and organoarsenic compounds in environmental samples. A arsenic species were separated by reversed-phase, ion-pairing, HPLC using a microbore Inertsil-ODS{trademark} column. Only 1 {micro}L of sample was injected on the column, and the mobile phase flow rates were typically on the order of 40 {micro}L/min. The HPLC mobile phase was a mixture of methanol and tetrabutylammonium hydroxide (TBAH), and the column effluent was introduced into an ICP-mass spectrometer using direct injection nebulization. Detection limits of less than 1 pg As (as injected on the column) were easily obtained for each arsenic species. The effect of changes in mobile phase composition and ICP-MS conditions will be described, as well as quality control measures, e.g., the use of surrogates, internal standards, and matrix spikes. Precision and accuracy information will be presented from the analysis of aqueous standards and soil extracts that were spiked with arsenic oxide [As(III)], sodium arsenate [As(V)], dimethylarsinic acid (DMAA), or chlorovinyl arsenious acid (CVAA). The authors believe that these data demonstrate the utility of this technique for the sensitive determination of arsenic species present in water or soil.

  13. Longitudinal Relationship between Plasma Reactive Oxygen Metabolites and Periodontal Condition in the Maintenance Phase of Periodontal Treatment

    Directory of Open Access Journals (Sweden)

    Tatsuya Machida

    2014-01-01

    Full Text Available Aim. The present cohort study describes the longitudinal relationship between plasma oxidative status and periodontitis progression during the maintenance phase of treatment. Materials and Methods. Forty-five patients (mean age 58.8 years were monitored from 2008 to 2013. Periodontal conditions, including probing pocket depth (PPD and clinical attachment level (CAL, were recorded. Measurements of plasma reactive oxygen metabolites (ROM and biologic antioxidant potential (BAP were performed to evaluate plasma oxidative status. The patients were assigned into 2 groups as low and high plasma ROM level using a cut-off value which was median of plasma ROM level at baseline. Results. In the subjects with low plasma ROM level at baseline, changes in mean CAL were positively correlated with changes in plasma ROM levels, bleeding on probing, and plaque control record, but not with PPD. In the subjects with high plasma ROM at baseline, changes in CAL were significantly associated with only PPD at baseline. On the other hands there were no significant associations between changes in CAL and those in plasma BAP levels. Conclusions. When plasma ROM level in periodontitis patients was low, increases in plasma ROM level were associated with those in CAL during the maintenance phase of treatment.

  14. Correlation of Breastmilk Arsenic With Maternal, Infant Urinary Arsenic and Drinking Water Arsenic in an Arsenic Affected Area of Bangladesh

    Science.gov (United States)

    Alauddin, M.; Islam, M. R.; Milton, A. H.; Alauddin, S. T.; Mouly, T.; Behri, E.; Ayesha, A.; Akter, S.; Islam, M. M.

    2016-12-01

    About 97% of population in Bangladesh depend on groundwater as the principle source of drinking water and this water is highly contaminated with inorganic arsenic. Consumption of arsenic contaminated drinking water by pregnant women raises the prospect of early life exposure to inorganic arsenic for newborn which may be lead to adverse health effect in later life. This work was carried out in parts of Gopalganj district in Bangladesh, a region affected by arsenic contamination in groundwater. The objective of the work was to assess potential early life exposure to arsenic for infants through breastfeeding by mothers who were drinking water with arsenic levels ranging from 100 to 300 µg/l. A cohort of 30 mother-baby pairs were selected for the current study. Breastmilk samples from mothers, urine samples from each pair of subjects at 1, 6 and 9 month age of infant were collected and total arsenic were determined in these samples. In addition speciation of urinary arsenic and metabolites were carried out in 12 mother-baby pairs. Median level for breastmilk arsenic were 0.50 µg/l. Urinary arsenic of infants did not correlate with breastmilk arsenic with progressing age of infants. Maternal and infant urinary total arsenic at 1 month age of infant showed some positive correlation (r = 0.39). In infant urine major metabolite were dimethyl arsenic acid (DMA) (approximately 70%) indicating good methylating capacity for infants at 1 and 6 months of age. In conclusion, infants were not exposed to arsenic through breastfeeding even though mothers were exposed to significant levels of arsenic through drinking water.

  15. [11C]Flumazenil metabolite measurement in plasma is not necessary for accurate brain benzodiazepine receptor quantification

    International Nuclear Information System (INIS)

    Sanabria-Bohorquez, S.M.; Veraart, C.; Labar, D.; Bol, A.; Volder, A.G. de; Michel, C.; Leveque, P.

    2000-01-01

    In this work, a mathematical correction for metabolites has been validated which estimates the relative amount of [ 11 C]flumazenil ([ 11 C]FMZ) in the total plasma curve from the tissue kinetic data without the need for direct metabolite measurement in blood plasma samples. Kinetic data were obtained using a 90-min three-injection protocol on five normal volunteers. First, the relative amount of [ 11 C]FMZ in plasma was modelled by a two-parameter exponential function. The parameters were estimated either directly by fitting this model to the blood plasma metabolite measurements, or indirectly from the simultaneous fitting of tissue time activity curves from several brain regions with a non-linear FMZ kinetic model. Second, the direct and indirect metabolite corrections were fixed and the FMZ compartmental parameters were determined on a regional basis in the brain. The validation was performed by comparing the regional values of benzodiazepine receptor density B max and equilibrium dissociation constant K d obtained with the direct metabolite correction with those values obtained with the indirect correction. For B max , the correlation coefficient r 2 was above 0.97 for all subjects and the slope values of the linear regression were within the interval [0.97, 1.2]. For K d , r 2 was above 0.96, and the slope values of the linear regression were within the interval [0.99, 1.1]. Simulation studies were performed in order to evaluate whether this metabolite correction method could be used in a clinical protocol where only a single [ 11 C]FMZ injection and a linear compartmental model are used. The resulting [ 11 C]FMZ distribution volume estimates were found to be linearly correlated with the true values, with r 2 =1.0 and a slope value of 1.1. The mathematical metabolite correction proved to be a feasible and reliable method to estimate the relative amount of [ 11 C]FMZ in plasma and the compartmental model parameters for three-injection protocols. Although

  16. Arsenic induces structural and compositional colonic microbiome change and promotes host nitrogen and amino acid metabolism

    International Nuclear Information System (INIS)

    Dheer, Rishu; Patterson, Jena; Dudash, Mark; Stachler, Elyse N.; Bibby, Kyle J.; Stolz, Donna B.; Shiva, Sruti; Wang, Zeneng; Hazen, Stanley L.; Barchowsky, Aaron; Stolz, John F.

    2015-01-01

    Chronic exposure to arsenic in drinking water causes cancer and non-cancer diseases. However, mechanisms for chronic arsenic-induced pathogenesis, especially in response to lower exposure levels, are unclear. In addition, the importance of health impacts from xeniobiotic-promoted microbiome changes is just being realized and effects of arsenic on the microbiome with relation to disease promotion are unknown. To investigate impact of arsenic exposure on both microbiome and host metabolism, the stucture and composition of colonic microbiota, their metabolic phenotype, and host tissue and plasma metabolite levels were compared in mice exposed for 2, 5, or 10 weeks to 0, 10 (low) or 250 (high) ppb arsenite (As(III)). Genotyping of colonic bacteria revealed time and arsenic concentration dependent shifts in community composition, particularly the Bacteroidetes and Firmicutes, relative to those seen in the time-matched controls. Arsenic-induced erosion of bacterial biofilms adjacent to the mucosal lining and changes in the diversity and abundance of morphologically distinct species indicated changes in microbial community structure. Bacterical spores increased in abundance and intracellular inclusions decreased with high dose arsenic. Interestingly, expression of arsenate reductase (arsA) and the As(III) exporter arsB, remained unchanged, while the dissimilatory nitrite reductase (nrfA) gene expression increased. In keeping with the change in nitrogen metabolism, colonic and liver nitrite and nitrate levels and ratios changed with time. In addition, there was a concomitant increase in pathogenic arginine metabolites in the mouse circulation. These data suggest that arsenic exposure impacts the microbiome and microbiome/host nitrogen metabolism to support disease enhancing pathogenic phenotypes. - Highlights: • Arsenic exposure induces changes in host and host nitrogen metabolism that cause progresive change in the microbiome. • A polyphasic approach reveals changes

  17. Arsenic induces structural and compositional colonic microbiome change and promotes host nitrogen and amino acid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Dheer, Rishu; Patterson, Jena; Dudash, Mark [Department of Biological Sciences, Duquesne University, Pittsburgh, PA 15282 (United States); Stachler, Elyse N.; Bibby, Kyle J. [Department of Civil and Environmental Engineering, University of Pittsburgh Swanson School of Engineering, Pittsburgh, PA 15261 (United States); Stolz, Donna B. [Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 (United States); Shiva, Sruti [Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh 15261 (United States); Vascular Medicine Institute, University of Pittsburgh, Pittsburgh 15261 (United States); Wang, Zeneng; Hazen, Stanley L. [Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195 (United States); Barchowsky, Aaron, E-mail: aab20@pitt.edu [Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh 15261 (United States); Vascular Medicine Institute, University of Pittsburgh, Pittsburgh 15261 (United States); Department of Environmental and Occupational Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15219 (United States); Stolz, John F. [Department of Biological Sciences, Duquesne University, Pittsburgh, PA 15282 (United States)

    2015-12-15

    Chronic exposure to arsenic in drinking water causes cancer and non-cancer diseases. However, mechanisms for chronic arsenic-induced pathogenesis, especially in response to lower exposure levels, are unclear. In addition, the importance of health impacts from xeniobiotic-promoted microbiome changes is just being realized and effects of arsenic on the microbiome with relation to disease promotion are unknown. To investigate impact of arsenic exposure on both microbiome and host metabolism, the stucture and composition of colonic microbiota, their metabolic phenotype, and host tissue and plasma metabolite levels were compared in mice exposed for 2, 5, or 10 weeks to 0, 10 (low) or 250 (high) ppb arsenite (As(III)). Genotyping of colonic bacteria revealed time and arsenic concentration dependent shifts in community composition, particularly the Bacteroidetes and Firmicutes, relative to those seen in the time-matched controls. Arsenic-induced erosion of bacterial biofilms adjacent to the mucosal lining and changes in the diversity and abundance of morphologically distinct species indicated changes in microbial community structure. Bacterical spores increased in abundance and intracellular inclusions decreased with high dose arsenic. Interestingly, expression of arsenate reductase (arsA) and the As(III) exporter arsB, remained unchanged, while the dissimilatory nitrite reductase (nrfA) gene expression increased. In keeping with the change in nitrogen metabolism, colonic and liver nitrite and nitrate levels and ratios changed with time. In addition, there was a concomitant increase in pathogenic arginine metabolites in the mouse circulation. These data suggest that arsenic exposure impacts the microbiome and microbiome/host nitrogen metabolism to support disease enhancing pathogenic phenotypes. - Highlights: • Arsenic exposure induces changes in host and host nitrogen metabolism that cause progresive change in the microbiome. • A polyphasic approach reveals changes

  18. Evaluation of liquid chromatography inductively coupled plasma mass spectrometry for arsenic speciation in water from industrial treatment of shale

    Energy Technology Data Exchange (ETDEWEB)

    Duarte, Fabio Andrei; Fagundes Pereira, Juliana Severo; Mesko, Marcia Foster; Goldschmidt, Fabiane; Moraes Flores, Erico Marlon de; Dressler, Valderi Luiz, E-mail: valdres@quimica.ufsm.br

    2007-09-15

    This work describes an arsenic speciation analysis in aqueous effluent from a shale industrial plant using liquid chromatography coupled to inductively coupled plasma mass spectrometry (LC-ICP-MS). Arsenic species have been separated through an anion-exchange column and several parameters investigated, such as retention time, pH, flow rate and concentration of the mobile phase (ammonium carbonate), chloride interference and column conditioning time. The best conditions have been found by fixing the pH of the mobile phase at 8.7. Keeping the mobile phase flow rate at 1.5 ml min{sup -1}, arsenic species were separated by varying the concentration of the mobile phase and the time of elution, as follow: 1.5 mmol l{sup -1} for 10 min, 12 mmol l{sup -1} for 10 min and 20 mmol l{sup -1} for 10 min, respectively. Up to 13 As species present in the samples were separated under these conditions and the following species could be identified and quantified: arsenite [As(III)], dimethylarsinic acid (DMA), monomethylarsonic acid (MMA) and arsenate [As(V)]. The limits of detection of the LC-ICP-MS method were 0.02, 0.06, 0.04 and 0.10 {mu}g l{sup -1} of As(III), DMA, MMA, and As(V), respectively. The concentration of these species in the samples were from 3.7 to 6.4 {mu}g l{sup -1}, 6.9 to 13.2 {mu}g l{sup -1}, 100 to 142 {mu}g l{sup -1} and 808 to 1363 {mu}g l{sup -1} for As(III), DMA, MMA and As(V), respectively. The accuracy, evaluated by recovery tests, varied from 94 to 105% and the precision, evaluated by the relative standard deviation was typically lower than 10%.

  19. The influence of feeding and fasting on plasma metabolites in the dogfish shark (Squalus acanthias).

    Science.gov (United States)

    Wood, Chris M; Walsh, Patrick J; Kajimura, Makiko; McClelland, Grant B; Chew, Shit F

    2010-04-01

    Dogfish sharks are opportunistic predators, eating large meals at irregular intervals. Here we present a synthesis of data from several previous studies on responses in plasma metabolites after natural feeding and during prolonged fasting (up to 56days), together with new data on changes in plasma concentrations of amino acids and non-esterified fatty acids. Post-prandial and long-term fasting responses were compared to control sharks fasted for 7days, a typical inter-meal interval. A feeding frenzy was created in which dogfish were allowed to feed naturally on dead teleosts at two consumed ration levels, 2.6% and 5.5% of body weight. Most responses were more pronounced at the higher ration level. These included increases in urea and TMAO concentrations at 20h, followed by stability through to 56days of fasting. Ammonia levels were low and exhibited little short-term response to feeding, but declined to very low values during the extended fast. Glucose and beta-hydroxybutyrate both fell after feeding, the latter to a greater and more prolonged extent (up to 60h), whereas acetoacetate did not change. During prolonged fasting, glucose concentrations were well regulated, but beta-hydroxybutyrate increased to 2-3-fold control levels. Total plasma amino acid concentrations increased in a biphasic fashion, with peaks at 6-20h, and 48-60h after the meal, followed by homeostasis during the extended fast. Essential and non-essential amino acids generally followed this same pattern, though some exhibited different trends after feeding: taurine, beta-alanine, and glycine (decreases or stability), alanine and glutamine (modest prolonged increases), and threonine, serine, asparagine, and valine (much larger short-term increases). Plasma non-esterified fatty acid concentrations declined markedly through 48h after the 2.6% meal. These data are interpreted in light of companion studies showing elevations in aerobic metabolic rate, urea production, rectal gland function, metabolic

  20. Identification of an Epoxide Metabolite of Lycopene in Human Plasma Using 13C-Labeling and QTOF-MS

    Directory of Open Access Journals (Sweden)

    Morgan J. Cichon

    2018-03-01

    Full Text Available The carotenoid lycopene is a bioactive component of tomatoes and is hypothesized to reduce risk of several chronic diseases, such as prostate cancer. The metabolism of lycopene is only beginning to be understood and some studies suggest that metabolites of lycopene may be partially responsible for bioactivity associated with the parent compound. The detection and characterization of these compounds in vivo is an important step in understanding lycopene bioactivity. The metabolism of lycopene likely involves both chemical and enzymatic oxidation. While numerous lycopene metabolites have been proposed, few have actually been identified in vivo following lycopene intake. Here, LC-QTOF-MS was used along with 13C-labeling to investigate the post-prandial oxidative metabolism of lycopene in human plasma. Previously reported aldehyde cleavage products were not detected, but a lycopene 1,2-epoxide was identified as a new candidate oxidative metabolite.

  1. Identification of an Epoxide Metabolite of Lycopene in Human Plasma Using 13C-Labeling and QTOF-MS.

    Science.gov (United States)

    Cichon, Morgan J; Moran, Nancy E; Riedl, Ken M; Schwartz, Steven J; Clinton, Steven K

    2018-03-20

    The carotenoid lycopene is a bioactive component of tomatoes and is hypothesized to reduce risk of several chronic diseases, such as prostate cancer. The metabolism of lycopene is only beginning to be understood and some studies suggest that metabolites of lycopene may be partially responsible for bioactivity associated with the parent compound. The detection and characterization of these compounds in vivo is an important step in understanding lycopene bioactivity. The metabolism of lycopene likely involves both chemical and enzymatic oxidation. While numerous lycopene metabolites have been proposed, few have actually been identified in vivo following lycopene intake. Here, LC-QTOF-MS was used along with 13 C-labeling to investigate the post-prandial oxidative metabolism of lycopene in human plasma. Previously reported aldehyde cleavage products were not detected, but a lycopene 1,2-epoxide was identified as a new candidate oxidative metabolite.

  2. SYSTEM OPTIMIZATION FOR THE AUTOMATIC SIMULTANEOUS DETERMINATION OF ARSENIC, SELENIUM, AND ANTIMONY, USING HYDRIDE GENERATION INTRODUCTION TO AN INDUCTIVELY COUPLED PLASMA.

    Science.gov (United States)

    Pyen, Grace S.; Browner, Richard F.; Long, Stephen

    1986-01-01

    A fixed-size simplex has been used to determine the optimum conditions for the simultaneous determination of arsenic, selenium, and antimony by hydride generation and inductively coupled plasma emission spectrometry. The variables selected for the simplex were carrier gas flow rate, rf power, viewing height, and reagent conditions. The detection limit for selenium was comparable to the preoptimized case, but there were twofold and fourfold improvements in the detection limits for arsenic and antimony, respectively. Precision of the technique was assessed with the use of artificially prepared water samples.

  3. Plasma Metabolites Predict Severity of Depression and Suicidal Ideation in Psychiatric Patients-A Multicenter Pilot Analysis.

    Science.gov (United States)

    Setoyama, Daiki; Kato, Takahiro A; Hashimoto, Ryota; Kunugi, Hiroshi; Hattori, Kotaro; Hayakawa, Kohei; Sato-Kasai, Mina; Shimokawa, Norihiro; Kaneko, Sachie; Yoshida, Sumiko; Goto, Yu-Ichi; Yasuda, Yuka; Yamamori, Hidenaga; Ohgidani, Masahiro; Sagata, Noriaki; Miura, Daisuke; Kang, Dongchon; Kanba, Shigenobu

    2016-01-01

    Evaluating the severity of depression (SOD), especially suicidal ideation (SI), is crucial in the treatment of not only patients with mood disorders but also psychiatric patients in general. SOD has been assessed on interviews such as the Hamilton Rating Scale for Depression (HAMD)-17, and/or self-administered questionnaires such as the Patient Health Questionnaire (PHQ)-9. However, these evaluation systems have relied on a person's subjective information, which sometimes lead to difficulties in clinical settings. To resolve this limitation, a more objective SOD evaluation system is needed. Herein, we collected clinical data including HAMD-17/PHQ-9 and blood plasma of psychiatric patients from three independent clinical centers. We performed metabolome analysis of blood plasma using liquid chromatography mass spectrometry (LC-MS), and 123 metabolites were detected. Interestingly, five plasma metabolites (3-hydroxybutyrate (3HB), betaine, citrate, creatinine, and gamma-aminobutyric acid (GABA)) are commonly associated with SOD in all three independent cohort sets regardless of the presence or absence of medication and diagnostic difference. In addition, we have shown several metabolites are independently associated with sub-symptoms of depression including SI. We successfully created a classification model to discriminate depressive patients with or without SI by machine learning technique. Finally, we produced a pilot algorithm to predict a grade of SI with citrate and kynurenine. The above metabolites may have strongly been associated with the underlying novel biological pathophysiology of SOD. We should explore the biological impact of these metabolites on depressive symptoms by utilizing a cross species study model with human and rodents. The present multicenter pilot study offers a potential utility for measuring blood metabolites as a novel objective tool for not only assessing SOD but also evaluating therapeutic efficacy in clinical practice. In addition

  4. Plasma Metabolites Predict Severity of Depression and Suicidal Ideation in Psychiatric Patients-A Multicenter Pilot Analysis.

    Directory of Open Access Journals (Sweden)

    Daiki Setoyama

    Full Text Available Evaluating the severity of depression (SOD, especially suicidal ideation (SI, is crucial in the treatment of not only patients with mood disorders but also psychiatric patients in general. SOD has been assessed on interviews such as the Hamilton Rating Scale for Depression (HAMD-17, and/or self-administered questionnaires such as the Patient Health Questionnaire (PHQ-9. However, these evaluation systems have relied on a person's subjective information, which sometimes lead to difficulties in clinical settings. To resolve this limitation, a more objective SOD evaluation system is needed. Herein, we collected clinical data including HAMD-17/PHQ-9 and blood plasma of psychiatric patients from three independent clinical centers. We performed metabolome analysis of blood plasma using liquid chromatography mass spectrometry (LC-MS, and 123 metabolites were detected. Interestingly, five plasma metabolites (3-hydroxybutyrate (3HB, betaine, citrate, creatinine, and gamma-aminobutyric acid (GABA are commonly associated with SOD in all three independent cohort sets regardless of the presence or absence of medication and diagnostic difference. In addition, we have shown several metabolites are independently associated with sub-symptoms of depression including SI. We successfully created a classification model to discriminate depressive patients with or without SI by machine learning technique. Finally, we produced a pilot algorithm to predict a grade of SI with citrate and kynurenine. The above metabolites may have strongly been associated with the underlying novel biological pathophysiology of SOD. We should explore the biological impact of these metabolites on depressive symptoms by utilizing a cross species study model with human and rodents. The present multicenter pilot study offers a potential utility for measuring blood metabolites as a novel objective tool for not only assessing SOD but also evaluating therapeutic efficacy in clinical practice. In

  5. Arsenic exposure from drinking water is associated with decreased gene expression and increased DNA methylation in peripheral blood

    Energy Technology Data Exchange (ETDEWEB)

    Ameer, Syeda Shegufta [Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund (Sweden); Engström, Karin [Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund (Sweden); Institute of Environmental Medicine, Unit of Metals & Health, Karolinska Institutet, Stockholm (Sweden); Hossain, Mohammad Bakhtiar [Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund (Sweden); Concha, Gabriela [Science Department, Risk Benefit Assessment Unit, National Food Agency, Uppsala (Sweden); Vahter, Marie [Institute of Environmental Medicine, Unit of Metals & Health, Karolinska Institutet, Stockholm (Sweden); Broberg, Karin, E-mail: Karin.broberg@ki.se [Institute of Environmental Medicine, Unit of Metals & Health, Karolinska Institutet, Stockholm (Sweden)

    2017-04-15

    Background: Exposure to inorganic arsenic increases the risk of cancer and non-malignant diseases. Inefficient arsenic metabolism is a marker for susceptibility to arsenic toxicity. Arsenic may alter gene expression, possibly by altering DNA methylation. Objectives: To elucidate the associations between arsenic exposure, gene expression, and DNA methylation in peripheral blood, and the modifying effects of arsenic metabolism. Methods: The study participants, women from the Andes, Argentina, were exposed to arsenic via drinking water. Arsenic exposure was assessed as the sum of arsenic metabolites in urine (U-As), using high performance liquid-chromatography hydride-generation inductively-coupled-plasma-mass-spectrometry, and arsenic metabolism efficiency was assessed by the urinary fractions (%) of the individual metabolites. Genome-wide gene expression (N = 80 women) and DNA methylation (N = 93; 80 overlapping with gene expression) in peripheral blood were measured using Illumina DirectHyb HumanHT-12 v4.0 and Infinium Human-Methylation 450K BeadChip, respectively. Results: U-As concentrations, ranging 10–1251 μg/L, was associated with decreased gene expression: 64% of the top 1000 differentially expressed genes were down-regulated with increasing U-As. U-As was also associated with hypermethylation: 87% of the top 1000 CpGs were hypermethylated with increasing U-As. The expression of six genes and six individual CpG sites were significantly associated with increased U-As concentration. Pathway analyses revealed enrichment of genes related to cell death and cancer. The pathways differed somewhat depending on arsenic metabolism efficiency. We found no overlap between arsenic-related gene expression and DNA methylation for individual genes. Conclusions: Increased arsenic exposure was associated with lower gene expression and hypermethylation in peripheral blood, but with no evident overlap. - Highlights: • Women exposed to inorganic arsenic were studied for

  6. Catalase Has a Key Role in Protecting Cells from the Genotoxic Effects of Monomethylarsonous Acid, a Highly Active Metabolite of Arsenic

    Science.gov (United States)

    ABSTRACT Although it is widely known that arsenic-contaminated drinking water causes many diseases, arsenic’s exact mode of action (MOA) is not fully understood. Induction of oxidative stress has been proposed as an important key event in the toxic MOA of arsenic. The author's...

  7. Measurement of caffeine and its three primary metabolites in human plasma by HPLC-ESI-MS/MS and clinical application.

    Science.gov (United States)

    Chen, Feng; Hu, Zhe-Yi; Parker, Robert B; Laizure, S Casey

    2017-06-01

    Caffeine is a mild stimulant with significant potential for abuse, being consumed in larger doses with the widespread availability of energy drinks and by novel routes of administration such as inspired powder, oral sprays and electronic cigarettes. How these recent changes in caffeine consumption affecting caffeine disposition and abuse potential is of growing concern. In the study of caffeine disposition in humans, it is common to only measure the caffeine concentration; however, caffeine's three major metabolites (paraxanthine, theobromine and theophylline) retain central nervous system stimulant activity that may contribute to the overall pharmacological activity and toxicity. Therefore, it would be scientifically more rigorous to measure caffeine and its major metabolites in the evaluation of caffeine disposition in human subjects. Herein, we report a method for the simultaneous quantification of caffeine and its three major metabolites in human plasma by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry (HPLC-ESI-MS/MS). Human plasma samples were treated by simple protein precipitation and the analytes were separated using a 6 min gradient program. Precision and accuracy were well within in the 15% acceptance range. The simple sample preparation, short runtime, sensitivity and the inclusion of caffeine's major metabolites make this assay methodology optimal for the study of caffeine's pharmacokinetics and pharmacodynamics in human subjects. Copyright © 2016 John Wiley & Sons, Ltd.

  8. Speciation of eight arsenic compounds in human urine by high performance liquid chromatography with inductively coupled plasma mass spectrometric detection using antimonate for internal chromatographic standardization

    DEFF Research Database (Denmark)

    Larsen, Erik Huusfeldt; Pritzl, G.; Hansen, S. H.

    1993-01-01

    Four anionic and four cationic arsenic compounds in urine were separated by anion- and cation-exchange high-performance liquid chromatography and detected by inductively coupled plasma mass spectrometry (ICP-MS) at m/z 75. The species were the anions arsenite, arsenate, monomethylarsonate...... and dimethylarsinate and the cations arsenobetaine, trimethylarsine oxide, arsenocholine and the tetramethylarsonium ion. Hexahydroxyantimonate(III) was co-chromatographed with the arsenic anions but detected at m/z 121 and used as an internal standard for their qualitative analysis. Arsenite was prone to oxidation....... The argon chloride interference at m/z 75 was eliminated by chromatographic separation of the chloride present in the sample from the arsenic analytes. The ClO+ ion detected at m/z 51 and 53 was used to monitor the retention time of chloride in the anion-exchange system. The chloride eluted about 100 s...

  9. [Simultaneous determination of 7 arsenic species in chicken muscle and chicken liver with high performance liquid chromatography-inductively coupled plasma mass spectrometry].

    Science.gov (United States)

    Yang, Lijun; Hu, Qiaoru; Guo, Wei; Liu, Yumin; Song, Xiaohua; Zhang, Pengcheng

    2011-05-01

    A method for the simultaneous determination of 7 arsenic species was developed with high performance liquid chromatography and inductively coupled plasma mass spectrometry (HPLC-ICP-MS). The sample was extracted with artificial gastric juice. The HPLC separation was performed on an anion analytical column utilizing a gradient elution program of ammonium carbonate and water as the mobile phase. Identification and quantification were achieved by ICP-MS. Good linearities of 7 arsenic species were observed in the range from 1 microg/kg to 50 microg/kg with the correlation coefficients greater than 0.999. The average recoveries of 7 arsenic species spiked at the three levels of 1, 2 and 10 microg/kg ranged from 84.3% to 106.6% with the relative standard deviations of 1.4%-4.2%. The quantification limits of 7 arsenic species were 1 microg/kg. The method was proved to be good reproducibility, high sensitivity and simple preprocessing. This method is suitable for the simultaneous determination of 7 arsenic species in chicken muscle and chicken liver.

  10. Simultaneous determination of arsenic and mercury species in rice by ion-pairing reversed phase chromatography with inductively coupled plasma mass spectrometry.

    Science.gov (United States)

    Fang, Yong; Pan, Yushi; Li, Peng; Xue, Mei; Pei, Fei; Yang, Wenjian; Ma, Ning; Hu, Qiuhui

    2016-12-15

    An analytical method using reversed phase chromatography-inductively coupled plasma mass spectrometry for arsenic and mercury speciation analysis was described. The effect of ion-pairing reagent on simultaneous separation of four arsenic (arsenite, arsenate, monomethlyarsonate and dimethylarsinate) and three mercury species (inorganic mercury (Hg(II)), methylmecury and ethylmercury) was investigated. Parameters including concentrations and pH of the mobile phase were optimized. The separation and re-equilibration time was attained within 20min. Meanwhile, a sequential extraction method for arsenic and mercury in rice was tested. Subsequently, 1% HNO3 microwave-assisted extraction was chosen. Calibration curves based on peak area measurements were linear with correlation coefficient greater than 0.9958 for each species in the range studied. The detection limits of the species were in the range of 0.84-2.41μg/L for arsenic and 0.01-0.04μg/L for mercury, respectively. The proposed method was then successfully applied for the simultaneous determination of arsenic and mercury species in rice flour standard material and two kinds of rice from local markets. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Time-series responses of swine plasma metabolites to ingestion of diets containing myo-inositol or phytase.

    Science.gov (United States)

    Cowieson, Aaron J; Roos, Franz F; Ruckebusch, Jean-Paul; Wilson, Jonathan W; Guggenbuhl, Patrick; Lu, Hang; Ajuwon, Kolapo M; Adeola, Olayiwola

    2017-12-01

    The effect of the ingestion of diets containing either myo-inositol or exogenous phytase on plasma metabolites was examined using 29 kg barrows. The diets were: control (maize, soya, rapeseed, rice bran), control plus 2 g/kg myo-inositol, control plus 1000 phytase units (FYT)/kg or 3000 FYT/kg exogenous phytase. Pigs were housed in a PigTurn device and blood was collected, from jugular catheters, via an automated system at -30, (30 min before feeding), 0, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300 and 360 min post-feeding. The addition of 2 g/kg myo-inositol to the basal diet resulted in an increase in plasma myo-inositol concentration that was evident 45-60 min after diet introduction and persisted to 360 min post-feeding. Similarly, supplementation of the basal diet with either 1000 or 3000 FYT/kg exogenous phytase resulted in an increase in plasma myo-inositol concentration that was still rising 360 min post-feeding. Plasma P concentration was increased over time by the addition of 1000 and 3000 FYT/kg phytase, but not by the addition of myo-inositol. Other plasma metabolites examined were not affected by dietary treatment. It can be concluded that oral delivery of myo-inositol results in rapid increase in plasma myo-inositol concentrations that peak approximately 45-60 min after feeding. Use of supplemental phytase achieves similar increases in myo-inositol concentration in plasma but the appearance is more gradual. Furthermore, supplementation of pig diets with exogenous phytase results in rapid appearance of P in plasma that may be sustained over time relative to diets with no added phytase.

  12. Monitoring nicotine intake from e-cigarettes: measurement of parent drug and metabolites in oral fluid and plasma.

    Science.gov (United States)

    Papaseit, Esther; Farré, Magí; Graziano, Silvia; Pacifici, Roberta; Pérez-Mañá, Clara; García-Algar, Oscar; Pichini, Simona

    2017-03-01

    Electronic cigarettes (e-cig) known as electronic nicotine devices recently gained popularity among smokers. Despite many studies investigating their safety and toxicity, few examined the delivery of e-cig-derived nicotine and its metabolites in alternative biological fluids. We performed a randomized, crossover, and controlled clinical trial in nine healthy smokers. Nicotine (NIC), cotinine (COT), and trans-3'-hydroxycotinine (3-HCOT) were measured in plasma and oral fluid by liquid chromatography-tandem mass spectrometry after consumption of two consecutive e-cig administrations or two consecutive tobacco cigarettes. NIC and its metabolites were detected both in oral fluid and plasma following both administration conditions. Concentrations in oral fluid resulted various orders of magnitude higher than those observed in plasma. Oral fluid concentration of tobacco cigarette and e-cig-derived NIC peaked at 15 min after each administration and ranged between 1.0 and 1396 μg/L and from 0.3 to 860 μg/L; those of COT between 52.8 and 110 μg/L and from 33.8 to 94.7 μg/L; and those of 3-HCOT between 12.4 and 23.5 μg/L and from 8.5 to 24.4 μg/L. The oral fluid to plasma concentration ratio of both e-cig- and tobacco cigarette-derived NIC peaked at 15 min after both administrations and correlated with oral fluid NIC concentration. The obtained results support the measurement of NIC and metabolites in oral fluid in the assessment of intake after e-cig use and appear to be a suitable alternative to plasma when monitoring nicotine delivery from e-cig for clinical and toxicological studies.

  13. PCB 28 metabolites elimination kinetics in human plasma on a real case scenario: Study of hydroxylated polychlorinated biphenyl (OH-PCB) metabolites of PCB 28 in a highly exposed German Cohort.

    Science.gov (United States)

    Quinete, Natalia; Esser, André; Kraus, Thomas; Schettgen, Thomas

    2017-07-05

    Polychlorinated biphenyls (PCBs) are suspected of carcinogenic, neurotoxic and immunotoxic effects in animals and humans. Although background levels of PCBs have been slowly decreased after their ban, they are still among the most persistent and ubiquitous pollutants in the environment, remaining the subject of great concern. PCB 28 is a trichlorinated PCB found in high concentrations not only in human plasma but also in indoor air in Europe, yet little is known about its metabolic pathway and potential metabolites in humans. The present study aims to elucidate the kinetics of metabolite formation and elimination by analyzing four hydroxylated PCBs (OH-PCBs) in human plasma as potential metabolites of the PCB 28 congener. For this purpose, the study was conducted in plasma samples of highly PCB-exposed individuals (N=268), collected from 2010 to 2014 as a representation of a real case scenario with longitudinal data. OH-PCBs have been predicted, synthesized in the course of this study and further identified and quantitated in human plasma. This is the first time that previously unknown PCB 28 metabolites have been measured in human plasma and half-lives have been estimated for PCB metabolites, which could then provide further understanding in the toxicological consequences of exposure to PCBs in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Effects of feeding metabolite combinations from lactobacillus plantarum on plasma and breast meat lipids in Broiler Chickens

    Directory of Open Access Journals (Sweden)

    TC Loh

    2013-12-01

    Full Text Available The effects of feeding different doses of metabolite combination of L. plantarum RS5, RI11, RG14 and RG11 strains (Com3456 on cholesterol reduction in plasma and breast meat in broiler chickens and the possible mechanism was studied. A total of 504 male Ross broilers were grouped into 7 treatments and offered with different diets: (i standard corn-soybean based diet (-ve control; (ii standard cornsoybean based diet + neomycin and oxytetracycline (+ve control; (iii standard corn-soybean based diet + 0.1% metabolite combination of L. plantarum RS5, RI11, RG14 and RG11 strains (Com3456; (iv standard corn-soybean based diet + 0.2% of Com3456; (v standard cornsoybean based diet + 0.3% of Com3456 (vi standard corn-soybean based diet + 0.4% of Com3456 and (vii standard corn-soybean based diet + 0.5% of Com3456. The metabolite combinations supplemented in the diet of broilers reduced protein, cholesterol esters concentration in very low-density lipoprotein particles. The present of organic acids and proteinaceous compound in the metabolite combinations as found in previous study also increased lactic acid bacteria count in small intestine digesta and improved bile salts deconjugation ability of lactic acid bacteria.

  15. [Determination of lidocaine and its metabolites in human plasma by liquid chromatography in combination with tandem mass spectrometry].

    Science.gov (United States)

    Xiang, Jin; Zhang, Cheng; Yu, Qin; Liang, Mao-Zhi; Qin, Yong-Ping; Nan, Feng

    2010-07-01

    To establish a liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for the determination of lidocaine (LDC) and its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), in human plasma. METHODS; The assay was conducted with an API 3000 HPLC-MS/MS system consisted of a Ultimate C18 column (50 x 4.6 mm, 5 microm). The mobile phase consisted of methanol: 5 mmol/ L ammonium acetate (50:50, pH was adjusted to 5.0 by formic acid) and the flow rate was set at 0.2 mL/min. The alkalinized sample was extracted with ethyl acetate. After evaporation of the organic layer, the residue was dissolved in mobile phase and the drug was determined by HPLC-MS/MS using electrospray ionization. The calibration curve was linear in a range from 15.625 to 2000 ng/mL for LDC. Linear calibration curves were obtained in the range of 1.5625 to 200 ng/mL for both for MEGX and GX. The limit of quantification for LDC, MEGX and GX was set at 15.625, 1.5625 and 1.5625 ng/mL. This method for the quantitative determination of lidocaine and its metabolites in human plasma is simple, rapid, sensitive and accurate. Therefore it can be used for the determination of lidocaine and its metabolites in clinical practice.

  16. Simultaneous quantification of caffeine and its three primary metabolites in rat plasma by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Choi, Eu Jin; Bae, Soo Hyeon; Park, Jung Bae; Kwon, Min Jo; Jang, Su Min; Zheng, Yu Fen; Lee, Young Sun; Lee, Su-Jun; Bae, Soo Kyung

    2013-12-01

    A rapid, sensitive, simple and accurate LC-MS/MS method for the simultaneous quantitation of caffeine, and its three primary metabolites, theobromine, paraxanthine, and theophylline, in rat plasma was developed and validated. Chromatographic separation was performed on an Agilent Poroshell 120 EC-C18 column using 1 μg/mL acetaminophen as an internal standard. Each sample was run at 0.5 mL/min for a total run time of 7 min/sample. Detection and quantification were performed using a mass spectrometer in selected reaction-monitoring mode with positive electrospray ionization. The lower limit of quantification was 5 ng/mL for all analytes with linear ranges up to 5000 ng/mL for caffeine and 1000 ng/mL for its metabolites. The coefficient of variation for assay precision was less than 12.6%, with an accuracy of 93.5-114%. The assay was successfully applied to determine plasma concentrations of caffeine, theobromine, paraxanthine, and theophylline in rat administered various energy drinks containing the same caffeine content. Various energy drinks exhibited considerable variability in the pharmacokinetic profiles of caffeine and its three primary metabolites, even containing the same caffeine. Different additives of energy drinks might contribute to these results. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Arsenic, cadmium and lead concentrations in Yerba mate commercialized in Southern Brazil by inductively coupled plasma mass spectrometry

    Directory of Open Access Journals (Sweden)

    Lisia Maria Gobbo dos Santos

    2017-12-01

    Full Text Available ABSTRACT: “Mate” or “Yerba Mate” (Ilex paraguariensis is a native South American plant, commonly consumed in Argentina, Paraguay, Uruguay and southern Brazil. Recent research has detected the presence of many vitamins and metals in this plant. Theses metals are also part of yerba mate’s mineral composition, due to soil and water contamination by pesticides and fertilizers, coal and oil combustion, vehicle emissions, mining, smelting, refining and the incineration of urban and industrial waste. Regardless of their origin, some inorganic elements, such as arsenic, cadmium and lead, are considered toxic, since they accumulate in all plant tissues and are, thus, introduced into the food chain. In this context, the aim of the present study was to determine and compare arsenic, cadmium, lead concentrations in 104 samples of yerba mate (Ilex paraguariensis marketed, and consumed in three southern Brazilian States, namely Paraná (PR, Santa Catarina (SC and Rio Grande do Sul (RS. Each element was determined by inductively coupled plasma mass spectrometry (ICP-MS, on a Nexion 300D equipment (Perkin Elmer. As, Cd and Pb concentrations in yerba mate leaves ranged from 0.015 to 0.15mg kg-1, 0.18 to 1.25mg kg-1 and 0.1 to 1.20mg kg-1, respectively. Regarding Cd, 84% of the samples from RS, 63% from PR and 75% from SC showed higher concentrations than the maximum permissible limit of 0.4mg kg-1 established by the Brazilian National Sanitary Surveillance Agency (ANVISA, while 7% of the samples from RS and 5% from PR were unsatisfactory for Pb. Concentrations were below the established ANVISA limit of 0.6mg kg-1 for all samples.

  18. Elevated prostaglandin E metabolites and abnormal plasma fatty acids at baseline in pediatric cystic fibrosis patients: a pilot study.

    Science.gov (United States)

    O'Connor, Michael Glenn; Thomsen, Kelly; Brown, Rebekah F; Laposata, Michael; Seegmiller, Adam

    2016-10-01

    Airway inflammation is a significant contributor to the morbidity of cystic fibrosis (CF) disease. One feature of this inflammation is the production of oxygenated metabolites, such as prostaglandins. Individuals with CF are known to have abnormal metabolism of fatty acids, typically resulting in reduced levels of linoleic acid (LA) and docosahexaenoic acid (DHA). This is a randomized, double-blind, cross-over clinical trial of DHA supplementation with endpoints of plasma fatty acid levels and prostaglandin E metabolite (PGE-M) levels. Patients with CF age 6-18 years with pancreatic insufficiency were recruited. Each participant completed 3 four-week study periods: DHA at two different doses (high dose and low dose) and placebo with a minimum 4 week wash-out between each period. Blood, urine, and exhaled breath condensate (EBC) were collected at baseline and after each study period for measurement of plasma fatty acids as well as prostaglandin E metabolites. Seventeen participants were enrolled, and 12 participants completed all 3 study periods. Overall, DHA supplementation was well tolerated without significant adverse events. There was a significant increase in plasma DHA levels with supplementation, but no significant change in arachidonic acid (AA) or LA levels. However, at baseline, AA levels were lower and LA levels were higher than previously reported for individuals with CF. Urine PGE-M levels were elevated in the majority of participants at baseline, and while levels decreased with DHA supplementation, they also decreased with placebo. Urine PGE-M levels are elevated at baseline in this cohort of pediatric CF patients, but there was no significant change in these levels with DHA supplementation compared to placebo. In addition, baseline plasma fatty acid levels for this cohort showed some difference to prior reports, including higher levels of LA and lower levels of AA, which may reflect changes in clinical care, and consequently warrants further

  19. Increased plasma concentrations of vitamin D metabolites and vitamin D binding protein in women using hormonal contraceptives: a cross-sectional study

    DEFF Research Database (Denmark)

    Liendgaard, Ulla Kristine Møller; við Streym, Susanna; Jensen, Lars Thorbjørn

    2013-01-01

    UNLABELLED: Use of hormonal contraceptives (HC) may influence total plasma concentrations of vitamin D metabolites. A likely cause is an increased synthesis of vitamin D binding protein (VDBP). Discrepant results are reported on whether the use of HC affects free concentrations of vitamin D...... metabolites. AIM: In a cross-sectional study, plasma concentrations of vitamin D metabolites, VDBP, and the calculated free vitamin D index in users and non-users of HC were compared and markers of calcium and bone metabolism investigated. RESULTS: 75 Caucasian women aged 25-35 years were included during......, parathyroid hormone, and calcitonin, p > 0.21) or bone metabolism (plasma bone specific alkaline phosphatase, osteocalcin, and urinary NTX/creatinine ratio) between groups. IN CONCLUSION: Use of HC is associated with 13%-25% higher concentrations of total vitamin D metabolites and VDBP. This however...

  20. Influence of weaning regimen on intake, growth characteristics and plasma blood metabolites in male buffalo calves.

    Science.gov (United States)

    Rashid, M A; Pasha, T N; Jabbar, M A; Ijaz, A; Rehman, H; Yousaf, M S

    2013-09-01

    Experiment was conducted to evaluate the effect of weaning age on growth performance, feed intake, feed efficiency (FE) and blood metabolites in Nili-Ravi male buffalo (Bubalus bubalis) calves. Twenty-four male buffalo calves were assigned to one of the three treatment groups: continuous milk feeding (CMF), limited milk feeding (LMF) and early weaning (EW), and weaned off milk at 12, 10 and 8 weeks of age, respectively. For the first 3 days after birth, calves in all three treatments were fed colostrum, and were then moved to individual milk feeding at 10% of BW for the next 6 weeks. Thereafter, the provision of milk to the CMF group was gradually tapered to zero through week 12, using week 6 intakes as a base. The LMF calves were fed milk at 7.5%, 5.0%, 3.5%, and 1.5% of BW during weeks 7 to 10, respectively. Lastly, calves in the EW group were fed milk at 5.0% and 2.5% of BW at weeks 7 and 8, respectively. Calf starter (CS) feed was also provided ad libitum from weeks 2 to 12 and individual intakes were recorded on a daily basis. Blood samples were taken from weeks 6 to 12, on a weekly basis; whereas, the BW, heart girth, withers height and hip width were measured at the start of experiment and later on a weekly basis. Weight gain, average daily gain, and body measurements were the same across all three groups. Milk intake was lower (P intake was greater (P calves compared with the other treatment groups. Dry matter intake was greater (P calves compared with the CMF calves. The FE was greater (P calves compared with the LMF and EW treatment groups. Blood glucose concentration was similar among the treatments; however, blood urea nitrogen was greater (P calves compared with the CMF and LMF groups. Plasma concentration of non-esterified fatty acids was higher (P calves compared with the CMF calves. In light of these results, it is evident that buffalo calves can be successfully weaned as early as 8 weeks of age without negatively affecting their growth performance.

  1. The course of some bone remodelling plasma metabolites in healthy horses and in horses offered a calcium-deficient diet.

    Science.gov (United States)

    de Behr, V; Daron, D; Gabriel, A; Remy, B; Dufrasne, I; Serteyn, D; Istasse, L

    2003-04-01

    An inquiry was carried out to assess the concentrations of plasma metabolites related to bone remodelling in 21 saddle horses of Warmblood breed aged 4-26 years, five draught horses of Ardennes breed aged 4-10 years, and 10 Ardennes foals aged 9-11 months. They were fed according to normal feeding practice in Belgium. The changes in some bone remodelling plasma metabolite concentrations were studied when an unbalanced diet was offered and later corrected for four Warmblood horses. Bone formation was evaluated by bone alkaline phosphatase (BALP), total alkaline phosphatase (TALP) and osteocalcin (bone gla-protein, OC). Bone resorption was assessed by hydroxyproline (HYP). Total calcium, ionized calcium, phosphorus (P) and 25-hydroxyvitamin D3 [25-(OH)D] concentrations were more or less constant. The comparison of four bone remodelling factors between the Ardennes and Warmblood horses showed higher concentrations in the Ardennes breed. Bone marker concentrations decreased according to age. The correction of the unbalanced Ca : P diet induced inconsistent effects at plasma level. The interpretation of the different bone parameters appeared to be difficult if not associated with other parameters such as a complete anamnesis and clinical examination of the animal in addition to dietary evaluation.

  2. Urinary arsenic concentrations and speciation in residents living in an area with naturally contaminated soils

    Energy Technology Data Exchange (ETDEWEB)

    Fillol, Clemence, E-mail: c.fillol@invs.sante.fr [Universite Paris Descartes, Laboratoire Sante Publique et Environnement - EA 4064, Paris (France); Institut de veille sanitaire, Departement Sante environnement, Saint-Maurice (France); Dor, Frederic [Institut de veille sanitaire, Departement Sante environnement, Saint-Maurice (France); Labat, Laurence [CHRU de Lille, Laboratoire de Toxicologie et Genopathies, Lille (France); Boltz, Patricia [Centre antipoison et de toxicovigilance de Nancy (France); Le Bouard, Jerome [Direction Regionale des Affaires Sanitaires et Sociales, Meurthe-et-Moselle (France); Mantey, Karine [Cellule Interregionale d' epidemiologie de l' Est (France); Mannschott, Christian [Direction Departementale des Affaires Sanitaires et Sociales 54, Meurthe-et-Moselle (France); Puskarczyk, Emmanuel [Centre antipoison et de toxicovigilance de Nancy (France); Viller, Frederique [Cellule Interregionale d' epidemiologie de l' Est (France); Momas, Isabelle [Universite Paris Descartes, Laboratoire Sante Publique et Environnement - EA 4064, Paris (France); Seta, Nathalie [Universite Paris Descartes, Laboratoire Sante Publique et Environnement - EA 4064, Paris (France); AP-HP, Hopital Bichat, Biochimie, Paris (France)

    2010-02-01

    A cross sectional study was carried out to evaluate arsenic exposure of residents living in an area with a soil naturally rich in arsenic (As), through urinary measurements. During the summer of 2007, 322 people aged over 7 years and resident in the study area for at least 4 days prior to the investigation were recruited. The sum of urinary inorganic arsenic and metabolites (iAs + MMA + DMA) and speciation were determined by graphite furnace atomic absorption spectrometry and high performance liquid chromatography coupled to inductively coupled plasma mass spectrometry, respectively. Geometric means levels of iAs + MMA + DMA were 3.6 {mu}g/L or 4.4 {mu}g/g creatinine. The percent of DMA, As(III) and MMA contribution to urinary arsenic concentrations was respectively 84.2%, 12% and 3.7%. We found significant associations between urinary arsenic concentrations and the consumption of seafood (p = 0.03), the consumption of wine (p = 0.03) and beer (p = 0.001), respectively 3 and 4 days before the investigation. When we focus on the various species, As(V) was rarely detected and DMA is the predominant metabolite composing the majority of measurable inorganic-related As in the urine. Considering the percent of DMA contribution to iAs + MMA + DMA urinary concentrations, almost half of the subjects had 100% of DMA contribution whatever the concentration of urinary As whereas the others had a lower DMA contribution, between 39 and 90%. Arsenic levels reported in this original study in France were between 2 and 4 times lower than in other studies dealing with iAs + MMA + DMA levels associated with soil arsenic exposure. Arsenic levels were similar to those observed in unexposed individuals in European countries, although 10% were above the French guideline values for the general population.

  3. Urinary arsenic concentrations and speciation in residents living in an area with naturally contaminated soils

    International Nuclear Information System (INIS)

    Fillol, Clemence; Dor, Frederic; Labat, Laurence; Boltz, Patricia; Le Bouard, Jerome; Mantey, Karine; Mannschott, Christian; Puskarczyk, Emmanuel; Viller, Frederique; Momas, Isabelle; Seta, Nathalie

    2010-01-01

    A cross sectional study was carried out to evaluate arsenic exposure of residents living in an area with a soil naturally rich in arsenic (As), through urinary measurements. During the summer of 2007, 322 people aged over 7 years and resident in the study area for at least 4 days prior to the investigation were recruited. The sum of urinary inorganic arsenic and metabolites (iAs + MMA + DMA) and speciation were determined by graphite furnace atomic absorption spectrometry and high performance liquid chromatography coupled to inductively coupled plasma mass spectrometry, respectively. Geometric means levels of iAs + MMA + DMA were 3.6 μg/L or 4.4 μg/g creatinine. The percent of DMA, As(III) and MMA contribution to urinary arsenic concentrations was respectively 84.2%, 12% and 3.7%. We found significant associations between urinary arsenic concentrations and the consumption of seafood (p = 0.03), the consumption of wine (p = 0.03) and beer (p = 0.001), respectively 3 and 4 days before the investigation. When we focus on the various species, As(V) was rarely detected and DMA is the predominant metabolite composing the majority of measurable inorganic-related As in the urine. Considering the percent of DMA contribution to iAs + MMA + DMA urinary concentrations, almost half of the subjects had 100% of DMA contribution whatever the concentration of urinary As whereas the others had a lower DMA contribution, between 39 and 90%. Arsenic levels reported in this original study in France were between 2 and 4 times lower than in other studies dealing with iAs + MMA + DMA levels associated with soil arsenic exposure. Arsenic levels were similar to those observed in unexposed individuals in European countries, although 10% were above the French guideline values for the general population.

  4. Screening Samples for Arsenic by Inductively Coupled Plasma-Mass Spectrometry for Treaty Samples

    Science.gov (United States)

    2014-02-01

    quality system in accordance with International Organization for Standardization/International Electrotechnical Commission ( ISO / IEC ) 17025 :2005...plasma-mass spectrometry ISO / IEC International Organization for Standardization/International Electrotechnical Commission L lewisite MDL method

  5. Whey protein delays gastric emptying and suppresses plasma fatty acids and their metabolites compared to casein, gluten, and fish protein

    DEFF Research Database (Denmark)

    Stanstrup, Jan; Schou, Simon S; Holmer-Jensen, Jens

    2014-01-01

    ), and cod (COD). Obese, nondiabetic subjects were included in the randomized, blinded, crossover meal study. Subjects ingested a high fat meal containing one of the four protein sources. Plasma samples were collected at five time points and metabolites analyzed using LC-Q-TOF-MS. In contrast to previous...... studies, the WI meal caused a decreased rate of gastric emptying compared to the other test meals. The WI meal also caused elevated levels of a number of amino acids, possibly stimulating insulin release leading to reduced plasma glucose. The WI meal also caused decreased levels of a number of fatty acids......, while the GLU meal caused elevated levels of a number of unidentified hydroxy fatty acids and dicarboxylic fatty acids. Also reported are a number of markers of fish intake unique to the COD meal....

  6. Total Arsenic Determination and Speciation in Infant Food Products by Ion Chromatography Inductively Coupled Plasma Mass Spectrometry

    Science.gov (United States)

    Health risk associated with dietary arsenic intake may be different for infants and adults. Seafood is the main contributor to arsenic intake for adults while terrestrial-based food is the primary source for infants. Processed infant food products such as rice-based cereals, mi...

  7. Effect of the long-term regular intake of virgin olive oil on the phenolic metabolites in human fasting plasma.

    Science.gov (United States)

    Valls, Rosa-Maria; Soler, Aranzazu; Girona, Josefa; Heras, Mercedes; Romero, Maria-Paz; Covas, Maria-Isabel; Solà, Rosa; Masana, Lluis; Motilva, Maria-Jose

    2010-09-21

    The effect of repeated consumption of virgin olive oil on endogenous phenolic metabolites of fasting plasma is unknown. For this reason, we hypothesized that regular long-term virgin olive oil intake could have an indirect protection effect on the endogenous phenols. Thus, the aim of the study was to determine the phenolic profile of human plasma in a fasting state of long-term regular virgin olive oil consumers, using the fasting plasma of non-consumers as a natural control. Forty participants living in the area of Reus (Catalonia, Spain) were selected, 20 life-long regular consumers of virgin olive oil and a natural control of 20 non-consumers, the latter being Rumanians who dislike the taste of olive oil. The diet was obtained from 3-day food records. The results showed similar phenolic composition of fasting plasmas of the two volunteer groups. Of special interest is that more of the compounds quantified showed higher concentration in fasting plasma from habitual virgin olive oil consumers. The compounds were semi-quantified using caffeic acid as the calibration standard. The quantification of fasting consumer's plasma showed higher concentration of a hydroxyflavanone type compound (2.90+/-0.04 microM vs 1.5+/-0.04 microM) and a catecholamine derivative (0.70+/-0.03 microM vs 0.56+/-0.03 microM) than the plasma of non-consumers (P<0.05). The results suggest an indirect protective mechanism of long-term regular virgin olive oil consumption related to the protection of the endogenous antioxidant system. Copyright 2010 Elsevier B.V. All rights reserved.

  8. Analysis of human plasma metabolites across different liquid chromatography/mass spectrometry platforms: Cross-platform transferable chemical signatures.

    Science.gov (United States)

    Telu, Kelly H; Yan, Xinjian; Wallace, William E; Stein, Stephen E; Simón-Manso, Yamil

    2016-03-15

    The metabolite profiling of a NIST plasma Standard Reference Material (SRM 1950) on different liquid chromatography/mass spectrometry (LC/MS) platforms showed significant differences. Although these findings suggest caution when interpreting metabolomics results, the degree of overlap of both profiles allowed us to use tandem mass spectral libraries of recurrent spectra to evaluate to what extent these results are transferable across platforms and to develop cross-platform chemical signatures. Non-targeted global metabolite profiles of SRM 1950 were obtained on different LC/MS platforms using reversed-phase chromatography and different chromatographic scales (conventional HPLC, UHPLC and nanoLC). The data processing and the metabolite differential analysis were carried out using publically available (XCMS), proprietary (Mass Profiler Professional) and in-house software (NIST pipeline). Repeatability and intermediate precision showed that the non-targeted SRM 1950 profiling was highly reproducible when working on the same platform (relative standard deviation (RSD) HPLC, UHPLC and nanoLC) on the same platform. A substantial degree of overlap (common molecular features) was also found. A procedure to generate consistent chemical signatures using tandem mass spectral libraries of recurrent spectra is proposed. Different platforms rendered significantly different metabolite profiles, but the results were highly reproducible when working within one platform. Tandem mass spectral libraries of recurrent spectra are proposed to evaluate the degree of transferability of chemical signatures generated on different platforms. Chemical signatures based on our procedure are most likely cross-platform transferable. Published in 2016. This article is a U.S. Government work and is in the public domain in the USA.

  9. Simultaneous analysis of regorafenib and sorafenib and three of their metabolites in human plasma using LC-MS/MS.

    Science.gov (United States)

    Allard, Marie; Khoudour, Nihel; Rousseau, Benoît; Joly, Charlotte; Costentin, Charlotte; Blanchet, Benoît; Tournigand, Christophe; Hulin, Anne

    2017-08-05

    A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, performed by electrospray ionization in positive mode using a triple quadrupole mass spectrometry, has been developed and validated for the simultaneous determination of regorafenib (REGO), its two metabolites regorafenib-M2 and regorafenib-M5, sorafenib (SORA), and its N-oxide metabolite in human plasma. Separation is achieved on an Hypersil Gold ® column using a gradient elution of 10mM ammonium formate containing 0.1% formic acid (A) and acetonitrile containing 0.1% formic acid (B) at a flow rate of 0.3mL/min. After addition of two internal standards and a protein precipitation, the supernatant is diluted two-fold in a 0.1% (v/v) formic acid solution. Two selected reaction monitoring transitions are used, for each analyte, one for quantitation and the second one for confirmation. The standard curves are ranged from 50 to 5 000ng/mL for REGO and its metabolites and 80 to 5 000ng/mL for SORA and its metabolite and were fitted to a 1/x weighted linear regression model. The method also showed satisfactory results in terms of sensitivity, specificity, precision (intra- and inter-day CV from 2.4 to 10.2%), accuracy (from 91.0 to 111.7%), recovery as well as stability of the analytes under various conditions. The method is usually used in clinical practice in order to improve the SORA treatment for renal carcinoma, REGO treatment for colorectal cancer and both for hepatocellular carcinoma. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Fat oxidation, hormonal and plasma metabolite kinetics during a submaximal incremental test in lean and obese adults.

    Science.gov (United States)

    Lanzi, Stefano; Codecasa, Franco; Cornacchia, Mauro; Maestrini, Sabrina; Salvadori, Alberto; Brunani, Amelia; Malatesta, Davide

    2014-01-01

    This study aimed to compare fat oxidation, hormonal and plasma metabolite kinetics during exercise in lean (L) and obese (O) men. Sixteen L and 16 O men [Body Mass Index (BMI): 22.9 ± 0.3 and 39.0 ± 1.4 kg · m(-2)] performed a submaximal incremental test (Incr) on a cycle-ergometer. Fat oxidation rates (FORs) were determined using indirect calorimetry. A sinusoidal model, including 3 independent variables (dilatation, symmetry, translation), was used to describe fat oxidation kinetics and determine the intensity (Fat(max)) eliciting maximal fat oxidation. Blood samples were drawn for the hormonal and plasma metabolite determination at each step of Incr. FORs (mg · FFM(-1) · min(-1)) were significantly higher from 20 to 30% of peak oxygen uptake (VO2peak) in O than in L and from 65 to 85% VO2peak in L than in O (p ≤ 0.05). FORs were similar in O and in L from 35 to 60% VO2peak. Fat max was 17% significantly lower in O than in L (poxidation kinetics were characterized by similar translation, significantly lower dilatation and left-shift symmetry in O compared with L (poxidation at high exercise intensities suggest that the difference in the fat oxidation kinetics is likely linked to impaired muscular capacity to oxidize NEFA in O. These results may have important implications for the appropriate exercise intensity prescription in training programs designed to optimize fat oxidation in O.

  11. Increased plasma concentrations of vasopressin, oxytocin, cortisol and the prostaglandin F2alpha metabolite during labour in the dog.

    Science.gov (United States)

    Olsson, K; Bergström, A; Kindahl, H; Lagerstedt, A-S

    2003-11-01

    This study investigated if the plasma vasopressin concentration increases during labour in the dog and whether the change in vasopressin correlates with that of oxytocin, 15-ketodihydro-PGF2alpha and cortisol. Five beagle dogs each delivered three to seven puppies. Blood samples were taken from a catheter inserted into the cephalic vein during labour and by venepuncture during the other periods. Vasopressin concentration increased from 2 +/- 0 pmol L-1 (anoestrus) to 26 +/- 11 pmol L-1 at the birth of the first puppy, remained high at the birth of the second puppy and then decreased. Oxytocin increased from 63 +/- 5 pmol L-1 (anoestrus) to 166 +/- 19 pmol L-1 at the birth of the first puppy and remained elevated throughout labour. The PGF2alpha metabolite concentration increased from 0.2 +/- 0.0 nmol L-1 (anoestrus) to 66 +/- 17 nmol L-1 at the birth of the first puppy and remained elevated 1 h after the completion of parturition. The cortisol concentration increased from 49 +/- 9 nmol L-1 (anoestrus) to 242 +/- 35 nmol L-1 at the birth of the first puppy, remained high during the birth of the second puppy and then declined. The plasma level of vasopressin was strongly correlated with that of cortisol but less with that of the PGF2alpha metabolite, and not significantly with the concentration of oxytocin. This indicates that the four hormones play different roles during labour in the dog.

  12. Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling

    Directory of Open Access Journals (Sweden)

    W. B. Mattes

    2013-01-01

    Full Text Available Addressing safety concerns such as drug-induced kidney injury (DIKI early in the drug pharmaceutical development process ensures both patient safety and efficient clinical development. We describe a unique adjunct to standard safety assessment wherein the metabolite profile of treated animals is compared with the MetaMap Tox metabolomics database in order to predict the potential for a wide variety of adverse events, including DIKI. To examine this approach, a study of five compounds (phenytoin, cyclosporin A, doxorubicin, captopril, and lisinopril was initiated by the Technology Evaluation Consortium under the auspices of the Drug Safety Executive Council (DSEC. The metabolite profiles for rats treated with these compounds matched established reference patterns in the MetaMap Tox metabolomics database indicative of each compound’s well-described clinical toxicities. For example, the DIKI associated with cyclosporine A and doxorubicin was correctly predicted by metabolite profiling, while no evidence for DIKI was found for phenytoin, consistent with its clinical picture. In some cases the clinical toxicity (hepatotoxicity, not generally seen in animal studies, was detected with MetaMap Tox. Thus metabolite profiling coupled with the MetaMap Tox metabolomics database offers a unique and powerful approach for augmenting safety assessment and avoiding clinical adverse events such as DIKI.

  13. Combined high-pressure liquid chromatography and radioimmunoassay method for the quantitation of Δ9-tetrahydrocannabinol and some of its metabolites in human plasma

    International Nuclear Information System (INIS)

    Williams, P.L.; Moffat, A.C.; King, L.J.

    1978-01-01

    A high-pressure liquid chromatography-radioimmunoassay (HPLC-RIA) method for the measurement of cannabinoid levels in plasma is described. The method is capable of quantifying 0.1 ng of a cannabinoid in 1 ml of plasma. The experimental procedure consists of an initial separation of cannabinoids in a plasma extract by HPLC followed by collection of the HPLC eluate and RIA. A chromatogram consisting of the cross-reacting cannabinoids in plasma may then be constructed. The plasma concentrations of cannabinoids with retention volumes equivalent to those of Δ 9 -terahydrocannabinol, cannabinol and mono-hydroxylated metabolites have been measured by this technique. (Auth.)

  14. Simultaneous determination of imperatorin and its 2 metabolites in dog plasma by using liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Wang, Lu; Lu, Wen; Shen, Qi; Wang, Shengjia; Zhou, Hui; Yu, Lushan; Wang, Sicen; Jiang, Huidi; He, Langchong; Zeng, Su

    2012-11-01

    In this study, 2 metabolites of imperatorin, imperatorin hydroxylate (IMH) and imperatorin epoxide (IME), were identified for the first time in dog plasma. A sensitive, specific, and accurate high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was then developed for the simultaneous quantification of imperatorin and its 2 metabolites in dog plasma. Separation was achieved on an Agilent ZORBAX Extend-C(18) column (2.1 mm × 50 mm, 3.5 μm) at 30 °C. The mobile phase consisted of 0.02% ammonium acetate solution-methanol with a gradient program at a flow rate of 0.3 mL/min. Detection was performed using an electrospray ionization source operating in positive ion multiple reaction monitoring mode and by monitoring the ion transitions from 271 to 203 m/z for imperatorin, 309.4-224.1 m/z for IMH, 287-203 m/z for IME, and 441.3-325.2 m/z for simvastatin (the internal standard). Good linearity was shown over the concentration range of 1-500 ng/mL for imperatorin, and 0.2-500 ng/mL for IMH and IME. The validated method was successfully applied to a pharmacokinetic study of imperatorin in beagle dogs. The pharmacokinetic profiles of imperatorin and its 2 metabolites showed sex differences after the i.v. administration of imperatorin at a dose of 5 mg/kg. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. ULTRASONIC NEBULIZATION AND ARSENIC VALENCE STATE CONSIDERATIONS PRIOR TO DETERMINATION VIA INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

    Science.gov (United States)

    An ultrasonic nebulizer (USN) was utilized as a sample introduction device for an inductively coupled plasma mass spectrometer in an attempt to increase the sensitivity for As. The USN produced a valence state response difference for As. The As response was suppressed approximate...

  16. A review on environmental factors regulating arsenic methylation in humans

    International Nuclear Information System (INIS)

    Tseng, C.-H.

    2009-01-01

    Subjects exposed to arsenic show significant inter-individual variation in urinary patterns of arsenic metabolites but insignificant day-to-day intra-individual variation. The inter-individual variation in arsenic methylation can be partly responsible for the variation in susceptibility to arsenic toxicity. Wide inter-ethnic variation and family correlation in urinary arsenic profile suggest a genetic effect on arsenic metabolism. In this paper the environmental factors affecting arsenic metabolism are reviewed. Methylation capacity might reduce with increasing dosage of arsenic exposure. Furthermore, women, especially at pregnancy, have better methylation capacity than their men counterparts, probably due to the effect of estrogen. Children might have better methylation capacity than adults and age shows inconsistent relevance in adults. Smoking and alcohol consumption might be associated with a poorer methylation capacity. Nutritional status is important in the methylation capacity and folate may facilitate the methylation and excretion of arsenic. Besides, general health conditions and medications might influence the arsenic methylation capacity; and technical problems can cause biased estimates. The consumption of seafood, seaweed, rice and other food with high arsenic contents and the extent of cooking and arsenic-containing water used in food preparation may also interfere with the presentation of the urinary arsenic profile. Future studies are necessary to clarify the effects of the various arsenic metabolites including the trivalent methylated forms on the development of arsenic-induced human diseases with the consideration of the effects of confounding factors and the interactions with other effect modifiers

  17. Coumestrol and its metabolite in mares' plasma after ingestion of phytoestrogen-rich plants: potent endocrine disruptors inducing infertility.

    Science.gov (United States)

    Ferreira-Dias, G; Botelho, M; Zagrajczuk, A; Rebordão, M R; Galvão, A M; Bravo, P Pinto; Piotrowska-Tomala, K; Szóstek, A Z; Wiczkowski, W; Piskula, M; Fradinho, M J; Skarzynski, D J

    2013-10-01

    Phytoestrogens exist in plants that are present in forages fed to horses. They may compete with 17-β estradiol and influence the estrous cycle. Therefore, the objective was to determine whether coumestrol from clover-mixed pastures is present in mare's plasma after their ingestion (experiment I), and when this phytoestrogen was present in mare's plasma after ingestion (experiment II). The effect of a long-term ingestion of phytoestrogens on estrous cycle disruption was assessed (experiment III; clinical case). Experiment I was carried out in nonpregnant anestrous and cyclic Lusitano mares (n = 14) kept on clover and grass-mixed pastures, and supplemented with concentrate and hay or cereal straw. Blood and feedstuff were obtained from November to March. In experiment II, stabled cyclic Lusitano mares (n = 6) were fed for 14 days with increasing amounts of alfalfa pellets (250 g to 1 kg/day). Sequential blood samples were obtained for 8 hours after feed intake on Day 0 (control) and on Days 13 and 14 (1 kg/day alfalfa pellets). Experiment III mares were fed with a mixture of alfalfa and clover haylage for 5 months (group 1; n = 4) or for 9 months (group 2; n = 12). Estrous cycle was determined on the basis of plasma estradiol (E2), progesterone (P4), and ultrasound (experiment III). Concentrations of phytoestrogen coumestrol and its metabolite methoxycoumestrol were determined by high-performance liquid chromatography coupled with mass spectrometry. Phytoestrogens decreased in pasture from November until March (P haylage) than in group 1, after haylage withdrawal (P < 0.001). These data show that in the mare, coumestrol and its metabolite increase in blood after ingestion of estrogenic plants and can influence reproduction in mares as potent endocrine disruptors. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Plasma cortisol and metabolite level profiles in two isogenic strains of common carp during confinement

    NARCIS (Netherlands)

    Ruane, N.M.; Huisman, E.A.; Komen, J.

    2001-01-01

    A rapid increase in common carp Cyprinus carpio plasma cortisol levels was noted, in two experiments, after 30 mins of a 3 h net confinement, which was sustained while the fish were held in the nets. After release from the nets, cortisol levels returned to control values in 1 h. Plasma glucose and

  19. Metabolomic profiles of arsenic (+3 oxidation state) methyltransferase knockout mice: Effect of sex and arsenic exposure

    Science.gov (United States)

    Huang, Madelyn C.; Douillet, Christelle; Su, Mingming; Zhou, Kejun; Wu, Tao; Chen, Wenlian; Galanko, Joseph A.; Drobná, Zuzana; Saunders, R. Jesse; Martin, Elizabeth; Fry, Rebecca C.; Jia, Wei; Stýblo, Miroslav

    2016-01-01

    Arsenic (+3 oxidation state) methyltransferase (As3mt) is the key enzyme in the pathway for methylation of inorganic arsenic (iAs). Altered As3mt expression and AS3MT polymorphism have been linked to changes in iAs metabolism and in susceptibility to iAs toxicity in laboratory models and in humans. As3mt-knockout mice have been used to study the association between iAs metabolism and adverse effects of iAs exposure. However, little is known about systemic changes in metabolism of these mice and how these changes lead to their increased susceptibility to iAs toxicity. Here, we compared plasma and urinary metabolomes of male and female wild-type (WT) and As3mt-KO (KO) C57BL6 mice and examined metabolomic shifts associated with iAs exposure in drinking water. Surprisingly, exposure to 1 ppm As elicited only small changes in the metabolite profiles of either WT or KO mice. In contrast, comparisons of KO mice with WT mice revealed significant differences in plasma and urinary metabolites associated with lipid (phosphatidylcholines, cytidine, acyl-carnitine), amino acid (hippuric acid, acetylglycine, urea), and carbohydrate (L-sorbose, galactonic acid, gluconic acid) metabolism. Notably, most of these differences were sex-specific. Sex-specific differences were also found between WT and KO mice in plasma triglyceride and lipoprotein cholesterol levels. Some of the differentially changed metabolites (phosphatidylcholines, carnosine, and sarcosine) are substrates or products of reactions catalyzed by other methyltransferases. These results suggest that As3mt KO alters major metabolic pathways in a sex-specific manner, independent of iAs treatment, and that As3mt may be involved in other cellular processes beyond iAs methylation. PMID:26883664

  20. A rapid method for simultaneous determination of arsenic, cadmium and lead in drinking water by inductively coupled plasma mass spectrometry

    Directory of Open Access Journals (Sweden)

    Joshua Rey P. Torres

    Full Text Available The raw water source of drinking water in most areas in the Philippines is typically river water and in some cases groundwater. These sources are prone to elevated levels of metals and metalloids that may cause exposure of the general population when the treatment of the water is inadequate. This work presents a simple method based on EPA Method 200.8 for the determination of total concentrations of arsenic (As, cadmium (Cd and lead (Pb in drinking water using inductively coupled plasma-mass spectrometry (ICP-MS as the element-selective detector. This was applied in the determination of these elements in the water supply in Metro Manila, Philippines. The method detection limits were 0.095 μg L-1, 0.043 μg L-1, and 0.114 μg L-1 for total As, Cd and Pb, respectively.The method was validated using National Institute of Standards and Technology (NIST 1643e certified reference material for trace elements in water and determined values were 60.4 ± 0.5 μg L-1, 6.7 ± 0.1 μg L-1, and 19.6 ± 0.5 μg L-1 for As, Cd and Pb, respectively. These determined values were in good agreement with the certified values in the reference material. Analysis of actual drinking water samples showed that most samples did not exceed the limit of the Philippine drinking water standard for the elements.

  1. Quantitative determination of amitriptyline and its metabolite in rat plasma by liquid chromatography-tandem mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Chae, Jungwoo; Baek, Inhwan; An, Junghwa; Kim, Eun Jung; Kwon, Kwangil [Chungnam National Univ., Daejeon (Korea, Republic of)

    2012-07-15

    A rapid, specific, and reliable LC-MS/MS-based bioanalytical method was developed and validated in rat plasma for the simultaneous quantitation of amitriptyline and its metabolite nortriptyline. Chromatographic separation of these analytes was achieved on a Gemini C18 column (50 X 4.60 mm, 5 {mu}m) using reversed-phase chromatography. The mobile phase was an isocratic solvent system consisting of 1% formic acid in water and methanol (10:90, v/v), at a flow rate of 0.2 mL/min. The analytical range was set as 0.1-500 ng/mL for amitriptyline and 0.08-500 ng/mL for nortriptyline using a 200 {mu}L plasma sample. The accuracy and precision of the assay were in accordance with FDA regulations for the validation of bioanalytical methods. The validated method was successfully applied to a pharmacokinetic study in six rats after oral administration of amitriptyline (15 mg/kg). This method allows laboratory scientists to rapidly determine amitriptyline and nortriptyline concentrations in plasma.

  2. Speciation of arsenic in marine food (Anemonia sulcata) by liquid chromatography coupled to inductively coupled plasma mass spectrometry and organic mass spectrometry.

    Science.gov (United States)

    Contreras-Acuña, M; García-Barrera, T; García-Sevillano, M A; Gómez-Ariza, J L

    2013-03-22

    Arsenic species have been investigated in Anemonia sulcata, which is frequently consumed food staple in Spain battered in wheat flour and fried with olive oil. Speciation in tissue extracts was carried out by anion/cation exchange chromatography with inductively coupled plasma mass spectrometry (HPLC-(AEC/CEC)-ICP-MS). Three methods for the extraction of arsenic species were investigated (ultrasonic bath, ultrasonic probe and focused microwave) and the optimal one was applied. Arsenic speciation was carried out in raw and cooked anemone and the dominant species are dimethylarsinic acid (DMA(V)) followed by arsenobetaine (AB), As(V), monomethylarsonic acid (MA(V)), tetramethylarsonium ion (TETRA) and trimethylarsine oxide (TMAO). In addition, arsenocholine (AsC), glyceryl phosphorylarsenocholine (GPAsC) and dimethylarsinothioic acid (DMAS) were identified by liquid chromatography coupled to triple quadrupole mass spectrometry (HPLC-MS). These results are interesting since GPAsC has been previously reported in marine organisms after experimental exposure to AsC, but not in natural samples. In addition, this paper reports for the first time the identification of DMAS in marine food. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Short-term effects of air temperature on plasma metabolite concentrations in patients undergoing cardiac catheterization

    International Nuclear Information System (INIS)

    Hampel, Regina; Breitner, Susanne; Kraus, William E.; Hauser, Elizabeth; Shah, Svati; Ward-Caviness, Cavin K.; Devlin, Robert; Diaz-Sanchez, David; Neas, Lucas; Cascio, Wayne; Peters, Annette; Schneider, Alexandra

    2016-01-01

    Background: Epidemiological studies have shown associations between air temperature and cardiovascular health outcomes. Metabolic dysregulation might also play a role in the development of cardiovascular disease. Objectives: To investigate short-term temperature effects on metabolites related to cardiovascular disease. Methods: Concentrations of 45 acylcarnitines, 15 amino acids, ketone bodies and total free fatty acids were available in 2869 participants from the CATHeterization GENetics cohort recruited at the Duke University Cardiac Catheterization Clinic (Durham, NC) between 2001 and 2007. Ten metabolites were selected based on quality criteria and cluster analysis. Daily averages of meteorological variables were obtained from the North American Regional Reanalysis project. Immediate, lagged, and cumulative temperature effects on metabolite concentrations were analyzed using (piecewise) linear regression models. Results: Linear temperature effects were found for glycine, C16-OH:C14:1-DC, and aspartic acid/asparagine. A 5 °C increase in temperature was associated with a 1.8% [95%-confidence interval: 0.3%; 3.3%] increase in glycine (5-day average), a 3.2% [0.1%; 6.3%] increase in C16-OH:C14:1-DC (lag of four days), and a −1.4% [−2.4%; −0.3%] decrease in aspartic acid/asparagine (lag of two days). Non-linear temperature effects were observed for alanine and total ketone bodies with breakpoint of 4 °C and 20 °C, respectively. Both a 5 °C decrease in temperature on colder days (<4 °C)and a 5 °C increase in temperature on warmer days (≥4 °C) were associated with a four day delayed increase in alanine by 6.6% [11.7; 1.8%] and 1.9% [0.3%; 3.4%], respectively. For ketone bodies we found immediate (0-day lag) increases of 4.2% [−0.5%; 9.1%] and 12.3% [0.1%; 26.0%] associated with 5 °C decreases on colder (<20 °C) days and 5 °C increases on warmer days (≥20 °C), respectively. Conclusions: We observed multiple effects of air temperature on

  4. Short-term effects of air temperature on plasma metabolite concentrations in patients undergoing cardiac catheterization

    Energy Technology Data Exchange (ETDEWEB)

    Hampel, Regina, E-mail: regina.hampel@helmholtz-muenchen.de [Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstraße 1, 85764 Neuherberg (Germany); Breitner, Susanne [Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstraße 1, 85764 Neuherberg (Germany); Kraus, William E. [School of Medicine, Duke University, Durham, NC 27701 (United States); Hauser, Elizabeth [School of Medicine, Duke University, Durham, NC 27701 (United States); Duke Molecular Physiology Institute, 300 North Duke Street, Durham, NC 27701 (United States); Cooperative Studies Program Epidemiology Center-Durham, Veterans Affairs Medical Center, Durham, NC 27701 (United States); Shah, Svati [School of Medicine, Duke University, Durham, NC 27701 (United States); Ward-Caviness, Cavin K. [Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstraße 1, 85764 Neuherberg (Germany); Devlin, Robert; Diaz-Sanchez, David; Neas, Lucas; Cascio, Wayne [National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, 109 T.W. Alexander Drive, Durham, NC 27709 (United States); Peters, Annette; Schneider, Alexandra [Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstraße 1, 85764 Neuherberg (Germany)

    2016-11-15

    Background: Epidemiological studies have shown associations between air temperature and cardiovascular health outcomes. Metabolic dysregulation might also play a role in the development of cardiovascular disease. Objectives: To investigate short-term temperature effects on metabolites related to cardiovascular disease. Methods: Concentrations of 45 acylcarnitines, 15 amino acids, ketone bodies and total free fatty acids were available in 2869 participants from the CATHeterization GENetics cohort recruited at the Duke University Cardiac Catheterization Clinic (Durham, NC) between 2001 and 2007. Ten metabolites were selected based on quality criteria and cluster analysis. Daily averages of meteorological variables were obtained from the North American Regional Reanalysis project. Immediate, lagged, and cumulative temperature effects on metabolite concentrations were analyzed using (piecewise) linear regression models. Results: Linear temperature effects were found for glycine, C16-OH:C14:1-DC, and aspartic acid/asparagine. A 5 °C increase in temperature was associated with a 1.8% [95%-confidence interval: 0.3%; 3.3%] increase in glycine (5-day average), a 3.2% [0.1%; 6.3%] increase in C16-OH:C14:1-DC (lag of four days), and a −1.4% [−2.4%; −0.3%] decrease in aspartic acid/asparagine (lag of two days). Non-linear temperature effects were observed for alanine and total ketone bodies with breakpoint of 4 °C and 20 °C, respectively. Both a 5 °C decrease in temperature on colder days (<4 °C)and a 5 °C increase in temperature on warmer days (≥4 °C) were associated with a four day delayed increase in alanine by 6.6% [11.7; 1.8%] and 1.9% [0.3%; 3.4%], respectively. For ketone bodies we found immediate (0-day lag) increases of 4.2% [−0.5%; 9.1%] and 12.3% [0.1%; 26.0%] associated with 5 °C decreases on colder (<20 °C) days and 5 °C increases on warmer days (≥20 °C), respectively. Conclusions: We observed multiple effects of air temperature on

  5. The concentration of plasma metabolites varies throughout reproduction and affects offspring number in wild brown trout (Salmo trutta).

    Science.gov (United States)

    Gauthey, Zoé; Freychet, Marine; Manicki, Aurélie; Herman, Alexandre; Lepais, Olivier; Panserat, Stéphane; Elosegi, Arturo; Tentelier, Cédric; Labonne, Jacques

    2015-06-01

    In wild populations, measuring energy invested in the reproduction and disentangling investment in gametes versus investment in reproductive behavior (such as intrasexual competition or intersexual preference) remain challenging. In this study, we investigated the energy expenditure in brown trout reproductive behavior by using two proxies: variation in weight and variation of plasma metabolites involved in energy production, over the course of reproductive season in a semi natural experimental river. We estimated overall reproductive success using genetic assignment at the end of the reproductive season. Results show that triglycerides and free fatty acid concentrations vary negatively during reproduction, while amino-acids and glucose concentrations remain stable. Decrease in triglyceride and free fatty acid concentrations during reproduction is not related to initial concentration levels or to weight variation. Both metabolite concentration variations and weight variations are correlated to the number of offspring produced, which could indicate that gametic and behavioral reproductive investments substantially contribute to reproductive success in wild brown trout. This study opens a path to further investigate variations in reproductive investment in wild populations. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Determination of psilocin, bufotenine, LSD and its metabolites in serum, plasma and urine by SPE-LC-MS/MS.

    Science.gov (United States)

    Martin, Rafaela; Schürenkamp, Jennifer; Gasse, Angela; Pfeiffer, Heidi; Köhler, Helga

    2013-05-01

    A validated method for the simultaneous determination of psilocin, bufotenine, lysergic acid diethylamide and its metabolites in serum, plasma and urine using liquid chromatography-electrospray ionization/tandem mass spectrometry was developed. During the solid-phase extraction procedure with polymeric mixed-mode cation exchange columns, the unstable analytes were protected by ascorbic acid, drying with nitrogen and exclusion of light. The limits of detection and quantitation for all analytes were low. Recovery was ≥86 % for all analytes and no significant matrix effects were observed. Interday and intraday imprecisions at different concentrations ranged from 1.1 to 8.2 % relative standard deviation, bias was within ±5.3 %. Processed samples were stable in the autosampler for at least 2 days. Furthermore, freeze/thaw and long-term stability were investigated. The method was successfully applied to authentic serum and urine samples.

  7. Arsenic species determination in human scalp hair by pressurized hot water extraction and high performance liquid chromatography-inductively coupled plasma-mass spectrometry.

    Science.gov (United States)

    Morado Piñeiro, Andrés; Moreda-Piñeiro, Jorge; Alonso-Rodríguez, Elia; López-Mahía, Purificación; Muniategui-Lorenzo, Soledad; Prada-Rodríguez, Darío

    2013-02-15

    Analytical methods for the determination of total arsenic and arsenic species (mainly As(III) and As(V)) in human scalp hair have been developed. Inductively coupled plasma-mass spectrometry (ICP-MS) and high performance liquid chromatography (HPLC) coupled to ICP-MS have been used for total arsenic and arsenic species determination, respectively. The proposed methods include a "green", fast, high efficient and automated species leaching procedure by pressurized hot water extraction (PHWE). The operating parameters for PHWE including modifier concentration, extraction temperature, static time, extraction steps, pressure, mean particle size, diatomaceous earth (DE) mass/sample mass ratio and flush volume were studied using design of experiments (Plackett-Burman design PBD). Optimum condition implies a modifier concentration (acetic acid) of 150 mM and powdered hair samples fully mixed with diatomaceous earth (DE) as a dispersing agent at a DE mass/sample mass ratio of 5. The extraction has been carried out at 100°C and at an extraction pressure of 1500 psi for 5 min in four extraction step. Under optimised conditions, limits of quantification of 7.0, 6.3 and 50.3 ng g(-1) for total As, As(III) and As(V), respectively were achieved. Repeatability of the overall procedure (4.4, 7.2 and 2.1% for total As, As(III) and As(V), respectively) was achieved. The analysis of GBW-07601 (human hair) certified reference material was used for validation. The optimised method has been finally applied to several human scalp hair samples. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Plasma metabolites associated with type 2 diabetes in a Swedish population: a case-control study nested in a prospective cohort.

    Science.gov (United States)

    Shi, Lin; Brunius, Carl; Lehtonen, Marko; Auriola, Seppo; Bergdahl, Ingvar A; Rolandsson, Olov; Hanhineva, Kati; Landberg, Rikard

    2018-04-01

    The aims of the present work were to identify plasma metabolites that predict future type 2 diabetes, to investigate the changes in identified metabolites among individuals who later did or did not develop type 2 diabetes over time, and to assess the extent to which inclusion of predictive metabolites could improve risk prediction. We established a nested case-control study within the Swedish prospective population-based Västerbotten Intervention Programme cohort. Using untargeted liquid chromatography-MS metabolomics, we analysed plasma samples from 503 case-control pairs at baseline (a median time of 7 years prior to diagnosis) and samples from a subset of 187 case-control pairs at 10 years of follow-up. Discriminative metabolites between cases and controls at baseline were optimally selected using a multivariate data analysis pipeline adapted for large-scale metabolomics. Conditional logistic regression was used to assess associations between discriminative metabolites and future type 2 diabetes, adjusting for several known risk factors. Reproducibility of identified metabolites was estimated by intra-class correlation over the 10 year period among the subset of healthy participants; their systematic changes over time in relation to diagnosis among those who developed type 2 diabetes were investigated using mixed models. Risk prediction performance of models made from different predictors was evaluated using area under the receiver operating characteristic curve, discrimination improvement index and net reclassification index. We identified 46 predictive plasma metabolites of type 2 diabetes. Among novel findings, phosphatidylcholines (PCs) containing odd-chain fatty acids (C19:1 and C17:0) and 2-hydroxyethanesulfonate were associated with the likelihood of developing type 2 diabetes; we also confirmed previously identified predictive biomarkers. Identified metabolites strongly correlated with insulin resistance and/or beta cell dysfunction. Of 46 identified

  9. Comparative kinetics of the turnover rates of vitamin D2 and vitamin D3 and their metabolites in chick plasma

    International Nuclear Information System (INIS)

    Hoy, D.A.; Horst, R.L.

    1986-01-01

    Studies regarding the discrimination between vitamin D 2 and vitamin D 3 by chickens have led to conflicting conclusions. To investigate this problem in more detail the authors administered radiolabeled vitamin D and vitamin D metabolites, which allowed them to determine their relative plasma clearance rates. The study involved 3 groups of adult male chickens (5/group). Group I received [ 3 H]-vitamin D 2 (1.2 Ci/mmole) and [ 3 H]-vitamin D 3 (1.2 Ci/mmole). Group II received [ 3 H]-25-OHD 2 (90 Ci/mmole) and [ 3 H]-25-OHD 3 (90 Ci/mmole). Group III received [ 3 H]-1,25-(OH) 2 D 3 (90 Ci/mmole) and [ 3 H]-1,25-(OH) 2 D 2 (90 Ci/mmole). The [ 3 H]-sterols were co-dosed within each group. The results indicated that the turnover rates of [ 3 H]-vitamin D 2 and [ 3 H]-vitamin D 3 were not significantly different. However, the plasma turnover of the 25 hydroxylated metabolites differed, with [ 3 H]-25-OHD 2 clearing faster (2-4X) than [ 3 H]-25-OHD 3 . The largest difference appeared in the 1,25-(OH) 2 D turnover rates with 1,25-(OH) 2 D 2 clearing approximately 10X faster than [ 3 H]-1,25-(OH) 2 D 3 . These data, therefore, indicate that discrimination against vitamin D 2 sterols in the chick occurs primarily between steps in the metabolism of vitamin D and not at the point of the parent vitamin

  10. Metabolic fingerprinting of high-fat plasma samples processed by centrifugation- and filtration-based protein precipitation delineates significant differences in metabolite information coverage.

    Science.gov (United States)

    Barri, Thaer; Holmer-Jensen, Jens; Hermansen, Kjeld; Dragsted, Lars O

    2012-03-09

    Metabolomics and metabolic fingerprinting are being extensively employed for improved understanding of biological changes induced by endogenous or exogenous factors. Blood serum or plasma samples are often employed for metabolomics studies. Plasma protein precipitation (PPP) is currently performed in most laboratories before LC-MS analysis. However, the impact of fat content in plasma samples on metabolite coverage has not previously been investigated. Here, we have studied whether PPP procedures influence coverage of plasma metabolites from high-fat plasma samples. An optimized UPLC-QTOF/MS metabolic fingerprinting approach and multivariate modeling (PCA and OPLS-DA) were utilized for finding characteristic metabolite changes induced by two PPP procedures; centrifugation and filtration. We used 12-h fasting samples and postprandial samples collected at 2h after a standardized high-fat protein-rich meal in obese non-diabetic subjects recruited in a dietary intervention. The two PPP procedures as well as external and internal standards (ISs) were used to track errors in response normalization and quantification. Remarkably and sometimes uniquely, the fPPP, but not the cPPP approach, recovered not only high molecular weight (HMW) lipophilic metabolites, but also small molecular weight (SMW) relatively polar metabolites. Characteristic SMW markers of postprandial samples were aromatic and branched-chain amino acids that were elevated (p<0.001) as a consequence of the protein challenge. In contrast, some HMW lipophilic species, e.g. acylcarnitines, were moderately lower (p<0.001) in postprandial samples. LysoPCs were largely unaffected. In conclusion, the fPPP procedure is recommended for processing high-fat plasma samples in metabolomics studies. While method improvements presented here were clear, use of several ISs revealed substantial challenges to untargeted metabolomics due to large and variable matrix effects. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Metabolite characterization of a novel sedative drug, remimazolam in human plasma and urine using ultra high-performance liquid chromatography coupled with synapt high-definition mass spectrometry.

    Science.gov (United States)

    Zhou, Ying; Hu, Pei; Jiang, Ji

    2017-04-15

    Remimazolam is a new chemical entity belonging to the benzodiazepine class of sedative drugs, which shows faster-acting onset and recovery than currently available short-acting sedatives. In the present study, ultra high performance liquid chromatography with synapt high-definition mass spectrometry method combined with MassLynx software was established to characterize metabolites of remimazolam in human plasma and urine. In total, 5 human metabolites were detected, including 3 phase I and 2 phase II metabolites. There was no novel human metabolite detected compared to that in rat. Hydrolysis, glucuronidation and oxidation were the major metabolic reactions. To our knowledge, this is the first report of the human metabolic profile of remimazolam. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Arsenic Methyltransferase

    Science.gov (United States)

    The metalloid arsenic enters the environment by natural processes (volcanic activity, weathering of rocks) and by human activity (mining, smelting, herbicides and pesticides). Although arsenic has been exploited for homicidal and suicidal purposes since antiquity, its significan...

  13. Plasma catecholamine metabolites in schizophrenics: evidence for the two-subtype concept.

    Science.gov (United States)

    Chang, W H; Chen, T Y; Lin, S K; Lung, F W; Lin, W L; Hu, W H; Yeh, E K

    1990-03-01

    Plasma homovanillic acid (pHVA) and plasma methoxyhydroxyphenyl glycol (pMHPG), as well as plasma haloperidol, were measured in 33 schizophrenic patients before and during 6 weeks of haloperidol treatment. Good responders had higher baseline pHVA values compared with poor responders (17.4 +/- 8.8 ng/ml, n = 22 versus 11.4 +/- 5.0 ng/ml, n = 11, p less than 0.05). A higher than 15 ng/ml pretreatment pHVA level was associated with a more consistent clinical response to the subsequent treatment. Differential pHVA changes during treatment were also found between good and poor responders. Within the good responder group, a significant decline in pHVA over time was found. By contrast, pHVA showed a transient increase in the poor responder group. Plasma MHPG changes showed a similar pattern during treatment in good responders, although no significant differences in baseline values were found between the good (n = 13) and poor (n = 9) responders, and pMHPG showed no change during treatment in poor responders. Significant correlations between baseline pHVA and pMHPG values were found in 22 patients. Good responders and poor responders did not differ significantly in terms of age, duration of illness, severity of presenting symptoms, haloperidol dose, or plasma drug concentration. Two hypothetical subtypes of schizophrenia and both dopamine and norepinephrine systems involved in schizophrenic psychopathology are proposed.

  14. Ultra high performance liquid chromatography-quadrupole-time of flight analysis for the identification and the determination of resveratrol and its metabolites in mouse plasma

    International Nuclear Information System (INIS)

    Menet, M.C.; Cottart, C.H.; Taghi, M.; Nivet-Antoine, V.; Dargère, D.

    2013-01-01

    Graphical abstract: Simultaneous identification and determination of new resveratrol metabolites in mice by UHPLC-Q-TOF in full scan mode. Highlights: ► Fast method to quantify resveratrol and its main metabolites in the mouse plasma. ► Isotope-labeled standards to build a linear calibration curve. ► Linear calibration curve on a wide range of concentrations. ► Simultaneous identification and quantification of metabolites by using full scan mode. ► Detection of uncommon metabolites not yet described in mice. - Abstract: Resveratrol is a polyphenol that has numerous interesting biological properties, but, per os, it is quickly metabolized. Some of its metabolites are more concentrated than resveratrol, may have greater biological activities, and may act as a kind of store for resveratrol. Thus, to understand the biological impact of resveratrol on a physiological system, it is crucial to simultaneously analyze resveratrol and its metabolites in plasma. This study presents an analytical method based on UHPLC-Q-TOF mass spectrometry for the quantification of resveratrol and of its most common hydrophilic metabolites. The use of 13 C- and D-labeled standards specific to each molecule led to a linear calibration curve on a larger concentration range than described previously. The use of high resolution mass spectrometry in the full scan mode enabled simultaneous identification and quantification of some hydrophilic metabolites not previously described in mice. In addition, UHPLC separation, allowing run times lower than 10 min, can be used in studies that requiring analysis of many samples.

  15. Ultra high performance liquid chromatography-quadrupole-time of flight analysis for the identification and the determination of resveratrol and its metabolites in mouse plasma

    Energy Technology Data Exchange (ETDEWEB)

    Menet, M.C., E-mail: marie-claude.menet@parisdescartes.fr [Universite Paris Descartes, Sorbonne Paris cite, EA 4463, Faculte des Sciences Pharmaceutiques et Biologiques, 4 avenue de l' Observatoire, Paris 75270 (France); Cottart, C.H. [APHP, Groupe hospitalier Pitie-Salpetriere, Charles Foix, Service de Biochimie, 7 avenue de la Republique, Ivry sur Seine 94205 (France); Universite Paris Descartes, Sorbonne Paris cite, EA 4466, Faculte des Sciences Pharmaceutiques et Biologiques, 4 avenue de l' Observatoire, Paris 75270 (France); Taghi, M. [Universite Paris Descartes, Sorbonne Paris cite, EA 4463, Faculte des Sciences Pharmaceutiques et Biologiques, 4 avenue de l' Observatoire, Paris 75270 (France); Nivet-Antoine, V. [Universite Paris Descartes, Sorbonne Paris cite, EA 4466, Faculte des Sciences Pharmaceutiques et Biologiques, 4 avenue de l' Observatoire, Paris 75270 (France); APHP, Hopital Europeen Georges Pompidou, Service de Biochimie, 20 rue Leblanc, Paris 75015 (France); Dargere, D. [Universite Paris Descartes, Sorbonne Paris cite, EA 4463, Faculte des Sciences Pharmaceutiques et Biologiques, 4 avenue de l' Observatoire, Paris 75270 (France); and others

    2013-01-25

    Graphical abstract: Simultaneous identification and determination of new resveratrol metabolites in mice by UHPLC-Q-TOF in full scan mode. Highlights: Black-Right-Pointing-Pointer Fast method to quantify resveratrol and its main metabolites in the mouse plasma. Black-Right-Pointing-Pointer Isotope-labeled standards to build a linear calibration curve. Black-Right-Pointing-Pointer Linear calibration curve on a wide range of concentrations. Black-Right-Pointing-Pointer Simultaneous identification and quantification of metabolites by using full scan mode. Black-Right-Pointing-Pointer Detection of uncommon metabolites not yet described in mice. - Abstract: Resveratrol is a polyphenol that has numerous interesting biological properties, but, per os, it is quickly metabolized. Some of its metabolites are more concentrated than resveratrol, may have greater biological activities, and may act as a kind of store for resveratrol. Thus, to understand the biological impact of resveratrol on a physiological system, it is crucial to simultaneously analyze resveratrol and its metabolites in plasma. This study presents an analytical method based on UHPLC-Q-TOF mass spectrometry for the quantification of resveratrol and of its most common hydrophilic metabolites. The use of {sup 13}C- and D-labeled standards specific to each molecule led to a linear calibration curve on a larger concentration range than described previously. The use of high resolution mass spectrometry in the full scan mode enabled simultaneous identification and quantification of some hydrophilic metabolites not previously described in mice. In addition, UHPLC separation, allowing run times lower than 10 min, can be used in studies that requiring analysis of many samples.

  16. Effects of vitamin D3 supplementation and UVb exposure on the growth and plasma concentration of vitamin D3 metabolites in juvenile bearded dragons (Pogona vitticeps)

    NARCIS (Netherlands)

    Oonincx, D.G.A.B.; Stevens, Y.; Borne, van den J.J.G.C.; Leeuwen, van J.P.T.M.; Hendriks, W.H.

    2010-01-01

    The effectiveness of dietary vitamin D3 and UVb exposure on plasma vitamin D metabolites in growing bearded dragons (Pogona vitticeps) was studied. A total of 84 (40 males and 44 females) newly hatched bearded dragons were allocated to six levels of oral vitamin D3 supplementation (0 to 400%) or six

  17. Blood Pressure Associated with Arsenic Methylation and Arsenic Metabolism Caused by Chronic Exposure to Arsenic in Tube Well Water.

    Science.gov (United States)

    Wei, Bing Gan; Ye, Bi Xiong; Yu, Jiang Ping; Yang, Lin Sheng; Li, Hai Rong; Xia, Ya Juan; Wu, Ke Gong

    2017-05-01

    The effects of arsenic exposure from drinking water, arsenic metabolism, and arsenic methylation on blood pressure (BP) were observed in this study. The BP and arsenic species of 560 participants were determined. Logistic regression analysis was applied to estimate the odds ratios of BP associated with arsenic metabolites and arsenic methylation capability. BP was positively associated with cumulative arsenic exposure (CAE). Subjects with abnormal diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse pressure (PP) usually had higher urinary iAs (inorganic arsenic), MMA (monomethylated arsenic), DMA (dimethylated arsenic), and TAs (total arsenic) than subjects with normal DBP, SBP, and PP. The iAs%, MMA%, and DMA% differed slightly between subjects with abnormal BP and those with normal BP. The PMI and SMI were slightly higher in subjects with abnormal PP than in those with normal PP. Our findings suggest that higher CAE may elevate BP. Males may have a higher risk of abnormal DBP, whereas females have a higher risk of abnormal SBP and PP. Higher urinary iAs may increase the risk of abnormal BP. Lower PMI may elevate the BP. However, higher SMI may increase the DBP and SBP, and lower SMI may elevate the PP. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  18. Understanding arsenic metabolism through spectroscopic determination of arsenic in human urine

    OpenAIRE

    Brima, Eid I.; Jenkins, Richard O.; Haris, Parvez I.

    2006-01-01

    In this review we discuss a range of spectroscopic techniques that are currently used for analysis of arsenic in human urine for understanding arsenic metabolism and toxicity, especially in relation to genetics/ethnicity, ingestion studies and exposure to arsenic through drinking water and diet. Spectroscopic techniques used for analysis of arsenic in human urine include inductively coupled plasma mass spectrometry (ICP-MS), hydride generation atomic absorption spectrometry (HG-AAS), hydride ...

  19. Simultaneous determination of tryptophan and 8 metabolites in human plasma by liquid chromatography/tandem mass spectrometry.

    Science.gov (United States)

    Boulet, Lysiane; Faure, Patrice; Flore, Patrice; Montérémal, Julien; Ducros, Véronique

    2017-06-01

    Tryptophan (Trp) is an essential amino-acid and the precursor of many biologically active substances such as kynurenine (KYN) and serotonin (5HT). Its metabolism is involved in different physiopathological states, such as cardiovascular diseases, cancer, immunomodulation or depression. Hence, the quantification of Trp catabolites, from both KYN and 5HT pathways, might be usefulfor the discovery of novel diagnostic and follow-up biomarkers. We have developed a simple method for quantification of Trp and 8 of its metabolites,involved in both KYN and 5HT pathways, using liquid chromatography coupled to tandem mass spectrometry. We also validated the methodin human plasma samples, according to NF EN ISO 15189 criteria. Our method shows acceptable intra- and inter-day coefficients of variation (CV) (<12% and <16% respectively). The linearity entirelycovers the human plasma range. Stabilities of whole blood and of residues weredetermined, as well as the use of 2 different types of collectiontube, enabling us to adapt our process. Matrix effects and reference values showed good agreement compared to the literature. We propose here a method allowing the simultaneous quantification of a panel of Trp catabolites, never used before to our knowledge. This method, witha quickchromatographic runtime (15min) and simple sample preparation, has beenvalidated according to NF EN ISO 15189 criteria. The method enables the detailed analysis of these metabolic pathways, which are thought to be involved in a number of pathological conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Feeding motivation and plasma metabolites in pregnant sows fed diets rich in dietary fiber either once or twice daily.

    Science.gov (United States)

    Jensen, M B; Pedersen, L J; Theil, P K; Yde, C C; Bach Knudsen, K E

    2012-06-01

    The present study investigated the effects of source and level of dietary fiber (DF) and feeding frequency (once vs. twice daily) on feeding motivation and plasma metabolites at 4 different time points post feeding. Sixty pregnant sows (Sus scrofa, 4 blocks of 15 sows) were allocated to 1 of 5 diets within blocks. Four diets were restricted (approximately 35 MJ ME/d): a barley and wheat control diet (171 g DF/kg DM; 12 g DF/MJ ME), and 3 fiber diets formulated to contain 35% DF by including pectin residue (323 g DF/kg DM; 25 g DF/MJ ME), potato pulp (404 g DF/kg DM; 29 g DF/MJ ME), or sugar beet pulp (367 g DF/kg DM; 25 g DF/MJ ME). The fifth diet was a mixture including an equal amount of the 3 fiber diets offered semi ad libitum (ad libitum access to feed during 6 periods of 1 h starting at 0300, 0600, 1100, 1500, 1800, and 2300; 354 g DF/kg DM; 25 g DF/MJ ME). The experimental period included 2 periods of 4 wk each. Restricted-fed sows were fed once daily (0800 h) during the first period and twice daily (0800 and 1500 h) during the second period, or vice versa. Semi ad libitum fed sows had access to feed 6 times a day in both periods. In each period, the feeding motivation was assessed in an operant conditioning test, and samples of peripheral blood were taken in a balanced design, at 0900, 1200, 1900, and 0700 h, corresponding to 1, 4, 11, and 23 h after feeding for restricted sows fed once daily. No differences in the feeding motivation were found between the 4 restricted diets at any of the time points post feeding, but semi ad libitum fed sows had a decreased feeding motivation (P motivation at 1900 h (P motivation during the night compared with feeding once daily. Among restricted-fed sows, plasma concentrations of short-chain fatty acids (SCFA) were greater in sows fed high-fiber diets compared with the control (P = 0.02). Nonesterified fatty acid was least in sows on the control diet and greatest in sows on the potato diet, whereas sows on the pectin and

  1. Fast Determination of Toxic Arsenic Species in Food Samples Using Narrow-bore High-Performance Liquid-Chromatography Inductively Coupled Plasma Mass Spectrometry.

    Science.gov (United States)

    Terol, Amanda; Marcinkowska, Monika; Ardini, Francisco; Grotti, Marco

    2016-01-01

    A new method for the speciation analysis of arsenic in food using narrow-bore high-performance liquid-chromatography inductively coupled plasma mass spectrometry (HPLC-ICP-MS) has been developed. Fast separation of arsenite, arsenate, monomethylarsonic acid and dimethylarsinic acid was carried out in 7 min using an anion-exchange narrow-bore Nucleosil 100 SB column and 12 mM ammonium dihydrogen phosphate of pH 5.2 as the mobile phase, at a flow rate of 0.3 mL min(-1). A PFA-ST micronebulizer jointed to a cyclonic spray chamber was used for HPLC-ICP-MS coupling. Compared with standard-bore HPLC-ICP-MS, the new method has provided higher sensitivity, reduced mobile-phase consumption, a lower matrix plasma load and a shorter analysis time. The achieved instrumental limits of detection were in the 0.3 - 0.4 ng As mL(-1) range, and the precision was better than 3%. The arsenic compounds were efficiently (>80%) extracted from various food samples using a 1:5 methanol/water solution, with additional ultrasonic treatment for rice products. The applicability of this method was demonstrated by the analysis of several samples, such as seafood (fish, mussels, shrimps, edible algae) and rice-based products (Jasmine and Arborio rice, spaghetti, flour, crackers), including three certified reference materials.

  2. The metabolite generated by dipeptidyl-peptidase 4 metabolism of glucagon-like peptide-1 has no influence on plasma glucose levels in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Zander, M; Madsbad, S; Deacon, C F

    2006-01-01

    AIM/HYPOTHESIS: Glucagon-like peptide-1 (GLP-1) is metabolised by the enzyme dipeptidyl-peptidase 4 (DPP-4), generating a metabolite with potential antagonistic properties. This study was conducted to evaluate the effect of that metabolite on plasma glucose levels in patients with type 2 diabetes...... of the metabolite increased from 1+/-3 (SAL) and 2+/-6 (IB) pmol/l to 42+/-4 (LSC), 64+/-8 (IV) and 327+/-16 (HSC) pmol/l, pglucose levels at 6 h decreased from 12.4+/-1.1 (SAL) mmol/l to 10.4+/-1.1 (LSC), 8.6+/-0.6 (IB), 8.8+/-0.8 (IV) and 9.1+/-0.9 (HSC) mmol/l, p.../INTERPRETATION: At approximately similar concentrations of intact GLP-1 (IV, IB, HSC), but with widely ranging metabolite concentrations, the effect on plasma glucose levels was equal, indicating that the presence of the metabolite does not antagonise the glucose-lowering effect of GLP-1....

  3. Profile of plasma and urine metabolites after the intake of almond [Prunus dulcis (Mill.) D.A. Webb] polyphenols in humans.

    Science.gov (United States)

    Urpi-Sarda, Mireia; Garrido, Ignacio; Monagas, María; Gómez-Cordovés, Carmen; Medina-Remón, Alexander; Andres-Lacueva, Cristina; Bartolomé, Begoña

    2009-11-11

    Nut skins are considered to be a rich source of polyphenols and may be partially responsible for the numerous health effects associated with nut consumption. However, more bioavailability studies of nut skin polyphenols are needed to understand the health effects derived from nut consumption. The aim of the present study was to determine the profiles of both phase II and microbial-derived phenolic metabolites in plasma and urine samples before and after the intake of almond skin polyphenols by healthy human subjects (n = 2). Glucuronide, O-methyl glucuronide, sulfate, and O-methyl sulfate derivatives of (epi)catechin, as well as the glucuronide conjugates of naringenin and glucuronide and sulfate conjugates of isorhamnetin, were detected in plasma and urine samples after consumption of almond skin polyphenols. The main microbial-derived metabolites of flavanols, such as 5-(dihydroxyphenyl)-gamma-valerolactone and 5-(hydroxymethoxyphenyl)-gamma-valerolactone, were also detected in their glucuronide and sulfate forms. In addition, numerous metabolites derived from further microbial degradation of hydroxyphenylvalerolactones, including hydroxyphenylpropionic, hydroxyphenylacetic, hydroxycinnamic, hydroxybenzoic, and hydroxyhippuric acids, registered major changes in urine after the consumption of almond skin polyphenols. The urinary excretion of these microbial metabolites was estimated to account for a larger proportion of the total polyphenol ingested than phase II metabolites of (epi)catechin, indicating the important role of intestinal bacteria in the metabolism of highly polymerized almond skin polyphenols. To the authors' knowledge this study constitutes the most complete report of the absorption of almond skin polyphenols in humans.

  4. Low plasma cortisol and fecal cortisol metabolite measures as indicators of compromised welfare in domestic horses (Equus caballus.

    Directory of Open Access Journals (Sweden)

    Jodi Pawluski

    Full Text Available The hypothalamic-pituitary-adrenal (HPA axis response to chronic stress is far from straight forward, particularly with regards to animal welfare. There are reports of no effect as well as both decreases and increases in cortisol after chronic stressors. Therefore, the first aim of the present study was to determine how measures of compromised welfare, such as chronic pain and haematological anomalies, related to cortisol levels in domestic horses (Equus caballus. Domestic horses are an informative model to investigate the impact of chronic stress (due to environment, pain, work, housing conditions… on the HPA axis. The second aim was to determine whether levels of fecal cortisol metabolites (FCM may be used as an indicator of welfare measures. The present study used fifty-nine horses (44 geldings and 15 mares, from three riding centres in Brittany, France. The primary findings show that horses whose welfare was clearly compromised (as indicated by an unusual ears backward position, presence of vertebral problems or haematological anomalies, e.g. anaemia also had lower levels of both FCM and plasma cortisol. This work extends our previous findings showing that withdrawn postures, indicators of depressive-like behavior in horses, are associated with lower plasma cortisol levels. We also found that evening plasma cortisol levels positively correlated with FCM levels in horses. Future research aims to determine the extent to which factors of influence on welfare, such as living conditions (e.g. single stalls versus group housing in pasture or paddocks, early life factors, and human interaction, act as mediators of cortisol levels in horses.

  5. A validated HPLC-MS/MS assay for quantifying unstable pharmacologically active metabolites of clopidogrel in human plasma: application to a clinical pharmacokinetic study.

    Science.gov (United States)

    Furlong, Michael T; Savant, Ishani; Yuan, Moucun; Scott, Laura; Mylott, William; Mariannino, Thomas; Kadiyala, Pathanjali; Roongta, Vikram; Arnold, Mark E

    2013-05-01

    Clopidogrel is prescribed for the treatment of Acute Coronary Syndrome and recent myocardial infarction, recent stroke, or established peripheral arterial disease. A sensitive and reliable high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay was developed and validated to enable reliable quantification of four diastereomeric and chemically reactive thiol metabolites, two of which are pharmacologically active, in human plasma. The metabolites were stabilized by alkylation of their reactive thiol moieties with 2-bromo-3'-methoxyacetophenone (MPB). Following organic solvent mediated-protein precipitation in a 96-well plate format, chromatographic separation was achieved by gradient elution on an Ascentis Express RP-amide column. Chromatographic conditions were optimized to ensure separation of the four derivatized active metabolites. Derivatized metabolites and stable isotope-labeled internal standards were detected by positive ion electrospray tandem mass spectrometry. The HPLC-MS/MS assay was validated over concentration ranges of 0.125-125 ng/mL for metabolites H1-H3 and 0.101-101 ng/mL for H4. Intra- and inter-assay precision values for replicate quality control samples were within 14.3% for all analytes during the assay validation. Mean quality control accuracy values were within ±6.3% of nominal values for all analytes. Assay recoveries were high (>79%). The four derivatized analytes were stable in human blood for at least 2 h at room temperature and on ice. The analytes were also stable in human plasma for at least 25 h at room temperature, 372 days at -20 °C and -70 °C, and following at least five freeze-thaw cycles. The validated assay was successfully applied to the quantification of all four thiol metabolites in human plasma in support of a human pharmacokinetic study. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Routine determination of [18F]-L-6-fluorodopa and its metabolites in blood plasma is essential for accurate positron emission tomography studies

    International Nuclear Information System (INIS)

    Chan, G.L.Y.; Hewitt, K.A.; Pate, B.D.; Schofield, P.; Adam, M.J.; Ruth, T.J.

    1991-01-01

    A batch-contact alumina-extraction method has been used to separate [ 18 F]-L-6-fluorodopa (FD) from its principal metabolite, 3-O-methyl-[ 18 F]-6 fluorodopa (3-OMe-FD), in arterial blood plasma samples collected from subjects pretreated with carbidopa during positron emission tomography (PET) scans. The time course of the metabolite-corrected blood plasma activity is then used as an input function for kinetic analysis of striatal FD uptake. Results obtained from using the batch-contact alumina-extraction method were compared with those from high performance liquid chromatography, and also with those from a chromatographic alumina cartridge technique. In 60 human subjects including normal healthy volunteers and patients diagnoses as having a movement disorder, arterial blood plasma samples were collected after FD injection during a two-hour PET scan and analyzed by the batch-contact alumina-extraction method. The activity ratio (metabolites/FD) increased linearly with time for all subjects. However, there was a wide variation in the slope of the plot of the activity ratio versus time among the subjects. No significant linear or curved relationship was observed between the slope and the age of the subject. Separation of FD from its metabolites is therefore, necessary for each PET-FD study conducted

  7. A diet rich in high-glucoraphanin broccoli interacts with genotype to reduce discordance in plasma metabolite profiles by modulating mitochondrial function123

    Science.gov (United States)

    Armah, Charlotte N; Traka, Maria H; Dainty, Jack R; Defernez, Marianne; Janssens, Astrid; Leung, Wing; Doleman, Joanne F; Potter, John F

    2013-01-01

    Background: Observational and experimental studies suggest that diets rich in cruciferous vegetables and glucosinolates may reduce the risk of cancer and cardiovascular disease (CVD). Objective: We tested the hypothesis that a 12-wk dietary intervention with high-glucoraphanin (HG) broccoli would modify biomarkers of CVD risk and plasma metabolite profiles to a greater extent than interventions with standard broccoli or peas. Design: Subjects were randomly assigned to consume 400 g standard broccoli, 400 g HG broccoli, or 400 g peas each week for 12 wk, with no other dietary restrictions. Biomarkers of CVD risk and 347 plasma metabolites were quantified before and after the intervention. Results: No significant differences in the effects of the diets on biomarkers of CVD risk were found. Multivariate analyses of plasma metabolites identified 2 discrete phenotypic responses to diet in individuals within the HG broccoli arm, differentiated by single nucleotide polymorphisms associated with the PAPOLG gene. Univariate analysis showed effects of sex (P broccoli arm, the consequence of the intervention was to reduce variation in lipid and amino acid metabolites, tricarboxylic acid (TCA) cycle intermediates, and acylcarnitines between the 2 PAPOLG genotypes. Conclusions: The metabolic changes observed with the HG broccoli diet are consistent with a rebalancing of anaplerotic and cataplerotic reactions and enhanced integration of fatty acid β-oxidation with TCA cycle activity. These modifications may contribute to the reduction in cancer risk associated with diets that are rich in cruciferous vegetables. This trial was registered at clinicaltrials.gov as NCT01114399. PMID:23964055

  8. Determination of the Cyanide Metabolite 2-Aminothiazoline-4-Carboxylic Acid in Urine and Plasma by Gas Chromatography-Mass Spectrometry

    National Research Council Canada - National Science Library

    Logue, Brian A; Kirschten, Nicholas P; Petrikovics, Ilona; Moser, Matthew A; Rockwood, Gary A; Baskin, Steven I

    2005-01-01

    The cyanide metabolite 2-aminothiazoline.4-carboxylic acid (ATCA) is a promising biomarker for cyanide exposure because of its stability and the limitations of direct determination of cyanide and more abundant cyanide metabolites...

  9. Impaired arsenic metabolism in children during weaning

    International Nuclear Information System (INIS)

    Faengstroem, Britta; Hamadani, Jena; Nermell, Barbro; Grander, Margaretha; Palm, Brita; Vahter, Marie

    2009-01-01

    Background: Methylation of inorganic arsenic (iAs) via one-carbon metabolism is a susceptibility factor for a range of arsenic-related health effects, but there is no data on the importance of arsenic metabolism for effects on child development. Aim: To elucidate the development of arsenic metabolism in early childhood. Methods: We measured iAs, methylarsonic acid (MA) and dimethylarsinic acid (DMA), the metabolites of iAs, in spot urine samples of 2400 children at 18 months of age. The children were born to women participating in a population-based longitudinal study of arsenic effects on pregnancy outcomes and child development, carried out in Matlab, a rural area in Bangladesh with a wide range of arsenic concentrations in drinking water. Arsenic metabolism was evaluated in relation to age, sex, anthropometry, socio-economic status and arsenic exposure. Results: Arsenic concentrations in child urine (median 34 μg/L, range 2.4-940 μg/L), adjusted to average specific gravity of 1.009 g/mL, were considerably higher than that measured at 3 months of age, but lower than that in maternal urine. Child urine contained on average 12% iAs, 9.4% MA and 78% DMA, which implies a marked change in metabolite pattern since infancy. In particular, there was a marked increase in urinary %MA, which has been associated with increased risk of health effects. Conclusion: The arsenic metabolite pattern in urine of children at 18 months of age in rural Bangladesh indicates a marked decrease in arsenic methylation efficiency during weaning.

  10. Rapid solid-phase extraction method to quantify [11C]-verapamil, and its [11C]-metabolites, in human and macaque plasma

    International Nuclear Information System (INIS)

    Unadkat, Jashvant D.; Chung, Francisco; Sasongko, Lucy; Whittington, Dale; Eyal, Sara; Mankoff, David; Collier, Ann C.; Muzi, Mark; Link, Jeanne

    2008-01-01

    Introduction: P-glycoprotein (P-gp), an efflux transporter, is a significant barrier to drug entry into the brain and the fetus. The positron emission tomography (PET) ligand, [ 11 C]-verapamil, has been used to measure in vivo P-gp activity at various tissue-blood barriers of humans and animals. Since verapamil is extensively metabolized in vivo, it is important to quantify the extent of verapamil metabolism in order to interpret such P-gp activity. Therefore, we developed a rapid solid-phase extraction (SPE) method to separate, and then quantify, verapamil and its radiolabeled metabolites in plasma. Methods: Using high-performance liquid chromatography (HPLC), we established that the major identifiable circulating radioactive metabolite of [ 11 C]-verapamil in plasma of humans and the nonhuman primate, Macaca nemestrina, was [ 11 C]-D-617/717. Using sequential and differential pH elution on C 8 SPE cartridges, we developed a rapid method to separate [ 11 C]-verapamil and [ 11 C]-D-617/717. Recovery was measured by spiking the samples with the corresponding nonradioactive compounds and assaying these compounds by HPLC. Results: Verapamil and D-617/717 recovery with the SPE method was >85%. When the method was applied to PET studies in humans and nonhuman primates, significant plasma concentration of D-617/717 and unknown polar metabolite(s) were observed. The SPE and the HPLC methods were not significantly different in the quantification of verapamil and D-617/717. Conclusions: The SPE method simultaneously processes multiple samples in less than 5 min. Given the short half-life of [ 11 C], this method provides a valuable tool to rapidly determine the concentration of [ 11 C]-verapamil and its [ 11 C]-metabolites in human and nonhuman primate plasma

  11. Rapid solid-phase extraction method to quantify [{sup 11}C]-verapamil, and its [{sup 11}C]-metabolites, in human and macaque plasma

    Energy Technology Data Exchange (ETDEWEB)

    Unadkat, Jashvant D. [Department of Pharmaceutics, University of Washington, Box 357610, Seattle, WA 98195 (United States)], E-mail: jash@u.washington.edu; Chung, Francisco; Sasongko, Lucy; Whittington, Dale; Eyal, Sara [Department of Pharmaceutics, University of Washington, Box 357610, Seattle, WA 98195 (United States); Mankoff, David [Department of Radiology, University of Washington, Box 356004, Seattle, WA 98195 (United States); Collier, Ann C. [Department of Medicine, University of Washington, Box 359929, Seattle, WA 98195 (United States); Muzi, Mark; Link, Jeanne [Department of Radiology, University of Washington, Box 356004, Seattle, WA 98195 (United States)

    2008-11-15

    Introduction: P-glycoprotein (P-gp), an efflux transporter, is a significant barrier to drug entry into the brain and the fetus. The positron emission tomography (PET) ligand, [{sup 11}C]-verapamil, has been used to measure in vivo P-gp activity at various tissue-blood barriers of humans and animals. Since verapamil is extensively metabolized in vivo, it is important to quantify the extent of verapamil metabolism in order to interpret such P-gp activity. Therefore, we developed a rapid solid-phase extraction (SPE) method to separate, and then quantify, verapamil and its radiolabeled metabolites in plasma. Methods: Using high-performance liquid chromatography (HPLC), we established that the major identifiable circulating radioactive metabolite of [{sup 11}C]-verapamil in plasma of humans and the nonhuman primate, Macaca nemestrina, was [{sup 11}C]-D-617/717. Using sequential and differential pH elution on C{sub 8} SPE cartridges, we developed a rapid method to separate [{sup 11}C]-verapamil and [{sup 11}C]-D-617/717. Recovery was measured by spiking the samples with the corresponding nonradioactive compounds and assaying these compounds by HPLC. Results: Verapamil and D-617/717 recovery with the SPE method was >85%. When the method was applied to PET studies in humans and nonhuman primates, significant plasma concentration of D-617/717 and unknown polar metabolite(s) were observed. The SPE and the HPLC methods were not significantly different in the quantification of verapamil and D-617/717. Conclusions: The SPE method simultaneously processes multiple samples in less than 5 min. Given the short half-life of [{sup 11}C], this method provides a valuable tool to rapidly determine the concentration of [{sup 11}C]-verapamil and its [{sup 11}C]-metabolites in human and nonhuman primate plasma.

  12. SPECIATION OF SELENIUM AND ARSENIC COMPOUNDS BY CAPILLARY ELECTROPHORESIS WITH HYDRODYNAMICALLY MODIFIED ELECTROOSMOTIC FLOW AND ON-LINE REDUCTION OF SELENIUM(VI) TO SELENIUM(IV) WITH HYDRIDE GENERATION INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRIC DETECTION

    Science.gov (United States)

    Capillary electrophoresis (CE) with hydride generation inductively coupled plasma mass spectrometry was used to determine four arsenicals and two selenium species. Selenate (SeVI) was reduced on-line to selenite (SeIV') by mixing the CE effluent with concentrated HCl. A microporo...

  13. Evolution of arsenic in high fluence plasma immersion ion implanted silicon : Behavior of the as-implanted surface

    NARCIS (Netherlands)

    Vishwanath, V.; Demenev, E.; Giubertoni, D.; Vanzetti, L.; Koh, A. L.; Steinhauser, G.; Pepponi, G.; Bersani, M.; Meirer, F.; Foad, M. A.

    2015-01-01

    High fluence (>1015 ions/cm2) low-energy (3 + on (1 0 0) silicon was investigated, with the focus on stability and retention of the dopant. At this dose, a thin (∼3 nm) amorphous layer forms at the surface, which contains about 45% arsenic (As) in a silicon and oxygen matrix. The presence of silicon

  14. The impact of BMI on sperm parameters and the metabolite changes of seminal plasma concomitantly.

    Science.gov (United States)

    Guo, Dan; Wu, Wei; Tang, Qiuqin; Qiao, Shanlei; Chen, Yiqiu; Chen, Minjian; Teng, Mengying; Lu, Chuncheng; Ding, Hongjuan; Xia, Yankai; Hu, Lingqing; Chen, Daozhen; Sha, Jiahao; Wang, Xinru

    2017-07-25

    The development of male infertility increased rapidly worldwide, which coinciding with the epidemic of obesity. However, the impact of weight abnormalities on sperm quality is still contestable. To assess the correlation between BMI and sperm parameters, we searched relevant articles in PubMed, Embase, Web of science, and Wanfang database published until June 2015 without language restriction. Otherwise, we also recruited some participants who attended fertility clinic as well as some general populations in this report. We performed a systematic review and meta-analysis about BMI and sperm parameters containing total sperm count, concentration, semen volume and sperm motility (overall and progressive). Metabolomic analysis of seminal plasma was performed to explore the mechanism from a new perspective. This study found standardized weighted mean differences (SMD) in sperm parameters (total sperm count, sperm concentration, and semen volume) of abnormal weight groups decreased to different degree compared to normal weight. Dose-response analysis found SMD of sperm count, sperm concentration and semen volume respectively fell 2.4%, 1.3% and 2.0% compared with normal weight for every 5-unit increase in BMI. Metabolomic analysis of seminal plasma showed that spermidine and spermine were likely to play a vital role in the spermatogenesis progress. This systematic review with meta-analysis has confirmed there was a relationship between BMI and sperm quality, suggesting obesity may be a detrimental factor of male infertility.

  15. Simultaneous Determination of 6-Mercaptopurine and its Oxidative Metabolites in Synthetic Solutions and Human Plasma using Spectrophotometric Multivariate Calibration Methods

    Directory of Open Access Journals (Sweden)

    Mohammad-Reza Rashidi

    2011-06-01

    Full Text Available Introduction: 6-Mercaptopurine (6MP is an important chemotherapeutic drug in the conventional treatment of childhood acute lymphoblastic leukemia (ALL. It is catabolized to 6-thiouric acid (6TUA through 8-hydroxo-6-mercaptopurine (8OH6MP or 6-thioxanthine (6TX intermediates. Methods: High-performance liquid chromatography (HPLC is usually used to determine the contents of therapeutic drugs, metabolites and other important biomedical analytes in biological samples. In the present study, the multivariate calibration methods, partial least squares (PLS-1 and principle component regression (PCR have been developed and validated for the simultaneous determination of 6MP and its oxidative metabolites (6TUA, 8OH6MP and 6TX without analyte separation in spiked human plasma. Mixtures of 6MP, 8-8OH6MP, 6TX and 6TUA have been resolved by PLS-1 and PCR to their UV spectra. Results: Recoveries (% obtained for 6MP, 8-8OH6MP, 6TX and 6TUA were 94.5-97.5, 96.6-103.3, 95.1-96.9 and 93.4-95.8, respectively, using PLS-1 and 96.7-101.3, 96.2-98.8, 95.8-103.3 and 94.3-106.1, respectively, using PCR. The NAS (Net analyte signal concept was used to calculate multivariate analytical figures of merit such as limit of detection (LOD, selectivity and sensitivity. The limit of detections for 6MP, 8-8OH6MP, 6TX and 6TUA were calculated to be 0.734, 0.439, 0.797 and 0.482 µmol L-1, respectively, using PLS and 0.724, 0.418, 0783 and 0.535 µmol L-1, respectively, using PCR. HPLC was also applied as a validation method for simultaneous determination of these thiopurines in the synthetic solutions and human plasma. Conclusion: Combination of spectroscopic techniques and chemometric methods (PLS and PCR has provided a simple but powerful method for simultaneous analysis of multicomponent mixtures.

  16. Simultaneous quantification of MTC-220 and its metabolites in beagle dog plasma by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Liu, Xin; Zhao, Manman; Mi, Jiaqi; Liu, Zhihao; Hu, Jinping; Sheng, Li; Wang, Baolian; Li, Dan; Yang, Shuang; Li, Yan

    2014-10-01

    A sensitive LC-ESI-MS/MS method for simultaneous determination of MTC-220 and its metabolites (paclitaxel and MDA-linker) in dog plasma has been developed and validated. After addition of docetaxel (internal standard), plasma samples containing MTC-220, paclitaxel and MDA-linker were prepared based on a simple protein precipitation by adding two volumes of acetonitrile. The separation was performed on a ZorbaxSB-C18 column (3.5μm, 2.1mm×100mm) at a flow rate of 0.2ml/min, using acetonitrile/water containing 0.1% formic acid (v/v) as mobile phase. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization (ESI) by selected reaction monitoring (SRM). The MS/MS ion transit ions monitored were 1444.4→623.8 for MTC-220, 876.4→307.9 for paclitaxel, 631.2→531.2 for MDA-linker and 830.2→549.1 for the internal standard. Linear detection responses were obtained for MTC-220, paclitaxel and MDA-linker ranging from 10 to 5000, 5 to 2500 and 5 to 500ng/ml, respectively. The lower limits of quantitation (LLOQs) for MTC-220, paclitaxel and MDA-linker were 10, 5 and 5ng/ml, respectively. The intra-day and inter-day precisions (RSD, %) of the three analytes do not exceed 10.9% except for LLOQs (≤17.50), and the accuracy (RE, %) were within ±17.5% for LLOQs and ±12.6% for the others. The average recoveries of three compounds were greater than 85.0%. The analytes were proved to be stable during all sample storage, preparation and analytic procedures. The validated method was successfully applied to pharmacokinetic studies of MTC-220 and its metabolites in beagle dogs after intravenous infusion of MTC-220 at 2.5mg/kg. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Plasma transport of ergocalciferol and cholecalciferol and their 25-hydroxylated metabolites in dairy cows

    DEFF Research Database (Denmark)

    Hymøller, Lone; Jensen, Søren Krogh

    2017-01-01

    treatments: D2, housed indoor and fed 625-μg/d (25.000 IU) ERG; D3, housed indoor and fed 625-μg/d CHO; D2+D3, housed indoor and fed 625-μg/d ERG and 625-μg/d CHO; SUN, let out for daily pasture to facilitate CHO synthesis from sunlight; and D2+SUN, fed 625-μg/d ERG and let out for daily pasture. Blood....../mL 25CHO in pasture or CHO-treated cows with the highest concentration in SUN (P ≤ 0.01). In plasma fractions, CHO was mainly found in the HLP fraction, whereas 25CHO was almost exclusively found in the protein fraction, probably due to its reported high binding affinity to vitamin D-binding protein...

  18. Gene and metabolite time-course response to cigarette smoking in mouse lung and plasma.

    Directory of Open Access Journals (Sweden)

    Mikaela A Miller

    Full Text Available Prolonged cigarette smoking (CS causes chronic obstructive pulmonary disease (COPD, a prevalent serious condition that may persist or progress after smoking cessation. To provide insight into how CS triggers COPD, we investigated temporal patterns of lung transcriptome expression and systemic metabolome changes induced by chronic CS exposure and smoking cessation. Whole lung RNA-seq data was analyzed at transcript and exon levels from C57Bl/6 mice exposed to CS for 1- or 7 days, for 3-, 6-, or 9 months, or for 6 months followed by 3 months of cessation using age-matched littermate controls. We identified previously unreported dysregulation of pyrimidine metabolism and phosphatidylinositol signaling pathways and confirmed alterations in glutathione metabolism and circadian gene pathways. Almost all dysregulated pathways demonstrated reversibility upon smoking cessation, except the lysosome pathway. Chronic CS exposure was significantly linked with alterations in pathways encoding for energy, phagocytosis, and DNA repair and triggered differential expression of genes or exons previously unreported to associate with CS or COPD, including Lox, involved in matrix remodeling, Gp2, linked to goblet cells, and Slc22a12 and Agpat3, involved in purine and glycerolipid metabolism, respectively. CS-induced lung metabolic pathways changes were validated using metabolomic profiles of matched plasma samples, indicating that dynamic metabolic gene regulation caused by CS is reflected in the plasma metabolome. Using advanced technologies, our study uncovered novel pathways and genes altered by chronic CS exposure, including those involved in pyrimidine metabolism, phosphatidylinositol signaling and lysosome function, highlighting their potential importance in the pathogenesis or diagnosis of CS-associated conditions.

  19. Associations between five-factor model of the Positive and Negative Syndrome Scale and plasma levels of monoamine metabolite in patients with schizophrenia.

    Science.gov (United States)

    Watanabe, Kenya; Miura, Itaru; Kanno-Nozaki, Keiko; Horikoshi, Sho; Mashiko, Hirobumi; Niwa, Shin-Ichi; Yabe, Hirooki

    2015-12-15

    The five-factor model of the Positive and Negative Syndrome Scale (PANSS) for schizophrenia symptoms is the most common multiple-factor model used in analyses; its use may improve evaluation of symptoms in schizophrenia patients. Plasma monoamine metabolite levels are possible indicators of clinical symptoms or response to antipsychotics in schizophrenia. We investigated the association between five-factor model components and plasma monoamine metabolites levels to explore the model's biological basis. Plasma levels of homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) were measured using high-performance liquid chromatography in 65 Japanese patients with schizophrenia. Significant negative correlation between plasma 5-HIAA levels and the depression/anxiety component was found. Furthermore, significant positive correlation was found between plasma MHPG levels and the excitement component. Plasma HVA levels were not correlated with any five-factor model component. These results suggest that the five-factor model of the PANSS may have a biological basis, and may be useful for elucidating the psychopathology of schizophrenia. Assessment using the five-factor model may enable understanding of monoaminergic dysfunction, possibly allowing more appropriate medication selection. Further studies of a larger number of first-episode schizophrenia patients are needed to confirm and extend these results. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Effect of medium-chain triglycerides on growth performance, nutrient digestibility, plasma metabolites and antioxidant capacity in weanling pigs

    Directory of Open Access Journals (Sweden)

    Yue Li

    2015-03-01

    Full Text Available The aim of this study was to investigate the effect of medium-chain triglycerides (MCTs on growth performance, nutrient digestibility, plasma metabolites and antioxidant capacity in weanling pigs. A total of 160 weanling (Duroc × Landrace × Yorkshire pigs (age: 21 ± 1 d; body weight: 7.50 ± 0.28 kg were randomly allotted to 4 treatments, receiving the following diets for 28 d: control diet [containing 3.5% soybean oil (SO], MCT1 diet (containing 0.7% MCTs and 2.8% SO, MCT2 diet (containing 1.4% MCTs and 2.1% SO and MCT3 diet (containing 2.1% MCTs and 1.4% SO. Dietary inclusion of MCTs improved the average daily gain and feed efficiency (FE of pigs compared with the control during the first 2 weeks post-weaning (P < 0.05. A similar positive effect was also observed for the overall FE in MCT2 group (P < 0.05. Compared with the control, apparent total tract digestibility (ATTD of ether extract was improved by MCT2 and MCT3 treatment from day 12–14 post-weaning (P < 0.05. In addition, MCT2 treatment also exerted a beneficial effect on the ATTD of dry matter (P < 0.05. The increased total protein concentration and decreased urea nitrogen and malondialdehyde levels of plasma were observed in both MCT2 and MCT3 groups on day 14 post-weaning (P < 0.05. In conclusion, MCTs could improve growth performance, nutrients utilization, and antioxidant ability of weanling piglets.

  1. Determination of metabolite of nicergoline in human plasma by high-performance liquid chromatography and its application in pharmacokinetic studies

    Directory of Open Access Journals (Sweden)

    Rong Zheng

    2012-02-01

    Full Text Available A fast, simple and sensitive high performance liquid chromatographic (HPLC method has been developed for determination of 10α-methoxy-6-methyl ergoline-8β-methanol (MDL, a main metabolite of nicergoline in human plasma. One-step liquid–liquid extraction (LLE with diethyl ether was employed as the sample preparation method. Tizanidine hydrochloride was selected as the internal standard (IS. Analysis was carried out on a Diamonsil ODS column (150 mm×4.6 mm, 5 μm using acetonitrile–ammonium acetate (0.1 mol/L (15/85, v/v as mobile phase at detection wavelength of 224 nm. The calibration curves were linear over the range of 2.288–73.2 ng/mL with a lower limit of quantitation (LLOQ of 2.288 ng/mL. The intra- and inter-day precision values were below 13% and the recoveries were from 74.47% to 83.20% at three quality control levels. The method herein described was successfully applied in a randomized crossover bioequivalence study of two different nicergoline preparations after administration of 30 mg in 20 healthy volunteers. Keywords: Nicergoline, 10α-methoxy-6-methylergoline-8β-methanol (MDL, HPLC, Plasma-drug concentration, Bioequivalence study

  2. Effects of Cr methionine on glucose metabolism, plasma metabolites, meat lipid peroxidation, and tissue chromium in Mahabadi goat kids.

    Science.gov (United States)

    Emami, A; Ganjkhanlou, M; Zali, A

    2015-03-01

    This study was designed to investigate the effects of chromium methionine (Cr-Met) on glucose metabolism, blood metabolites, meat lipid peroxidation, and tissue chromium (Cr) in Mahabadi goat kids. Thirty-two male kids (16.5 ± 2.8 kg BW, 4-5 months of age) were fed for 90 days in a completely randomized design with four treatments. Treatments were supplemented with 0 (control), 0.5, 1, and 1.5 mg Cr as Cr-Met/animal/daily. Blood samples were collected via heparin tubes from the jugular vein on 0, 21, 42, 63, and 90 days of experiment. On day 70, an intravenous glucose tolerance test (IVGTT) was conducted. At the end of the feeding trial, the kids were slaughtered, and the liver, kidney, and longissimus dorsi (LD) muscle samples were collected. Plasma glucose, insulin, and triglyceride concentrations were decreased by Cr supplementation (P glucose concentrations at 30 and 60 min after glucose infusion were lower in the kids fed 1.5 mg Cr diet than the kids fed control diet (P glucose clearance rate (K) and lower glucose half-life (T½; P Glucose area under the response curve (AUC) from 0 to 180 min after glucose infusion was decreased linearly (P glucose utilization and lipid oxidation of meat in fattening kid.

  3. Direct speciation analysis of arsenic in whole blood and blood plasma at low exposure levels by hydride generation-cryotrapping-inductively coupled plasma mass spectrometry

    Czech Academy of Sciences Publication Activity Database

    Matoušek, Tomáš; Wang, Z.; Douillet, Ch.; Musil, Stanislav; Stýblo, M.

    2017-01-01

    Roč. 89, č. 18 (2017), s. 9633-9637 ISSN 0003-2700 R&D Projects: GA MŠk(CZ) LH15174 Institutional support: RVO:68081715 Keywords : speciation analysis * arsenic * blood Subject RIV: CB - Analytical Chemistry , Separation OBOR OECD: Analytical chemistry Impact factor: 6.320, year: 2016

  4. Direct speciation analysis of arsenic in whole blood and blood plasma at low exposure levels by hydride generation-cryotrapping-inductively coupled plasma mass spectrometry

    Czech Academy of Sciences Publication Activity Database

    Matoušek, Tomáš; Wang, Z.; Douillet, Ch.; Musil, Stanislav; Stýblo, M.

    2017-01-01

    Roč. 89, č. 18 (2017), s. 9633-9637 ISSN 0003-2700 R&D Projects: GA MŠk(CZ) LH15174 Institutional support: RVO:68081715 Keywords : speciation analysis * arsenic * blood Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 6.320, year: 2016

  5. High-performance liquid chromatographic determination of certain salicylates and their major metabolites in plasma following topical administration of a liniment to healthy subjects.

    Science.gov (United States)

    Dadgar, D; Climax, J; Lambe, R; Darragh, A

    1985-08-09

    The liniment used is a topical analgesic and anti-inflammatory preparation containing two active constituents, 3-phenylpropylsalicylate and ethyl-5-methoxysalicylate, in solution in isobutyl decanoate. It is known that 3-phenylpropylsalicylate is metabolised to salicylic acid and salicyluric acid and ethyl-5-methoxysalicylate is metabolised to 5-methoxysalicylic acid and gentisic acid. In the present study the separation of the salicylates and their metabolites was carried out on a Waters mu Bondapak C18 column using two different mobile phases, methanol-water (80:20) for the parent drugs and methanol-5% aqueous acetic acid (27:73) for their metabolites. The salicylates and their metabolites were detected by absorption at 310 nm. The limits of detection for parent drugs and metabolites were respectively 0.2 and 0.1 microgram/ml in plasma, using a 1-ml plasma sample and a 20-microliter injection from a reconstituted volume of 250 microliter. Mean percentage coefficients of variation for intra-assay and inter-assay precision were between 3.3 +/- 1.9% to 9.1 +/- 3.7% and 6.8 +/- 2.2% to 15.7 +/- 10.1%, respectively. Linearity, as measured by the correlation coefficient of intra-assay linear regression curves, was better than 0.998 in all cases.

  6. Production performance and plasma metabolites of dairy ewes in early lactation as affected by chitosan

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Rodriguez, A.; Arranz, J.; Mandaluniz, N.; Beltrán-de-Heredia, I.; Ruiz, R.; Goiri, I.

    2015-07-01

    The objective of this study was to evaluate the effects of chitosan (CHI) supplementation on production performance and blood parameters in dairy ewes. Twenty-four multiparous Latxa dairy ewes at d 16 of lactation were divided into two groups of 12 ewes each. Ewes were fed one of two experimental concentrates (0.840 kg dry matter/d), control or supplemented with 1.2% CHI, on a dry matter basis. Ewes also had free access to tall fescue hay, water, and mineral salts. The experimental period lasted for 25 d, of which the first 14 d were for treatment adaptation and the last 11 d for measurements and samplings. Supplementation with CHI decreased total (p=0.043) and fescue (p=0.035) dry matter intake (DMI), but did not affect concentrate DMI. Supplementation with CHI, moreover, increased plasma glucose (p=0.013) and BUN concentrations (p=0.035), but did not affect those of non-esterified fatty acids. Dietary supplementation with CHI, however, did not affect milk yield, 6.5% FCM, milk composition, or BW, but it improved dietary apparent efficiency by increasing the milk yield-to-DMI (p=0.055) and 6.5% FCM-to-DMI (p=0.045) ratios. In conclusion, dietary supplementation of chitosan maintained ewe performance while reducing feed intake and improving dietary apparent efficiency. (Author)

  7. Arsenic transport by zebrafish aquaglyceroporins

    Directory of Open Access Journals (Sweden)

    Landfear Scott M

    2009-11-01

    Full Text Available Abstract Background Arsenic is one of the most ubiquitous toxins and endangers the health of tens of millions of humans worldwide. It is a mainly a water-borne contaminant. Inorganic trivalent arsenic (AsIII is one of the major species that exists environmentally. The transport of AsIII has been studied in microbes, plants and mammals. Members of the aquaglyceroporin family have been shown to actively conduct AsIII and its organic metabolite, monomethylarsenite (MAsIII. However, the transport of AsIII and MAsIII in in any fish species has not been characterized. Results In this study, five members of the aquaglyceroporin family from zebrafish (Danio rerio were cloned, and their ability to transport water, glycerol, and trivalent arsenicals (AsIII and MAsIII and antimonite (SbIII was investigated. Genes for at least seven aquaglyceroporins have been annotated in the zebrafish genome project. Here, five genes which are close homologues to human AQP3, AQP9 and AQP10 were cloned from a zebrafish cDNA preparation. These genes were named aqp3, aqp3l, aqp9a, aqp9b and aqp10 according to their similarities to the corresponding human AQPs. Expression of aqp9a, aqp9b, aqp3, aqp3l and aqp10 in multiple zebrafish organs were examined by RT-PCR. Our results demonstrated that these aquaglyceroporins exhibited different tissue expression. They are all detected in more than one tissue. The ability of these five aquaglyceroporins to transport water, glycerol and the metalloids arsenic and antimony was examined following expression in oocytes from Xenopus leavis. Each of these channels showed substantial glycerol transport at equivalent rates. These aquaglyceroporins also facilitate uptake of inorganic AsIII, MAsIII and SbIII. Arsenic accumulation in fish larvae and in different tissues from adult zebrafish was studied following short-term arsenic exposure. The results showed that liver is the major organ of arsenic accumulation; other tissues such as gill, eye

  8. Arsenic (+3 oxidation state) methyltransferase and the inorganic arsenic methylation phenotype

    International Nuclear Information System (INIS)

    Li Jiaxin; Waters, Stephen B.; Drobna, Zuzana; Devesa, Vicenta; Styblo, Miroslav; Thomas, David J.

    2005-01-01

    Inorganic arsenic is enzymatically methylated; hence, its ingestion results in exposure to the parent compound and various methylated arsenicals. Both experimental and epidemiological evidences suggest that some of the adverse health effects associated with chronic exposure to inorganic arsenic may be mediated by these methylated metabolites. If i As methylation is an activation process, then the phenotype for inorganic arsenic methylation may determine risk associated with exposure to this metalloid. We examined inorganic arsenic methylation phenotypes and arsenic (+3 oxidation state) methyltransferase genotypes in four species: three that methylate inorganic arsenic (human (Homo sapiens), rat (Rattus norwegicus), and mouse (Mus musculus)) and one that does not methylate inorganic arsenic (chimpanzee, Pan troglodytes). The predicted protein products from arsenic (+3 oxidation state) methyltransferase are similar in size for rat (369 amino acid residues), mouse (376 residues), and human (375 residues). By comparison, a 275-nucleotide deletion beginning at nucleotide 612 in the chimpanzee gene sequence causes a frameshift that leads to a nonsense mutation for a premature stop codon after amino acid 205. The null phenotype for inorganic arsenic methylation in the chimpanzee is likely due to the deletion in the gene for arsenic (+3 oxidation state) methyltransferase that yields an inactive truncated protein. This lineage-specific loss of function caused by the deletion event must have occurred in the Pan lineage after Homo-Pan divergence about 5 million years ago

  9. Factors Affecting Arsenic Methylation in Arsenic-Exposed Humans: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Shen, Hui; Niu, Qiang; Xu, Mengchuan; Rui, Dongsheng; Xu, Shangzhi; Feng, Gangling; Ding, Yusong; Li, Shugang; Jing, Mingxia

    2016-02-06

    Chronic arsenic exposure is a critical public health issue in many countries. The metabolism of arsenic in vivo is complicated because it can be influenced by many factors. In the present meta-analysis, two researchers independently searched electronic databases, including the Cochrane Library, PubMed, Springer, Embase, and China National Knowledge Infrastructure, to analyze factors influencing arsenic methylation. The concentrations of the following arsenic metabolites increase (piAs), monomethyl arsenic (MMA), dimethyl arsenic (DMA), and total arsenic. Additionally, the percentages of iAs (standard mean difference (SMD): 1.00; 95% confidence interval (CI): 0.60-1.40; p< 0.00001) and MMA (SMD: 0.49; 95% CI: 0.21-0.77; p = 0.0006) also increase, while the percentage of DMA (SMD: -0.57; 95% CI: -0.80--0.31; p< 0.0001), primary methylation index (SMD: -0.57; 95% CI: -0.94--0.20; p = 0.002), and secondary methylation index (SMD: -0.27; 95% CI: -0.46--0.90; p = 0.004) decrease. Smoking, drinking, and older age can reduce arsenic methylation, and arsenic methylation is more efficient in women than in men. The results of this analysis may provide information regarding the role of arsenic oxidative methylation in the arsenic poisoning process.

  10. Dietary Arsenic Exposure in Bangladesh

    OpenAIRE

    Kile, Molly L.; Houseman, E. Andres; Breton, Carrie V.; Smith, Thomas; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Christiani, David C.

    2007-01-01

    Background Millions of people in Bangladesh are at risk of chronic arsenic toxicity from drinking contaminated groundwater, but little is known about diet as an additional source of As exposure. Methods We employed a duplicate diet survey to quantify daily As intake in 47 women residing in Pabna, Bangladesh. All samples were analyzed for total As, and a subset of 35 samples were measured for inorganic arsenic (iAs) using inductively coupled plasma mass spectrometry equipped with a dynamic rea...

  11. T05 DETERMINATION OF REDUCED ARSENIC-THIO SPECIES IN WATERS BY ION CHROMATOGRAPHY-INDUCTIVELY-COUPLED PLASMA-MASS SSPECTROMETRY (IC-ICP-MS).

    Science.gov (United States)

    Elevated arsenic concentrations in ground water are a significant concern for human health, because they may lead to increased arsenic exposure via drinking water. As the inorganic arsenic species arsenite (As(III)) and arsenate (As(V)) are known carcinogens, it is desirable to r...

  12. Determination of oxycodone and its major metabolites noroxycodone and oxymorphone by ultra-high-performance liquid chromatography tandem mass spectrometry in plasma and urine: application to real cases.

    Science.gov (United States)

    Pantano, Flaminia; Brauneis, Stefano; Forneris, Alexandre; Pacifici, Roberta; Marinelli, Enrico; Kyriakou, Chrystalla; Pichini, Simona; Busardò, Francesco Paolo

    2017-08-28

    Oxycodone is a narcotic drug widely used to alleviate moderate and severe acute and chronic pain. Variability in analgesic efficacy could be explained by inter-subject variations in plasma concentrations of parent drug and its active metabolite, oxymorphone. To evaluate patient compliance and to set up therapeutic drug monitoring (TDM), an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) assay was developed and validated for the parent drug and its major metabolites noroxycodone and oxymorphone. Extraction of analytes from plasma and urine samples was obtained by simple liquid-liquid extraction. The chromatographic separation was achieved with a reversed phase column using a linear gradient elution with two solvents: acetic acid 1% in water and methanol. The separated analytes were detected with a triple quadrupole mass spectrometer operated in multiple reaction monitoring (MRM) mode via positive electrospray ionization (ESI). Separation of analytes was obtained in less than 5 min. Linear calibration curves for all the analytes under investigation in urine and plasma samples showed determination coefficients (r2) equal or higher than 0.990. Mean absolute analytical recoveries were always above 86%. Intra- and inter-assay precision (measured as coefficient of variation, CV%) and accuracy (measured as % error) values were always better than 13%. Limit of detection at 0.06 and 0.15 ng/mL and limit of quantification at 0.2 and 0.5 ng/mL for plasma and urine samples, respectively, were adequate for the purpose of the present study. Rapid extraction, identification and quantification of oxycodone and its metabolites both in urine and plasma by UHPLC-MS/MS assay was tested for its feasibility in clinical samples and provided excellent results for rapid and effective drug testing in patients under oxycodone treatment.

  13. Simultaneous densitometric determination of anthelmintic drug albendazole and its metabolite albendazole sulfoxide by HPTLC in human plasma and pharmaceutical formulations.

    Science.gov (United States)

    Pandya, Jui J; Sanyal, Mallika; Shrivastav, Pranav S

    2017-09-01

    A new, simple, accurate and precise high-performance thin-layer chromatographic method has been developed and validated for simultaneous determination of an anthelmintic drug, albendazole, and its active metabolite albendazole, sulfoxide. Planar chromatographic separation was performed on aluminum-backed layer of silica gel 60G F 254 using a mixture of toluene-acetonitrile-glacial acetic acid (7.0:2.9:0.1, v/v/v) as the mobile phase. For quantitation, the separated spots were scanned densitometrically at 225 nm. The retention factors (R f ) obtained under the established conditions were 0.76 ± 0.01 and 0.50 ± 0.01 and the regression plots were linear (r 2  ≥ 0.9997) in the concentration ranges 50-350 and 100-700 ng/band for albendazole and albendazole sulfoxide, respectively. The method was validated for linearity, specificity, accuracy (recovery) and precision, repeatability, stability and robustness. The limit of detection and limit of quantitation found were 9.84 and 29.81 ng/band for albendazole and 21.60 and 65.45 ng/band for albendazole sulfoxide, respectively. For plasma samples, solid-phase extraction of analytes yielded mean extraction recoveries of 87.59 and 87.13% for albendazole and albendazole sulfoxide, respectively. The method was successfully applied for the analysis of albendazole in pharmaceutical formulations with accuracy ≥99.32%. Copyright © 2017 John Wiley & Sons, Ltd.

  14. Arsenic speciation in seafood samples with emphasis on minor constituents. An investigation by high performance liquid chromatography with inductively coupled plasma mass spectrometric detection

    DEFF Research Database (Denmark)

    Larsen, Erik Huusfeldt; Pritzl, G.; Hansen, S. H.

    1993-01-01

    Extracts of 11 samples of shrimp, crab, fish, fish liver, shellfish and lobster digestive gland (hepatopancreas), including five certified reference materials, were investigated for their contents of arsenic compounds (arsenic speciation). The cation-exchange high performance liquid chromatography...... (as arsenic atom) relative to the total arsenic extracted from the samples were: arsenobetaine 19-98%, arsenocholine and trimethylarsine oxide 0-0.6% and the trimethylarsonium ion 0-2.2%. Additionally, an unknown arsenic species (U1) was present at 3.1-18% in the shellfish and in the lobster digestive...

  15. IDENTIFICATION OF INTERSPECIES CONCORDANCE OF MECHANISMS OF ARSENIC INDUCED BLADDER CANCER BY GENE EXPRESSION.

    Science.gov (United States)

    Arsenic is a human carcinogen that induces urinary bladder cancer. Several mechanisms have been proposed for arsenic-induced cancer. Although inorganic arsenic (iAs) does not induce tumors in adult rodents, dimethylarsinic acid (DMA), a major metabolite of iAs, is a rat bladder c...

  16. Oral Administration of the Japanese Traditional Medicine Keishibukuryogan-ka-yokuinin Decreases Reactive Oxygen Metabolites in Rat Plasma: Identification of Chemical Constituents Contributing to Antioxidant Activity

    Directory of Open Access Journals (Sweden)

    Yosuke Matsubara

    2017-02-01

    Full Text Available Insufficient detoxification and/or overproduction of reactive oxygen species (ROS induce cellular and tissue damage, and generated reactive oxygen metabolites become exacerbating factors of dermatitis. Keishibukuryogan-ka-yokuinin (KBGY is a traditional Japanese medicine prescribed to treat dermatitis such as acne vulgaris. Our aim was to verify the antioxidant properties of KBGY, and identify its active constituents by blood pharmacokinetic techniques. Chemical constituents were quantified in extracts of KBGY, crude components, and the plasma of rats treated with a single oral administration of KBGY. Twenty-three KBGY compounds were detected in plasma, including gallic acid, prunasin, paeoniflorin, and azelaic acid, which have been reported to be effective for inflammation. KBGY decreased level of the diacron-reactive oxygen metabolites (d-ROMs in plasma. ROS-scavenging and lipid hydroperoxide (LPO generation assays revealed that gallic acid, 3-O-methylgallic acid, (+-catechin, and lariciresinol possess strong antioxidant activities. Gallic acid was active at a similar concentration to the maximum plasma concentration, therefore, our findings indicate that gallic acid is an important active constituent contributing to the antioxidant effects of KBGY. KBGY and its active constituents may improve redox imbalances induced by oxidative stress as an optional treatment for skin diseases.

  17. Simultaneous determination of clebopride and a major metabolite N-desbenzylclebopride in plasma by capillary gas chromatography-negative-ion chemical ionization mass spectrometry.

    Science.gov (United States)

    Robinson, P R; Jones, M D; Maddock, J; Rees, L W

    1991-03-08

    A procedure for the simultaneous assay of clebopride and its major metabolite N-desbenzylclebopride in plasma has been developed. The method utilizes capillary gas chromatography-negative-ion chemical ionization mass spectrometry with selected-ion monitoring of characteristic ions. Employing 2-ethoxy analogues as internal standards, the benzamides were extracted from basified plasma using dichloromethane. Subsequent reaction with heptafluorobutyric anhydride produced volatile mono- and diheptafluorobutyryl derivatives of clebopride and N-desbenzylclebopride, respectively. The methane negative-ion mass spectra of these derivatives exhibited intense high-mass ions ideal for specific quantitation of low levels in biological fluids. Using this procedure the recovery of the drug and metabolite from human plasma was found to be 84.4 +/- 1.5% (n = 3) and 77.4 +/- 4.7% (n = 3), respectively, at 0.5 ng/ml. Measurement of both compounds down to 0.10 ng/ml with a coefficient of variation of less than 10.5% is described. Plasma levels are reported in four volunteers up to 24 h following oral administration of 1 mg of clebopride malate salt.

  18. Simultaneous determination of sibutramine and its active metabolites in human plasma by LC-MS/MS and its application to a pharmacokinetic study.

    Science.gov (United States)

    Bae, Jung-Woo; Choi, Chang-Ik; Jang, Choon-Gon; Lee, Seok-Yong

    2011-11-01

    A simple and sensitive liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) technique was developed and validated for the determination of sibutramine and its N-desmethyl metabolites (M1 and M2) in human plasma. After extraction with methyl t-butyl ether, chromatographic separation of analytes in human plasma was performed using a reverse-phase Luna C18 column with a mobile phase of acetonitrile-10 mm ammonium formate buffer (50:50, v/v) and quantified by ESI-MS/MS detection in positive ion mode. The flow rate of the mobile phase was 200 μL/min and the retention times of sibutramine, M1, M2 and internal standard (chlorpheniramine) were 1.5, 1.4, 1.3 and 0.9 min, respectively. The calibration curves were linear over the range 0.05-20 ng/mL, for sibutramine, M1 and M2. The lower limit of quantification was 0.05 ng/mL using 500 μL of human plasma. The mean accuracy and the precision in the intra- and inter-day validation for sibutramine, M1 and M2 were acceptable. This LC-MS/MS method showed improved sensitivity and a short run time for the quantification of sibutramine and its two active metabolites in plasma. The validated method was successfully applied to a pharmacokinetic study in human. Copyright © 2011 John Wiley & Sons, Ltd.

  19. The plasma and cerebrospinal fluid pharmacokinetics of erlotinib and its active metabolite (OSI-420) after intravenous administration of erlotinib in non-human primates.

    Science.gov (United States)

    Meany, Holly J; Fox, Elizabeth; McCully, Cynthia; Tucker, Chris; Balis, Frank M

    2008-08-01

    Erlotinib hydrochloride is a small molecule inhibitor of epidermal growth factor receptor (EGFR). EGFR is over-expressed in primary brain tumors and solid tumors that metastasize to the central nervous system. We evaluated the plasma and cerebrospinal fluid (CSF) pharmacokinetics of erlotinib and its active metabolite OSI-420 after an intravenous (IV) dose in a non-human primate model. Erlotinib was administered as a 1 h IV infusion to four adult rhesus monkeys. Serial blood and CSF samples were drawn over 48 h and erlotinib and OSI-420 were quantified with an HPLC/tandem mass spectroscopic assay. Pharmacokinetic parameters were estimated using non-compartmental and compartmental methods. CSF penetration was calculated from the AUC(CSF):AUC(plasma). Erlotinib disappearance from plasma after a short IV infusion was biexponential with a mean terminal half-life of 5.2 h and a mean clearance of 128 ml/min per m(2). OSI-420 exposure (AUC) in plasma was 30% (range 12-59%) of erlotinib, and OSI-420 clearance was more than 5-fold higher than erlotinib. Erlotinib and OSI-420 were detectable in CSF. The CSF penetration (AUC(CSF):AUC(plasma)) of erlotinib and OSI-420 was OSI-420 are measurable in CSF after an IV dose. The drug exposure (AUC) in the CSF is limited relative to total plasma concentrations but is substantial relative the free drug exposure in plasma.

  20. The metabolites in peripheral blood mononuclear cells showed greater differences between patients with impaired fasting glucose or type 2 diabetes and healthy controls than those in plasma.

    Science.gov (United States)

    Kim, Minjoo; Kim, Minkyung; Han, Ji Yun; Lee, Sang-Hyun; Jee, Sun Ha; Lee, Jong Ho

    2017-03-01

    To determine differences between peripheral blood mononuclear cells and the plasma metabolites in patients with impaired fasting glucose or type 2 diabetes and healthy controls. In all, 65 nononobese patients (aged 30-70 years) with impaired fasting glucose or type 2 diabetes and 65 nonobese sex-matched healthy controls were included, and fasting peripheral blood mononuclear cell and plasma metabolomes were profiled. The diabetic or impaired fasting glucose patients showed higher circulating and peripheral blood mononuclear cell lipoprotein phospholipase A 2 activities, high-sensitivity C-reactive protein and tumour necrosis factor-α than controls. Compared with controls, impaired fasting glucose or diabetic subjects showed increases in 11 peripheral blood mononuclear cell metabolites: six amino acids (valine, leucine, methionine, phenylalanine, tyrosine and tryptophan), l-pyroglutamic acid, two fatty acid amides containing palmitic amide and oleamide and two lysophosphatidylcholines. In impaired fasting glucose or diabetic patients, peripheral blood mononuclear cell lipoprotein phospholipase A 2 positively associated with peripheral blood mononuclear cell lysophosphatidylcholines and circulating inflammatory markers, including tumour necrosis factor-α, high-sensitivity C-reactive protein and lipoprotein phospholipase A 2 activities. In plasma metabolites between patients and healthy controls, we observed significant increases in only three amino acids (proline, valine and leucine) and decreases in only five lysophosphatidylcholines. This study demonstrates significant differences in the peripheral blood mononuclear cell metabolome in patients with impaired fasting glucose or diabetes compared with healthy controls. These differences were greater than those observed in the plasma metabolome. These data suggest peripheral blood mononuclear cells as a useful tool to better understand the inflammatory pathophysiology of diabetes.

  1. Certification of total arsenic in blood and urine standard reference materials by radiochemical neutron activation analysis and inductively coupled plasma-mass spectrometry

    International Nuclear Information System (INIS)

    Paul, R.L.; Clay Davis, W.; Lee Yu; Murphy, K.E.; Bryan, C.E.; Vetter, T.W.; Guthrie, W.F.; Leber, D.D.; Gulchekhra Shakirova; Graylin Mitchell

    2014-01-01

    Radiochemical neutron activation analysis (RNAA) was used to measure arsenic at four levels in standard reference material (SRM) 955c Toxic Elements in Caprine Blood and at two levels in SRM 2668 Toxic Elements in Frozen Human Urine for the purpose of providing mass concentration values for certification. Samples were freeze-dried prior to analysis followed by neutron irradiation for 3 h at a fluence rate of 1 × 10 14 cm -2 s -1 . After sample dissolution in perchloric and nitric acids, arsenic was separated from the matrix either by retention on hydrated manganese dioxide (urine) or by extraction into zinc diethyldithiocarbamate in chloroform (blood). 76 As was quantified by gamma-ray spectroscopy. Differences in chemical yield and counting geometry between samples and standards were monitored by measuring the count rate of a 77 As tracer added before sample dissolution. RNAA results were combined with inductively coupled plasma-mass spectrometry values from National Institute of Standards and Technology and collaborating laboratories to provide certified values of 10.81 ± 0.54 and 213.1 ± 0.73 μg/L for SRM 2668 Levels I and II, and certified values of 21.66 ± 0.73, 52.7 ± 1.1, and 78.8 ± 4.9 μg/L for SRM 955c Levels II-IV, respectively. Because of discrepancies between values obtained by different methods for SRM 955c Level I, an information value of <5 μg/L was assigned for this material. (author)

  2. Effects of vitamin D3 supplementation and UVb exposure on the growth and plasma concentration of vitamin D3 metabolites in juvenile bearded dragons (Pogona vitticeps).

    Science.gov (United States)

    Oonincx, D G A B; Stevens, Y; van den Borne, J J G C; van Leeuwen, J P T M; Hendriks, W H

    2010-06-01

    The effectiveness of dietary vitamin D3 and UVb exposure on plasma vitamin D metabolites in growing bearded dragons (Pogona vitticeps) was studied. A total of 84 (40 males and 44 females) newly hatched bearded dragons were allocated to six levels of oral vitamin D3 supplementation (0 to 400%) or six UVb exposure times (2 to 12 h). At 3 and 6 months of age, blood samples were obtained from each animal and analysed for 25(OH)D3 and 1,25(OH)2D3. At 3 months of age, plasma concentrations of 25(OH)D3 did not increase with increasing vitamin D3 supplementation unlike the 1,25(OH)2D3. At 6 months of age, plasma concentrations of both 25(OH)D(3) and 1,25(OH)2D3 increased with increasing vitamin D(3) supplementation. Plasma concentrations in UVb-exposed animals were 18 times higher for 25(OH)D3 (178.4+/-9.0 vs. 9.9+/-1.3 nmol/L) and 5.3 times higher for 1,25(OH)2D3 (1.205+/-0.100 vs. 0.229+/-0.025 nmol/L) than in vitamin D(3) supplemented animals at 6 months of age. This study shows that 2h of UVb exposure enables adequate physiological concentrations of plasma vitamin D metabolites to be maintained in growing bearded dragons. Oral supplementation of vitamin D(3) is ineffective in raising plasma concentrations of 25(OH)D3 and 1,25(OH)2D3 to concentrations observed in UVb-exposed animals. 2010 Elsevier Inc. All rights reserved.

  3. Usefulness of saliva for measurement of 3,4-methylenedioxymethamphetamine and its metabolites: correlation with plasma drug concentrations and effect of salivary pH.

    Science.gov (United States)

    Navarro, M; Pichini, S; Farré, M; Ortuño, J; Roset, P N; Segura, J; de la Torre, R

    2001-10-01

    Saliva is an alternative biologic matrix for drugs-of-abuse testing that offers the advantages of noninvasive, rapid, and easy sampling. We studied the excretion profile of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolites in both saliva and plasma, as well the effect of the drug on salivary pH. Saliva and plasma samples were obtained from eight healthy MDMA consumers after ingestion of a single 100-mg dose of the drug. Concentrations of MDMA and its main metabolites, 3,4-methylenedioxyamphetamine (MDA) and 4-hydroxy-3-methoxymethamphetamine (HMMA), in saliva and plasma were measured by gas chromatography-mass spectrometry. Apparent pharmacokinetic parameters for MDMA in saliva were estimated, and the saliva-to-plasma ratio at each time interval was calculated and correlated with salivary pH. MDMA, MDA, and HMMA were detected in saliva. Salivary concentrations of MDMA were 1728.9-6510.6 microg/L and peaked at 1.5 h after drug intake. This was followed by a progressive decrease, with a mean concentration of 126.2 microg/L at 24 h. The saliva-to-plasma ratio was 32.3-1.2, with a peak of 18.1 at 1.5 h after drug administration. Salivary pH seemed to be affected by MDMA administration; pH values decreased by 0.6 units (mean pH values of 6.9 and 6.8 at 1.5 and 4 h after drug administration vs predose pH of 7.4). Measurement of MDMA in saliva is a valuable alternative to determination of plasma drug concentrations in both clinical and toxicologic studies. On-site testing is also facilitated by noninvasive and rapid collection of salivary specimens.

  4. Creatinine, diet, micronutrients, and arsenic methylation in West Bengal, India.

    Science.gov (United States)

    Basu, Arin; Mitra, Soma; Chung, Joyce; Guha Mazumder, D N; Ghosh, Nilima; Kalman, David; von Ehrenstein, Ondine S; Steinmaus, Craig; Liaw, Jane; Smith, Allan H

    2011-09-01

    Ingested inorganic arsenic (InAs) is methylated to monomethylated (MMA) and dimethylated metabolites (DMA). Methylation may have an important role in arsenic toxicity, because the monomethylated trivalent metabolite [MMA(III)] is highly toxic. We assessed the relationship of creatinine and nutrition--using dietary intake and blood concentrations of micronutrients--with arsenic metabolism, as reflected in the proportions of InAS, MMA, and DMA in urine, in the first study that incorporated both dietary and micronutrient data. We studied methylation patterns and nutritional factors in 405 persons who were selected from a cross-sectional survey of 7,638 people in an arsenic-exposed population in West Bengal, India. We assessed associations of urine creatinine and nutritional factors (19 dietary intake variables and 16 blood micronutrients) with arsenic metabolites in urine. Urinary creatinine had the strongest relationship with overall arsenic methylation to DMA. Those with the highest urinary creatinine concentrations had 7.2% more arsenic as DMA compared with those with low creatinine (p creatinine concentration was the strongest biological marker of arsenic methylation efficiency, and therefore should not be used to adjust for urine concentration in arsenic studies. The new finding that animal fat intake has a positive relationship with MMA% warrants further assessment in other studies. Increased MMA% was also associated, to a lesser extent, with low serum selenium and folate.

  5. Urinary arsenic profiles reveal exposures to inorganic arsenic from private drinking water supplies in Cornwall, UK

    Science.gov (United States)

    Middleton, D. R. S.; Watts, M. J.; Hamilton, E. M.; Ander, E. L.; Close, R. M.; Exley, K. S.; Crabbe, H.; Leonardi, G. S.; Fletcher, T.; Polya, D. A.

    2016-05-01

    Private water supplies (PWS) in Cornwall, South West England exceeded the current WHO guidance value and UK prescribed concentration or value (PCV) for arsenic of 10 μg/L in 5% of properties surveyed (n = 497). In this follow-up study, the first of its kind in the UK, volunteers (n = 207) from 127 households who used their PWS for drinking, provided urine and drinking water samples for total As determination by inductively coupled plasma mass spectrometry (ICP-MS) and urinary As speciation by high performance liquid chromatography ICP-MS (HPLC-ICP-MS). Arsenic concentrations exceeding 10 μg/L were found in the PWS of 10% of the volunteers. Unadjusted total urinary As concentrations were poorly correlated (Spearman’s ρ = 0.36 (P < 0.001)) with PWS As largely due to the use of spot urine samples and the dominance of arsenobetaine (AB) from seafood sources. However, the osmolality adjusted sum, U-AsIMM, of urinary inorganic As species, arsenite (AsIII) and arsenate (AsV), and their metabolites, methylarsonate (MA) and dimethylarsinate (DMA), was found to strongly correlate (Spearman’s ρ: 0.62 (P < 0.001)) with PWS As, indicating private water supplies as the dominant source of inorganic As exposure in the study population of PWS users.

  6. In matrix derivatization of trichloroethylene metabolites in human plasma with methyl chloroformate and their determination by solid-phase microextraction-gas chromatography-electron capture detector.

    Science.gov (United States)

    Mudiam, Mohana Krishna Reddy; Jain, Rajeev; Varshney, Meenu; Ch, Ratnasekhar; Chauhan, Abhishek; Goyal, Sudhir Kumar; Khan, Haider A; Murthy, R C

    2013-04-15

    Trichloroethylene (TCE) is a common industrial chemical that has been widely used as metal degreaser and for many industrial purposes. In humans, TCE is metabolized into dichloroacetic acid (DCA), trichloroacetic acid (TCA) and trichloroethanol (TCOH). A simple and rapid method has been developed for the quantitative determination of TCE metabolites. The procedure involves the in situ derivatization of TCE metabolites with methyl chloroformate (MCF) directly in diluted plasma samples followed by extraction and analysis with solid-phase microextraction (SPME) coupled to gas chromatography-electron capture detector (GC-ECD). Factors which can influence the efficiency of derivatization such as amount of MCF and pyridine (PYR), ratio of water/methanol were optimized. The factors which can affect the extraction efficiencies of SPME were screened using 2(7-4) Placket-Burman Design (PBD). A central composite design (CCD) was then applied to further optimize the most significant factors for optimum SPME extraction. The optimum factors for the SPME extraction were found to be 562.5mg of NaCl, pH at 1 and an extraction time of 22 min. Recoveries and detection limits of all three analytes in plasma were found to be in the range of 92.69-97.55% and 0.036-0.068 μg mL(-1) of plasma, respectively. The correlation coefficients were found to be in the range of 0.990-0.995. The intra- and inter-day precisions for TCE metabolites were found to be in the range of 2.37-4.81% and 5.13-7.61%, respectively. The major advantage of this method is that MCF derivatization allows conversion of TCE metabolites into their methyl esters in very short time (≤30 s) at room temperature directly in the plasma samples, thus makes it a solventless analysis. The method developed was successfully applied to the plasma samples of humans exposed to TCE. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Corticosterone stress response and plasma metabolite levels during breeding and molt in a free-living migratory songbird, the wood thrush (Hylocichla mustelina).

    Science.gov (United States)

    Done, Tyler; Gow, Elizabeth A; Stutchbury, Bridget J M

    2011-04-01

    Many birds face energetic trade-offs between different life history stages, such as reproductive effort, feather molt and the non-breeding period. Little is known about how physiological measures of condition (corticosterone, plasma metabolites) in free-living birds change from nesting stages to the post-breeding molt period or whether this is influenced by prior reproductive effort. We evaluated whether corticosterone (CORT) and plasma metabolite levels vary with date, nest stage and sex in a free-living migratory songbird, the wood thrush (Hylocichla mustelina). We also tested whether (1) baseline CORT levels early in the season were predictive of subsequent reproductive success and (2) whether prior reproductive effort influenced CORT levels and blood metabolites during molt. Baseline CORT levels decreased with date during both the incubation stage and nestling stage, but did not vary significantly across stage of breeding season. Stress-induced CORT declined with date during incubation and varied significantly across breeding stage, with lower levels during feather molt. Profiles of the metabolites of β-hydroxybutyrate, glycerol, and triglyceride did not vary significantly with date or breeding stage. Only triglycerides varied significantly with sex, with females having higher levels than males. Reproductive output was highly variable (0-10 fledglings per season) but baseline CORT levels in females during the first incubation period of the season was not related to subsequent reproductive output. Prior reproductive effort, measured as the cumulative number of young hatched during the breeding season, was positively related to stress-induced CORT during molt. High reproductive effort in wood thrush appears to have physiological carry-over effects into the molt period which could potentially affect rate of molt and preparation for fall migration. Copyright © 2011. Published by Elsevier Inc.

  8. Inhibition by methylated organo-arsenicals of the respiratory 2-oxo-acid dehydrogenases

    OpenAIRE

    Bergquist, Erik R.; Fischer, Robert J.; Sugden, Kent D.; Martin, Brooke D

    2009-01-01

    Inorganic arsenic that is ingested through drinking water or inhalation is metabolized by biological methylation pathways into organoarsenical metabolites. It is now becoming understood that this metabolism that was formerly considered to be detoxification may contribute as much or more to increasing the toxicity of arsenic. One proposed mode of the toxic action of arsenic and its organoarsenic metabolites is through its binding to proteins and inactivating their enzymatic activity. The class...

  9. Quantitation of anacetrapib, stable-isotope labeled-anacetrapib (microdose), and four metabolites in human plasma using liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Chavez-Eng, C M; Lutz, R W; Li, H; Goykhman, D; Bateman, K P; Woolf, E

    2016-02-01

    An ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of (4S,5R)-5-[3,5-bis (trifluoromethyl)phenyl]-3-{[4'-fluoro-5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl] methyl}-4-methyl-1,3-oxazolidin-2-one (anacetrapib, I) and [(13)C5(15)N]-anacetrapib, II in human plasma has been developed to support a clinical study to determine the absolute bioavailability of I. The analytes and the stable-isotope labeled internal standard ([(13)C7(15)N(2)H7]-anacetrapib, III) were extracted from 100μL of human plasma by liquid-liquid extraction using 20/80 isopropyl alcohol/hexane (v/v). The chromatographic separation of the analytes was achieved using Waters BEH Shield RP 18 (50×2.1mm×1.7μm) column and mobile phase gradient of 0.1% formic acid in water (Solvent A) and 0.1% formic acid in acetonitrile (Solvent B) at 0.6mL/min flow rate. The MS/MS detection was performed on AB Sciex 5000 or AB 5500 in positive electrospray ionization mode, operated in selected reaction monitoring mode. The assay was validated in the concentration range 1-2000ng/mL for I; and a lower curve range, 0.025-50ng/mL for II. In addition to the absolute bioavailability determination, it was desired to better elucidate the pharmacokinetic behavior of several hydroxylated metabolites of I. Toward this end, two exploratory assays for the hydroxy metabolites of I were qualified in the concentration range 0.5-500ng/mL. All metabolites were separated on a Supelco Ascentis Express Phenyl-Hexyl (50×2.1mm, 2.7μm) column. Metabolite M4 was analyzed in the negative mode with a mobile phase consisting of a gradient mixture of water (A) and acetonitrile (B). The other three metabolites, M1-M3 were analyzed in the positive mode using a mobile phase gradient of water with 0.1% formic acid (A) and acetonitrile with 0.1% formic acid (B). The assays were utilized to support a clinical study in which a microdosing approach was used to

  10. Exposure to inorganic arsenic is associated with increased mitochondrial DNA copy number and longer telomere length in peripheral blood.

    Directory of Open Access Journals (Sweden)

    Syeda Shegufta Ameer

    2016-08-01

    Full Text Available Background: Exposure to inorganic arsenic (iAs through drinking water causes cancer. Alterations in mitochondrial DNA copy number (mtDNAcn and telomere length in blood have been associated with cancer risk. We elucidated if arsenic exposure alters mtDNAcn and telomere length in individuals with different arsenic metabolizing capacity.Methods: We studied two groups in the Salta province, Argentina, one in the Puna area of the Andes (N=264, 89% females and one in Chaco (N=169, 75% females. We assessed arsenic exposure as the sum of arsenic metabolites [iAs, methylarsonic acid (MMA, dimethylarsinic acid (DMA] in urine (U-As using high-performance liquid chromatography coupled with hydride generation and inductively coupled plasma mass spectrometry. Efficiency of arsenic metabolism was expressed as percentage of urinary metabolites. MtDNAcn and telomere length were determined in blood by real-time PCR. Results: Median U-As was 196 (5 - 95 percentile: 21 - 537 µg/L in Andes and 80 (5 - 95 percentile: 15 - 1637 µg/L in Chaco. The latter study group had less-efficient metabolism, with higher %iAs and %MMA in urine compared with the Andean group. U-As was significantly associated with increased mtDNAcn (log2 transformed to improve linearity in Chaco (β=0.027 per 100 µg/L, p=0.0085; adjusted for age and sex, but not in Andes (β=0.025, p=0.24. U-As was also associated with longer telomere length in Chaco (β=0.016, p=0.0066 and Andes (β=0.0075, p=0.029. In both populations, individuals with above median %iAs showed significantly higher mtDNAcn and telomere length compared with individuals with below median %iAs. Conclusions: Arsenic was associated with increased mtDNAcn and telomere length, particularly in individuals with less-efficient arsenic metabolism, a group who may have increased risk for arsenic-related cancer.

  11. Plasma concentrations of cortisol and PGF2α metabolite in Danish sows during mating, and intrauterine and conventional insemination

    Directory of Open Access Journals (Sweden)

    Kindahl Hans

    2007-12-01

    Full Text Available Abstract Background The aims of the present work was to study whether there are any relationships between cortisol and PG-metabolite in mated sows or inseminated with the intrauterine technique and compare these to changes occurring in conventionally inseminated sow. Methods Thirty three crossbred sows (Danish Landrace × Danish Large White were fitted with jugular vein catheters through vena auricularis from one of the ears. The sows were randomly divided into three groups (Boar-, IUI- and AI-group and blood samples were collected before, during and after service. In a final evaluation only 25 sows that became pregnant and farrowed piglets at full term were used. Results Cortisol concentrations increased in all groups but Boar-group (n = 8 had a significantly higher cortisol during 10 to 20 min after service than sows in AI-group (n = 8. In mated sows cortisol concentrations peaked at 15 minutes after service. The Boar-group (n = 8 showed no ascending PG-metabolite levels during the whole experiment, while both IUI- and AI-groups (n = 9 and n = 8, respectively had a 2.5-fold increase in PG-metabolite 15 minutes after service. Conclusion In conclusion, mating of sows by a boar results in a greater increase of cortisol than AI and without an elevation of PG-metabolite levels, which was seen in both the inseminated groups. It was also demonstrated that IUI-group had an earlier significant increase of PG-metabolite levels than sows inseminated conventionally. Further investigation using different semen extenders or even different type of insemination catheters might be helpful in understanding the reason for an immediate increase of PG-metabolite after insemination but not after mating.

  12. Plasma concentrations of cortisol and PGF2α metabolite in Danish sows during mating, and intrauterine and conventional insemination

    Science.gov (United States)

    Norrby, Mattias; Madsen, Mads T; Alexandersen, Charlotte Borg; Kindahl, Hans; Madej, Andrzej

    2007-01-01

    Background The aims of the present work was to study whether there are any relationships between cortisol and PG-metabolite in mated sows or inseminated with the intrauterine technique and compare these to changes occurring in conventionally inseminated sow. Methods Thirty three crossbred sows (Danish Landrace × Danish Large White) were fitted with jugular vein catheters through vena auricularis from one of the ears. The sows were randomly divided into three groups (Boar-, IUI- and AI-group) and blood samples were collected before, during and after service. In a final evaluation only 25 sows that became pregnant and farrowed piglets at full term were used. Results Cortisol concentrations increased in all groups but Boar-group (n = 8) had a significantly higher cortisol during 10 to 20 min after service than sows in AI-group (n = 8). In mated sows cortisol concentrations peaked at 15 minutes after service. The Boar-group (n = 8) showed no ascending PG-metabolite levels during the whole experiment, while both IUI- and AI-groups (n = 9 and n = 8, respectively) had a 2.5-fold increase in PG-metabolite 15 minutes after service. Conclusion In conclusion, mating of sows by a boar results in a greater increase of cortisol than AI and without an elevation of PG-metabolite levels, which was seen in both the inseminated groups. It was also demonstrated that IUI-group had an earlier significant increase of PG-metabolite levels than sows inseminated conventionally. Further investigation using different semen extenders or even different type of insemination catheters might be helpful in understanding the reason for an immediate increase of PG-metabolite after insemination but not after mating. PMID:18053237

  13. Plasma concentrations of cortisol and PGF2alpha metabolite in Danish sows during mating, and intrauterine and conventional insemination.

    Science.gov (United States)

    Norrby, Mattias; Madsen, Mads T; Alexandersen, Charlotte Borg; Kindahl, Hans; Madej, Andrzej

    2007-12-05

    The aims of the present work was to study whether there are any relationships between cortisol and PG-metabolite in mated sows or inseminated with the intrauterine technique and compare these to changes occurring in conventionally inseminated sow. Thirty three crossbred sows (Danish Landrace x Danish Large White) were fitted with jugular vein catheters through vena auricularis from one of the ears. The sows were randomly divided into three groups (Boar-, IUI- and AI-group) and blood samples were collected before, during and after service. In a final evaluation only 25 sows that became pregnant and farrowed piglets at full term were used. Cortisol concentrations increased in all groups but Boar-group (n = 8) had a significantly higher cortisol during 10 to 20 min after service than sows in AI-group (n = 8). In mated sows cortisol concentrations peaked at 15 minutes after service. The Boar-group (n = 8) showed no ascending PG-metabolite levels during the whole experiment, while both IUI- and AI-groups (n = 9 and n = 8, respectively) had a 2.5-fold increase in PG-metabolite 15 minutes after service. In conclusion, mating of sows by a boar results in a greater increase of cortisol than AI and without an elevation of PG-metabolite levels, which was seen in both the inseminated groups. It was also demonstrated that IUI-group had an earlier significant increase of PG-metabolite levels than sows inseminated conventionally. Further investigation using different semen extenders or even different type of insemination catheters might be helpful in understanding the reason for an immediate increase of PG-metabolite after insemination but not after mating.

  14. Development and Validation of an HPLC Method for Simultaneous Quantification of Clopidogrel Bisulfate, Its Carboxylic Acid Metabolite, and Atorvastatin in Human Plasma: Application to a Pharmacokinetic Study

    Directory of Open Access Journals (Sweden)

    Octavian Croitoru

    2015-01-01

    Full Text Available A simple, sensitive, and specific reversed phase liquid chromatographic method was developed and validated for simultaneous quantification of clopidogrel, its carboxylic acid metabolite, and atorvastatin in human serum. Plasma samples were deproteinized with acetonitrile and ibuprofen was chosen as internal standard. Chromatographic separation was performed on an BDS Hypersil C18 column (250 × 4.6 mm; 5 μm via gradient elution with mobile phase consisting of 10 mM phosphoric acid (sodium buffer solution (pH = 2.6 adjusted with 85% orthophosphoric acid : acetonitrile : methanol with flow rate of 1 mL·min−1. Detection was achieved with PDA detector at 220 nm. The method was validated in terms of linearity, sensitivity, precision, accuracy, limit of quantification, and stability tests. Calibration curves of the analytes were found to be linear in the range of 0.008–2 μg·mL−1 for clopidogrel, 0.01–4 μg·mL−1 for its carboxylic acid metabolite, and 0.005–2.5 μg·mL−1 for atorvastatin. The results of accuracy (as recovery with ibuprofen as internal standard were in the range of 96–98% for clopidogrel, 94–98% for its carboxylic acid metabolite, and 90–99% for atorvastatin, respectively.

  15. Plasma cortisol and faecal cortisol metabolites concentrations in stereotypic and non-stereotypic horses: do stereotypic horses cope better with poor environmental conditions?

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    Fureix Carole

    2013-01-01

    Full Text Available Abstract Background Stereotypic behaviours, i.e. repetitive behaviours induced by frustration, repeated attempts to cope and/or brain dysfunction, are intriguing as they occur in a variety of domestic and captive species without any clear adaptive function. Among the different hypotheses, the coping hypothesis predicts that stereotypic behaviours provide a way for animals in unfavourable environmental conditions to adjust. As such, they are expected to have a lower physiological stress level (glucocorticoids than non-stereotypic animals. Attempts to link stereotypic behaviours with glucocorticoids however have yielded contradictory results. Here we investigated correlates of oral and motor stereotypic behaviours and glucocorticoid levels in two large samples of domestic horses (NStudy1 = 55, NStudy2 = 58, kept in sub-optimal conditions (e.g. confinement, social isolation, and already known to experience poor welfare states. Each horse was observed in its box using focal sampling (study 1 and instantaneous scan sampling (study 2. Plasma samples (collected in study 1 but also non-invasive faecal samples (collected in both studies were retrieved in order to assess cortisol levels. Results Results showed that 1 plasma cortisol and faecal cortisol metabolites concentrations did not differ between horses displaying stereotypic behaviours and non-stereotypic horses and 2 both oral and motor stereotypic behaviour levels did not predict plasma cortisol or faecal cortisol metabolites concentrations. Conclusions Cortisol measures, collected in two large samples of horses using both plasma sampling as well as faecal sampling (the latter method minimizing bias due to a non-invasive sampling procedure, therefore do not indicate that stereotypic horses cope better, at least in terms of adrenocortical activity.

  16. Quantification of sibutramine and its two metabolites in human plasma by LC–ESI-MS/MS and its application in a bioequivalence study

    Directory of Open Access Journals (Sweden)

    Venkata Suresh Ponnuru

    2012-08-01

    Full Text Available Obesity can be considered as a chronic illness of epidemic proportion and its incidents have increased exponentially in recent years. The use of anti-obesity drugs such as sibutramine is somewhat helpful. There is a need to quantify such drugs in biological samples, which is generally quite difficult. In this report, we developed and validated a simple, sensitive and specific liquid chromatography–tandem mass spectrometry (LC–MS/MS method for the quantification of sibutramine (SB and its two metabolites N-des methyl sibutramine (DSB and N-di desmethyl sibutramine (DDSB in human plasma. Zorbax SB-C18 (4.6 mm×75 mm, 3.5 μm, 80 Å analytical column and 5 mM ammonium formate:acetonitrile (10:90, v/v mobile phase were used for chromatographic separation of SB, DSB and DDSB. Multiple reaction monitoring (MRM in the positive mode was used to detect SB, DSB and DDSB at m/z 280.3/124.9, 266.3/125.3 and 252.2/124.9, respectively. Liquid–liquid extraction was used for the extraction of analytes and internal standard from human plasma. This method was validated over a linear concentration range of 10.0–10,000.0 pg/mL for SB, DSB and DDSB with correlation coefficients (r of ≥0.9997. The drug and the two metabolites were stable in plasma samples. The validated method was successfully applied in a bioequivalence and pharmacokinetic study with human volunteers under fasting condition. Keywords: LC–ESI-MS/MS, Sibutramine, Human plasma, Bioequivalence, Pharmacokinetic study

  17. Arsenic Species in Edible Seaweeds Using In Vitro Biomimetic Digestion Determined by High-Performance Liquid Chromatography Inductively Coupled Plasma Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Yan-Fang Zhao

    2014-01-01

    Full Text Available Arsenite [As (III], arsenate [As (V], methylarsonate (MMA, and dimethylarsinate (DMA in five edible seaweeds (the brown algae Laminaria japonica, red algae Porphyra yezoensis, brown algae Undaria pinnatifida, brown algae Hizikia fusiformis, and green algae Enteromorpha prolifera were analyzed using in vitro digestion method determined by high-performance liquid chromatography inductively coupled plasma mass spectrometry. The results showed that DMA was found in the water extracts of all samples; As (III were detected in L. japonica and U. pinnatifida and about 23.0 and 0.15 mg/kg of As (V were found in H. fusiformis and E. prolifera respectively. However, after the gastrointestinal digestion, As (V was not detected in any of the five seaweeds. About 0.19 and 1.47 mg/kg of As (III was detected in the gastric extracts of L. japonica and H. fusiformis, respectively, and about 0.31 and 0.10 mg/kg of As (III were extracted from the intestinal extracts of Porphyra yezoensis and U. pinnatifida, respectively. The present results successfully reveal the differences of As species and levels in the water and biomimetic extracts of five edible seaweeds. The risk assessment of the inorganic arsenic in the five edible seaweeds based on present data showed almost no hazards to human health.

  18. Determination of ketamine and its main metabolites by liquid chromatography coupled to tandem mass spectrometry in pig plasma: Comparison of extraction methods.

    Science.gov (United States)

    Ramiole, Cindy; D'Hayer, Benoit; Boudy, Vincent; Legagneux, Josette; Fonsart, Julien; Houzé, Pascal

    2017-11-30

    A rapid, sensitive and specific liquid chromatography coupled to tandem mass spectrometry method was developed for the simultaneous quantification pig plasma of ketamine and its two principal metabolites, norketamine and dehydronorketamine. Three extraction procoles were assessed including acetonitrile precipitation, Oase™ microplate extraction, and liquid-liquid extraction. Oase™ microplate extraction induced no significant matrix effect, important signal/noise ratio and good recoveries, ranging from 82 to 87% for the considered compounds. Using this extraction procedure, the assay was linear in the dynamic range 10-3000ng/mL (R 2 >0.99) regardless of the analytes. Intra- and inter-day accuracies were less than 12% for all compounds and intra- and inter-day precisions expressed as RSD were within ketamine, norketamine and dehydronorketamine concentrations up to 15,000ng/mL can be determined with good precision using appropriate sample dilution. The assay was successfully applied to pig plasma samples to determine the pharmacokinetics of ketamine and the consecutive metabolites after buccal administration of a 4mg/kg ketamine base solutions. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Influence of a ketogenic diet, fish-oil, and calorie restriction on plasma metabolites and lipids in C57BL/6J mice

    Science.gov (United States)

    2014-01-01

    Background Diet therapies including calorie restriction, ketogenic diets, and fish-oil supplementation have been used to improve health and to treat a variety of neurological and non-neurological diseases. Methods We investigated the effects of three diets on circulating plasma metabolites (glucose and β-hydroxybutyrate), hormones (insulin and adiponectin), and lipids over a 32-day period in C57BL/6J mice. The diets evaluated included a standard rodent diet (SD), a ketogenic diet (KD), and a standard rodent diet supplemented with fish-oil (FO). Each diet was administered in either unrestricted (UR) or restricted (R) amounts to reduce body weight by 20%. Results The KD-UR increased body weight and glucose levels and promoted a hyperlipidemic profile, whereas the FO-UR decreased body weight and glucose levels and promoted a normolipidemic profile, compared to the SD-UR. When administered in restricted amounts, all three diets produced a similar plasma metabolite profile, which included decreased glucose levels and a normolipidemic profile. Linear regression analysis showed that circulating glucose most strongly predicted body weight and triglyceride levels, whereas calorie intake moderately predicted glucose levels and strongly predicted ketone body levels. Conclusions These results suggest that biomarkers of health can be improved when diets are consumed in restricted amounts, regardless of macronutrient composition. PMID:24910707

  20. Serotonin syndrome following sibutramine poisoning in a child, with sequential quantification of sibutramine and its primary and secondary amine metabolites in plasma.

    Science.gov (United States)

    Bucaretchi, Fábio; de Capitani, Eduardo Mello; Mello, Sueli Moreira; Lanaro, Rafael; Barros, Roberta F; Fernandes, Luciane C R; da Costa, José Luiz; Hyslop, Stephen

    2009-07-01

    To report a case of serotonin syndrome (SS) after sibutramine overdose in a child. A 4-year-old girl was admitted 25 h after accidentally ingesting approximately 27 pills of sibutramine (15 mg, approximately 23 mg/kg). The child developed clinical features suggestive of SS, including diaphoresis, tachycardia, hypertension, agitation, insomnia, incoordination, hypertonia (lower limbs > upper limbs), and hallucinations. Serum creatine phosphokinase levels reached a peak on day 3 (2,577 U/L, reference value sibutramine and the active metabolites, M1 (mono-desmethyl sibutramine) and M2 (di-desmethyl sibutramine), by liquid chromatography/electrospray ionization tandem mass spectrometry in six sequential samples collected from 25 to 147 h post-ingestion revealed a nonlinear decrease in the log-scale plasma concentrations. Treatment was only supportive and involved prolonged sedation to control the agitation, sleeplessness, and hypertension; no cyproheptadine was used. The patient was discharged on day 6 and follow-up revealed no sequelae. To our knowledge, this is the first report of SS after sibutramine overdose in a child, with sequential monitoring of the plasma levels of the drug and its two active metabolites. The growing consumption of weight reducing pills may increase the risk of unintentional acute toxic exposures in children.

  1. Effect of intake on fasting heat production, respiratory quotient and plasma metabolites measured using the washed rumen technique

    Science.gov (United States)

    The objective was to investigate the effect of intake prior to fasting on concentrations of metabolites and hormones, respiratory quotient (RQ) and fasting heat production (HP) using the washed rumen technique and to compare these values with those from the fed state. Six Holstein steers (360 ± 22 k...

  2. Simultaneous quantification of PGI2 and TXA2 metabolites in plasma and urine in NO-deficient mice by a novel UHPLC/MS/MS method.

    Science.gov (United States)

    Kij, Agnieszka; Mateuszuk, Lukasz; Sitek, Barbara; Przyborowski, Kamil; Zakrzewska, Agnieszka; Wandzel, Krystyna; Walczak, Maria; Chlopicki, Stefan

    2016-09-10

    The balance between vascular prostacyclin (PGI2) generated mainly via cyclooxygenase-2 (COX-2) and its physiological antagonist platelet-derived thromboxane A2 (TXA2) formed by cyclooxygenase-1 (COX-1) determines cardiovascular homeostasis. In the present work, a novel bioanalytical method for simultaneous quantification of stable plasma and urinary metabolites of PGI2 (6-keto-PGF1α, 2,3-dinor-6-keto-PGF1α) and TXA2 (TXB2, 2,3-dinor-TXB2) using ultra high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC/MS/MS) was developed. The method was validated using artificial plasma and urine and linearity range, intra- and inter-day precision and accuracy, recovery of analytes, relative and absolute matrix effect and stability of analytes were determined. The use of artificial biofluids improved the method sensitivity as it eliminated the contribution of endogenous metabolites present in mice plasma and urine to validation procedure. The newly developed and validated method allowed to quantify 6-keto-PGF1α and TXB2 in mice plasma as well as 2,3-dinor-6-keto-PGF1α and 2,3-dinor-TXB2 in urine samples with high sensitivity and accuracy. The calibration range was established from 0.1 to 100ng/mL for all analytes using artificial biofluids and the recoveries were greater than 89.9%. All validated parameters met the criteria of acceptance specified in FDA and EMA guidance. This method was successfully employed for profiling of the changes in PGI2 and TXA2 generation in NO-deficient mice. This work demonstrated that NO-deficiency induced by L-NAME, evidenced by a fall in nitrite in plasma and urine, was associated with platelet activation, robust increase in TXB2 and mild increase in 6-keto-PGF1α concentration in plasma. Changes in 2,3-dinor-6-keto-PGF1α and 2,3-dinor-TXB2 concentration in urine were less evident suggesting that the measurements in plasma better reflect modest changes in PGI2/TXA2 homeostasis than measurements in urine

  3. Development and validation of a high performance liquid chromatography quantification method of levo-tetrahydropalmatine and its metabolites in plasma and brain tissues: application to a pharmacokinetic study.

    Science.gov (United States)

    Abdallah, Inas A; Huang, Peng; Liu, Jing; Lee, David Y; Liu-Chen, Lee-Yuan; Hassan, Hazem E

    2017-04-01

    Levo-tetrahydropalmatine (l-THP) is an alkaloid isolated from Chinese medicinal herbs of the Corydalis and Stephania genera. It has been used in China for more than 40 years mainly as an analgesic with sedative/hypnotic effects. Despite its extensive use, its metabolism has not been quantitatively studied, nor there a sensitive reliable bioanalytical method for its quantification simultaneously with its metabolites. As such, the objective of this study was to develop and validate a sensitive and selective HPLC method for simultaneous quantification of l-THP and its desmethyl metabolites l-corydalmine (l-CD) and l-corypalmine (l-CP) in rat plasma and brain tissues. Rat plasma and brain samples were processed by liquid-liquid extraction using ethyl acetate. Chromatographic separation was achieved on a reversed-phase Symmetry® C 18 column (4.6 × 150 mm, 5 μm) at 25°C. The mobile phase consisted of acetonitrile-methanol-10 mm ammonium phosphate (pH 3) (10:30:60, v/v) and was used at a flow rate of 0.8 mL/min. The column eluent was monitored at excitation and emission wavelengths of 230 and 315 nm, respectively. The calibration curves were linear over the concentration range of 1-10,000 ng/mL. The intra- and interday reproducibility studies demonstrated accuracy and precision within the acceptance criteria of bioanalytical guidelines. The validated HPLC method was successfully applied to analyze samples from a pharmacokinetic study of l-THP in rats. Taken together, the developed method can be applied for bioanalysis of l-THP and its metabolites in rodents and potentially can be transferred for bioanalysis of human samples. Copyright © 2016 John Wiley & Sons, Ltd.

  4. An insight of environmental contamination of arsenic on animal health

    Directory of Open Access Journals (Sweden)

    Paramita Mandal

    2017-03-01

    Full Text Available The main threats to human health from heavy metals are associated with exposure to lead, cadmium, mercury and arsenic. Exposure to arsenic is mainly via intake of food and drinking water, food being the most important source in most populations. Although adverse health effects of heavy metals have been known for a long time, exposure to heavy metals continues and is even increasing in some areas. Long-term exposure to arsenic in drinking-water is mainly related to increased risks of skin cancer, but also some other cancers, as well as other skin lesions such as hyperkeratosis and pigmentation changes. Therefore, measures should be taken to reduce arsenic exposure in the general population in order to minimize the risk of adverse health effects. Animal are being exposed to arsenic through contaminated drinking water, feedstuff, grasses, vegetables and different leaves. Arsenic has been the most common causes of inorganic chemical poisoning in farm animals. Although, sub-chronic and chronic exposure of arsenic do not generally reveal external signs or symptoms in farm animals but arsenic (or metabolites concentrations in blood, hair, hoofs and urine are remained high in animals of arsenic contaminated zones. So it is assumed that concentration of arsenic in blood, urine, hair or milk have been used as biomarkers of arsenic exposure in field animals.

  5. Sensitive method for the quantitative determination of proguanil and its metabolites in rat blood and plasma by liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Leveque, Nathalie L; Charman, William N; Chiu, Francis C K

    2006-01-18

    A sensitive, simple and fast liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for the determination of proguanil (PG) and its metabolites, cycloguanil (CG) and 1-(4-chlorophenyl)biguanide (4CPB), was developed and validated over a concentration range of 1-2000 ng/mL using only 50 microL of blood or plasma. After a simple solvent precipitation procedure, the supernatant was analysed directly by HPLC-MS/MS. Separation was achieved using an ethyl-linked phenyl reverse phase column with polar endcapping with an acetonitrile-water-formic acid gradient. Mass spectrometry was performed using a triple quadrupole mass spectrometer operating in positive electrospray ionization mode. The elution of PG (254.07-->169.99), CG (252.12-->195.02) and 4CPB (212.06-->153.06) was monitored using selected reaction monitoring. The three compounds and the internal standard (chloroproguanil) were well separated by HPLC and no interfering peaks were detected at the usual concentrations found in blood and plasma. The limit of quantification of PG and CG was 1 ng/mL and 5 ng/mL for 4CPB in rat blood and plasma. The extraction efficiency of PG, CG and 4CPB from rat blood and plasma was higher than 73%. The intra- and inter-assay variability of PG, CG and 4CPB were within 12% and the accuracy within +/-5%. This new assay offers higher sensitivity and a much shorter run time over earlier methods.

  6. Methylated trivalent arsenicals are potent inhibitors of glucose stimulated insulin secretion by murine pancreatic islets

    Energy Technology Data Exchange (ETDEWEB)

    Douillet, Christelle [Department of Nutrition, Gillings School of Global Public Health, 2302 MHRC, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7461 (United States); Currier, Jenna [Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7461 (United States); Saunders, Jesse [Department of Nutrition, Gillings School of Global Public Health, 2302 MHRC, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7461 (United States); Bodnar, Wanda M. [Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7431 (United States); Matoušek, Tomáš [Institute of Analytical Chemistry of the ASCR, v.v.i., Veveří 97, 602 00 Brno (Czech Republic); Stýblo, Miroslav, E-mail: styblo@med.unc.edu [Department of Nutrition, Gillings School of Global Public Health, 2302 MHRC, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7461 (United States)

    2013-02-15

    Epidemiologic evidence has linked chronic exposure to inorganic arsenic (iAs) with an increased prevalence of diabetes mellitus. Laboratory studies have identified several mechanisms by which iAs can impair glucose homeostasis. We have previously shown that micromolar concentrations of arsenite (iAs{sup III}) or its methylated trivalent metabolites, methylarsonite (MAs{sup III}) and dimethylarsinite (DMAs{sup III}), inhibit the insulin-activated signal transduction pathway, resulting in insulin resistance in adipocytes. Our present study examined effects of the trivalent arsenicals on insulin secretion by intact pancreatic islets isolated from C57BL/6 mice. We found that 48-hour exposures to low subtoxic concentrations of iAs{sup III}, MAs{sup III} or DMAs{sup III} inhibited glucose-stimulated insulin secretion (GSIS), but not basal insulin secretion. MAs{sup III} and DMAs{sup III} were more potent than iAs{sup III} as GSIS inhibitors with estimated IC{sub 50} ≤ 0.1 μM. The exposures had little or no effects on insulin content of the islets or on insulin expression, suggesting that trivalent arsenicals interfere with mechanisms regulating packaging of the insulin transport vesicles or with translocation of these vesicles to the plasma membrane. Notably, the inhibition of GSIS by iAs{sup III}, MAs{sup III} or DMAs{sup III} could be reversed by a 24-hour incubation of the islets in arsenic-free medium. These results suggest that the insulin producing pancreatic β-cells are among the targets for iAs exposure and that the inhibition of GSIS by low concentrations of the methylated metabolites of iAs may be the key mechanism of iAs-induced diabetes. - Highlights: ► Trivalent arsenicals inhibit glucose stimulated insulin secretion by pancreatic islets. ► MAs{sup III} and DMAs{sup III} are more potent inhibitors than arsenite with IC{sub 50} ∼ 0.1 μM. ► The arsenicals have little or no effects on insulin expression in pancreatic islets. ► The inhibition of

  7. Methylated trivalent arsenicals are potent inhibitors of glucose stimulated insulin secretion by murine pancreatic islets

    International Nuclear Information System (INIS)

    Douillet, Christelle; Currier, Jenna; Saunders, Jesse; Bodnar, Wanda M.; Matoušek, Tomáš; Stýblo, Miroslav

    2013-01-01

    Epidemiologic evidence has linked chronic exposure to inorganic arsenic (iAs) with an increased prevalence of diabetes mellitus. Laboratory studies have identified several mechanisms by which iAs can impair glucose homeostasis. We have previously shown that micromolar concentrations of arsenite (iAs III ) or its methylated trivalent metabolites, methylarsonite (MAs III ) and dimethylarsinite (DMAs III ), inhibit the insulin-activated signal transduction pathway, resulting in insulin resistance in adipocytes. Our present study examined effects of the trivalent arsenicals on insulin secretion by intact pancreatic islets isolated from C57BL/6 mice. We found that 48-hour exposures to low subtoxic concentrations of iAs III , MAs III or DMAs III inhibited glucose-stimulated insulin secretion (GSIS), but not basal insulin secretion. MAs III and DMAs III were more potent than iAs III as GSIS inhibitors with estimated IC 50 ≤ 0.1 μM. The exposures had little or no effects on insulin content of the islets or on insulin expression, suggesting that trivalent arsenicals interfere with mechanisms regulating packaging of the insulin transport vesicles or with translocation of these vesicles to the plasma membrane. Notably, the inhibition of GSIS by iAs III , MAs III or DMAs III could be reversed by a 24-hour incubation of the islets in arsenic-free medium. These results suggest that the insulin producing pancreatic β-cells are among the targets for iAs exposure and that the inhibition of GSIS by low concentrations of the methylated metabolites of iAs may be the key mechanism of iAs-induced diabetes. - Highlights: ► Trivalent arsenicals inhibit glucose stimulated insulin secretion by pancreatic islets. ► MAs III and DMAs III are more potent inhibitors than arsenite with IC 50 ∼ 0.1 μM. ► The arsenicals have little or no effects on insulin expression in pancreatic islets. ► The inhibition of insulin secretion by arsenite, MAs III or DMAs III is reversible. ► Thus

  8. Experimental manipulation of dietary arsenic levels in great tit nestlings: Accumulation pattern and effects on growth, survival and plasma biochemistry.

    Science.gov (United States)

    Sánchez-Virosta, Pablo; Espín, Silvia; Ruiz, Sandra; Salminen, Juha-Pekka; García-Fernández, Antonio J; Eeva, Tapio

    2018-02-01

    Arsenic (As) is a ubiquitous metalloid classified as one of the most hazardous substances, but information about its exposure and effects in free-living passerines is lacking. The aim of this study is to elucidate the effect of an As manipulation experiment on survival, growth and physiology of great tits (Parus major). Wild P. major nestlings inhabiting an unpolluted area were dosed with water, 0.2 or 1 μg g -1  d -1 of sodium arsenite (Control, Low and High As groups), whereas those living in a metal-polluted area were dosed with water (Smelter group). Birds accumulated As in tissues (liver, bone and feathers) in a dose-dependent way. Nestlings exposed to 1 μg g -1  d -1 of sodium arsenite showed reduced number of fledglings per successful nest, and those exposed to 0.2 μg g -1  d -1 had reduced wing growth, which could have post-fledging consequences such as increased predation risk. These results suggest that the LOAEL for effects on nestling survival and development in great tits is likely equal to or below 1 μg g -1  d -1 . However, limited effects on the biochemical parameters evaluated were found. It has been shown that As may produce oxidative stress and tissue damage, so further research exploring this issue will be carried out in a future study. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Metabolomic characteristics of arsenic-associated diabetes in a prospective cohort in Chihuahua, Mexico.

    Science.gov (United States)

    Martin, Elizabeth; González-Horta, Carmen; Rager, Julia; Bailey, Kathryn A; Sánchez-Ramírez, Blanca; Ballinas-Casarrubias, Lourdes; Ishida, María C; Gutiérrez-Torres, Daniela S; Hernández Cerón, Roberto; Viniegra Morales, Damián; Baeza Terrazas, Francisco A; Saunders, R Jesse; Drobná, Zuzana; Mendez, Michelle A; Buse, John B; Loomis, Dana; Jia, Wei; García-Vargas, Gonzalo G; Del Razo, Luz M; Stýblo, Miroslav; Fry, Rebecca

    2015-04-01

    Chronic exposure to inorganic arsenic (iAs) has been linked to an increased risk of diabetes, yet the specific disease phenotype and underlying mechanisms are poorly understood. In the present study we set out to identify iAs exposure-associated metabolites with altered abundance in nondiabetic and diabetic individuals in an effort to understand the relationship between exposure, metabolomic response, and disease status. A nested study design was used to profile metabolomic shifts in urine and plasma collected from 90 diabetic and 86 nondiabetic individuals matched for varying iAs concentrations in drinking water, body mass index, age, and sex. Diabetes diagnosis was based on measures of fasting plasma glucose and 2-h blood glucose. Multivariable models were used to identify metabolites with altered abundance associated with iAs exposure among diabetic and nondiabetic individuals. A total of 132 metabolites were identified to shift in urine or plasma in response to iAs exposure characterized by the sum of iAs metabolites in urine (U-tAs). Although many metabolites were altered in both diabetic and nondiabetic 35 subjects, diabetic individuals displayed a unique response to iAs exposure with 59 altered metabolites including those that play a role in tricarboxylic acid cycle and amino acid metabolism. Taken together, these data highlight the broad impact of iAs exposure on the human metabolome, and demonstrate some specificity of the metabolomic response between diabetic and nondiabetic individuals. These data may provide novel insights into the mechanisms and phenotype of diabetes associated with iAs exposure. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Oral fluid and plasma 3,4-methylenedioxymethamphetamine (MDMA) and metabolite correlation after controlled oral MDMA administration.

    Science.gov (United States)

    Desrosiers, Nathalie A; Barnes, Allan J; Hartman, Rebecca L; Scheidweiler, Karl B; Kolbrich-Spargo, Erin A; Gorelick, David A; Goodwin, Robert S; Huestis, Marilyn A

    2013-05-01

    Oral fluid (OF) offers a noninvasive sample collection for drug testing. However, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) in OF has not been adequately characterized in comparison to plasma. We administered oral low-dose (1.0 mg/kg) and high-dose (1.6 mg/kg) MDMA to 26 participants and collected simultaneous OF and plasma specimens for up to 143 h after dosing. We compared OF/plasma (OF/P) ratios, time of initial detection (t first), maximal concentrations (C max), time of peak concentrations (t max), time of last detection (t last), clearance, and 3,4-methylenedioxyamphetamine (MDA)-to-MDMA ratios over time. For OF MDMA and MDA, C max was higher, t last was later, and clearance was slower compared to plasma. For OF MDA only, t first was later compared to plasma. Median (range) OF/P ratios were 5.6 (0.1-52.3) for MDMA and 3.7 (0.7-24.3) for MDA. OF and plasma concentrations were weakly but significantly correlated (MDMA: R(2) = 0.438, MDA: R(2) = 0.197, p MDMA low = 5.2 (0.1-40.4), high = 6.0 (0.4-52.3, p MDMA ratios in plasma were higher than those in OF (p MDMA ratios significantly increased over time in OF and plasma. The MDMA and MDA concentrations were higher in OF than in plasma. OF and plasma concentrations were correlated, but large inter-subject variability precludes the estimation of plasma concentrations from OF.

  11. Simultaneous quantification of lenalidomide, ibrutinib and its active metabolite PCI-45227 in rat plasma by LC-MS/MS: application to a pharmacokinetic study.

    Science.gov (United States)

    Veeraraghavan, Sridhar; Viswanadha, Srikant; Thappali, Satheeshmanikandan; Govindarajulu, Babu; Vakkalanka, Swaroopkumar; Rangasamy, Manivannan

    2015-03-25

    Efficacy assessments using a combination of ibrutinib and lenalidomide necessitate the development of an analytical method for determination of both drugs in plasma with precision. A high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of lenalidomide, ibrutinib, and its active metabolite PCI45227 in rat plasma. Extraction of lenalidomide, ibrutinib, PCI45227 and tolbutamide (internal standard; IS) from 50 μl rat plasma was carried out by liquid-liquid extraction with ethyl acetate:dichloromethane (90:10) ratio. Chromatographic separation of analytes was performed on YMC pack ODS AM (150 mm × 4.6 mm, 5 μm) column under gradient conditions with acetonitrile:0.1% formic acid buffer as the mobile phases at a flow rate of 1 ml/min. Precursor ion and product ion transition for analytes and IS were monitored on a triple quadrupole mass spectrometer, operated in the selective reaction monitoring with positive ionization mode. Method was validated over a concentration range of 0.72-183.20 ng/ml for ibrutinib, 0.76-194.33 ng/ml for PCI-45227 and 1.87-479.16 ng/ml for lenalidomide. Mean extraction recovery for ibrutinib, PCI-45227, lenalidomide and IS of 75.2%, 84.5%, 97.3% and 92.3% were consistent across low, medium, and high QC levels. Precision and accuracy at low, medium and high quality control levels were less than 15% across analytes. Bench top, wet, freeze-thaw and long term stability was evaluated for all the analytes. The analytical method was applied to support a pharmacokinetic study of simultaneous estimation of lenalidomide, ibrutinib, and its active metabolite PCI-45227 in Wistar rat. Assay reproducibility was demonstrated by re-analysis of 18 incurred samples. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. An Atmospheric Pressure Chemical Ionization MS/MS Assay Using Online Extraction for the Analysis of 11 Cannabinoids and Metabolites in Human Plasma and Urine.

    Science.gov (United States)

    Klawitter, Jelena; Sempio, Cristina; Mörlein, Sophie; De Bloois, Erik; Klepacki, Jacek; Henthorn, Thomas; Leehey, Maureen A; Hoffenberg, Edward J; Knupp, Kelly; Wang, George S; Hopfer, Christian; Kinney, Greg; Bowler, Russell; Foreman, Nicholas; Galinkin, Jeffrey; Christians, Uwe; Klawitter, Jost

    2017-10-01

    Although, especially in the United States, there has been a recent surge of legalized cannabis for either recreational or medicinal purposes, surprisingly little is known about clinical dose-response relationships, pharmacodynamic and toxicodynamic effects of cannabinoids such as Δ9-tetrahydrocannabinol (THC). Even less is known about other active cannabinoids. To address this knowledge gap, an online extraction, high-performance liquid chromatography coupled with tandem mass spectrometry method for simultaneous quantification of 11 cannabinoids and metabolites including THC, 11-hydroxy-Δ9-tetrahydrocannabinol, 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid, 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide (THC-C-gluc), cannabinol, cannabidiol, cannabigerol, cannabidivarin, Δ9-tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-Δ9-tetrahydrocannabivarin (THCV-COOH) was developed and validated in human urine and plasma. In contrast to atmospheric pressure chemical ionization, electrospray ionization was associated with extensive ion suppression in plasma and urine samples. Thus, the atmospheric pressure chemical ionization assay was validated showing a lower limit of quantification ranging from 0.39 to 3.91 ng/mL depending on study compound and matrix. The upper limit of quantification was 400 ng/mL except for THC-C-gluc with an upper limit of quantification of 2000 ng/mL. The linearity was r > 0.99 for all analyzed calibration curves. Acceptance criteria for intrabatch and interbatch accuracy (85%-115%) and imprecision (<15%) were met for all compounds. In plasma, the only exceptions were THCV (75.3%-121.2% interbatch accuracy) and cannabidivarin (interbatch imprecision, 15.7%-17.2%). In urine, THCV did not meet predefined acceptance criteria for intrabatch accuracy. This assay allows for monitoring not only THC and its major metabolites but also major cannabinoids that are of interest for marijuana research and clinical practice.

  13. Simultaneous determination of flurbiprofen and its hydroxy metabolite in human plasma by liquid chromatography-tandem mass spectrometry for clinical application.

    Science.gov (United States)

    Lee, Hye-In; Choi, Chang-Ik; Byeon, Ji-Yeong; Lee, Jung-Eun; Park, So-Young; Kim, Young-Hoon; Kim, Se-Hyung; Lee, Yun-Jeong; Jang, Choon-Gon; Lee, Seok-Yong

    2014-11-15

    Flurbiprofen (FLB) is one of the phenylalkanoic acid derivatives of non-steroidal anti-inflammatory drugs used for the management of pain and inflammation in patients with arthritis. We developed and validated a rapid and sensitive high-performance liquid chromatography analytical method utilizing tandem mass spectrometry (HPLC-MS/MS) for the simultaneous determination of FLB and its major metabolite, 4'-hydroxyflurbiprofen (4'-OH-FLB), in human plasma. Probenecid was used as an internal standard (IS). After liquid-liquid extraction with methyl t-butyl ether, chromatographic separation of the two analytes was achieved using a reversed-phase Luna C18 column (2.0mm×50mm, 5μm particles) with a mobile phase of 10mM ammonium formate buffer (pH 3.5)-methanol (15:85, v/v) and quantified by MS/MS detection in ESI negative ion mode. The flow rate of the mobile phase was 250μl/min and the retention times of FLB, 4'-OH-FLB, and IS were 1.1, 0.8, and 0.9min, respectively. The calibration curves were linear over a range of 0.01-10μg/ml for FLB and 0.01-1μg/ml for 4'-OH-FLB. The lower limit of quantifications using 100μl of human plasma was 0.01μg/ml for both analytes. The mean accuracy and precision for intra- and inter-run validation of FLB and 4'-OH-FLB were all within acceptable limits. The present HPLC-MS/MS method showed improved sensitivity for quantification of the FLB and its major metabolite in human plasma compared with previously described analytical methods. The validated method was successfully applied to a pharmacokinetic study in humans. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. A liquid chromatography with tandem mass spectrometry method for simultaneous determination of UTL-5g and its metabolites in human plasma.

    Science.gov (United States)

    Shaw, Jiajiu; Wiegand, Richard; Wu, Jianmei; Bao, Xun; Valeriote, Frederick; Li, Jing

    2015-06-01

    UTL-5g is a novel small-molecule TNF-α inhibitor under investigation as both a chemoprotective and radioprotective agent. Animal studies showed that pretreatment of UTL-5g protected kidney, liver, and platelets from cisplatin-induced toxicity. In addition, UTL-5g reduced liver and lung injuries induced by radiation in vivo. Although a number of preclinical studies have been conducted, a validated bioanalytical method for UTL-5g in human plasma has not been published. In this work, a sensitive and reproducible reverse-phase liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) assay was developed and validated for the determination of UTL-5g and its metabolites, 5-methylisoxazole-3-carboxylic acid (ISOX) and 2,4-dichloroaniline (DCA), in human plasma. The method involves a simple methanol precipitation step followed by injection of the supernatant onto a Waters 2695 HPLC system coupled with a Waters Quattro Micro™ triple quadrupole mass spectrometer. Chromatographic separation was accomplished using a Waters Nova-Pak C18 column maintained at 30°C, running at gradient mode with mobile phase consisting of 0.1% formic acid in water and 0.1% formic acid in methanol at a flow rate of 0.2mL/min. The analytes were monitored under positive electrospray ionization (ESI). Quantitation of these compounds in plasma was linear from 0.05 to 10μM. The lower limit of quantitation (LLOQ) was 0.05, 0.1, and 0.2μM for UTL-5g, ISOX and DCA, respectively. The accuracy and intra-and inter-day precisions were within the generally accepted criteria for bioanalytical method (5g and its metabolites, ISOX and DCA. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Vitamin D-metabolites from human plasma and mass spectrometric analysis by fast heavy ion induced desorption

    Energy Technology Data Exchange (ETDEWEB)

    Fohlman, J; Peterson, P A [Uppsala Univ. (Sweden). Dept. of Cell Research; Kamensky, I; Hakansson, P; Sundqvist, B [Tandemacceleratorlaboratoriet, Uppsala (Sweden)

    1982-07-01

    D-vitamin metabolites have been isolated from human serum employing chromatographic techniques. The serum carrier protein for vitamin D (DBP) was first isolated by immunosorbent chromatography. Lipid ligands associated with DBP were then extracted with hexane and separated by high pressure liquid chromatography (HPLC). Detection of vitamin D metabolites by their absorbance of ultraviolet light is not sufficiently sensitive to monitor all vitamin D derivatives from a few millilitres of serum. Therefore, further analyses are necessary to quantitative these compounds. We have begun to develop a mass spectrometric method to achieve a reliable, quantitative procedure. As a first step towards this goal a number of pure samples of vitamin D compounds have been studied in a time-of-flight mass spectrometer based on fast heavy ion induced desorption. All vitamin D compounds examined could be detected and identified by their molecular ion and fragment spectra.

  16. Vitamin D-metabolites from human plasma and mass spectrometric analysis by fast heavy ion induced desorption

    International Nuclear Information System (INIS)

    Fohlman, J.; Peterson, P.A.

    1982-01-01

    D-vitamin metabolites have been isolated from human serum employing chromatographic techniques. The serum carrier protein for vitamin D (DBP) was first isolated by immunosorbent chromatography. Lipid ligands associated with DBP were then extracted with hexane and separated by high pressure liquid chromatography (HPLC). Detection of vitamin D metabolites by their absorbance of ultraviolet light is not sufficiently sensitive to monitor all vitamin D derivatives from a few millilitres of serum. Therefore, further analyses are necessary to quantitative these compounds. We have begun to develop a mass spectrometric method to achieve a reliable, quantitative procedure. As a first step towards this goal a number of pure samples of vitamin D compounds have been studied in a time-of-flight mass spectrometer based on fast heavy ion induced desorption. All vitamin D compounds examined could be detected and identified by their molecular ion and fragment spectra. (orig.)

  17. Quantitative analysis of the experimental cytotoxic drug cyclopentenyl cytosine and its metabolite in plasma with HPLC tandem mass spectrometry

    NARCIS (Netherlands)

    Schimmel, Kirsten; van Lenthe, Henk; Leen, Rene; Kulik, Willem; Verschuur, Arnauld; Guchelaar, Henk-Jan; van Kuilenburg, André

    2008-01-01

    The cytotoxic drug cyclopentenyl cytosine (CPEC) is currently being investigated in early clinical trials. Monitoring of plasma levels is required for pharmacokinetic analysis and management of toxicity. This paper describes the analysis of CPEC and cyclopentenyl uracil (CPEU) in plasma by

  18. A parallel chiral-achiral liquid chromatographic method for the determination of the stereoisomers of ketamine and ketamine metabolites in the plasma and urine of patients with complex regional pain syndrome.

    Science.gov (United States)

    Moaddel, Ruin; Venkata, Swarajya Lakshmi Vattem; Tanga, Mary J; Bupp, James E; Green, Carol E; Iyer, Lalitha; Furimsky, Anna; Goldberg, Michael E; Torjman, Marc C; Wainer, Irving W

    2010-10-15

    A parallel chiral/achiral LC-MS/MS assay has been developed and validated to measure the plasma and urine concentrations of the enantiomers of ketamine, (R)- and (S)-Ket, in complex regional pain syndrome (CRPS) patients receiving a 5-day continuous infusion of a sub-anesthetic dose of (R,S)-Ket. The method was also validated for the determination of the enantiomers of the Ket metabolites norketamine, (R)- and (S)-norKet and dehydronorketamine, (R)- and (S)-DHNK, as well as the diastereomeric metabolites hydroxynorketamine, (2S,6S)-/(2R,6R)-HNK and two hydroxyketamines, (2S,6S)-HKet and (2S,6R)-Hket. In this method, (R,S)-Ket, (R,S)-norKet and (R,S)-DHNK and the diastereomeric hydroxyl-metabolites were separated and quantified using a C(18) stationary phase and the relative enantiomeric concentrations of (R,S)-Ket, (R,S)-norKet and (R,S)-DHNK were determined using an AGP-CSP. The analysis of the results of microsomal incubations of (R)- and (S)-Ket and a plasma and urine sample from a CRPS patient indicated the presence of 10 additional compounds and glucuronides. The data from the analysis of the patient sample also demonstrated that a series of HNK metabolites were the primary metabolites in plasma and (R)- and (S)-DHNK were the major metabolites found in urine. The results suggest that norKet is the initial, but not the primary metabolite and that downstream norKet metabolites play a role in (R,S)-Ket-related pain relief in CRPS patients. Published by Elsevier B.V.

  19. Contribution of arsenic species in unicellular algae to the cycling of arsenic in marine ecosystems.

    Science.gov (United States)

    Duncan, Elliott G; Maher, William A; Foster, Simon D

    2015-01-06

    This review investigates the arsenic species produced by and found in marine unicellular algae to determine if unicellular algae contribute to the formation of arsenobetaine (AB) in higher marine organisms. A wide variety of arsenic species have been found in marine unicellular algae including inorganic species (mainly arsenate--As(V)), methylated species (mainly dimethylarsenate (DMA)), arsenoribosides (glycerol, phosphate, and sulfate) and metabolites (dimethylarsenoethanol (DMAE)). Subtle differences in arsenic species distributions exist between chlorophyte and heterokontophyte species with As(V) commonly found in water-soluble cell fractions of chlorophyte species, while DMA is more common in heterokontophyte species. Additionally, different arsenoriboside species are found in each phyla with glycerol and phosphate arsenoribosides produced by chlorophytes, whereas glycerol, phosphate, and sulfate arsenoribosides are produced by heterokontophytes, which is similar to existing data for marine macro-algae. Although arsenoribosides are the major arsenic species in many marine unicellular algal species, AB has not been detected in unicellular algae which supports the hypothesis that AB is formed in marine animals via the ingestion and further metabolism of arsenoribosides. The observation of significant DMAE concentrations in some unicellular algal cultures suggests that unicellular algae-based detritus contains arsenic species that can be further metabolized to form AB in higher marine organisms. Future research establishing how environmental variability influences the production of arsenic species by marine unicellular algae and what effect this has on arsenic cycling within marine food webs is essential to clarify the role of these organisms in marine arsenic cycling.

  20. Survey of total and inorganic arsenic content in blue mussels (Mytilus edulis L.) from Norwegian fiords: Revelation of unusual high levels of inorganic arsenic

    DEFF Research Database (Denmark)

    Sloth, Jens Jørgen; Julshamn, Kåre

    2008-01-01

    arsenic. Total arsenic was determined using inductively coupled plasma mass spectrometry (ICPMS) following microwave-assisted acidic digestion of the samples. Inorganic arsenic was determined using an anion-exchange HPLC-ICPMS method following microwave-assisted alkaline solubilization of the samples...

  1. Development and validation of bioanalytical UHPLC-UV method for simultaneous analysis of unchanged fenofibrate and its metabolite fenofibric acid in rat plasma: Application to pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Rayan G. Alamri

    2017-01-01

    Full Text Available A simple, precise, selective and fast ultra-high performance liquid chromatography (UHPLC-UV method has been developed and validated for the simultaneous determination of a lipid regulating agent fenofibrate and its metabolite fenofibric acid in rat plasma. The chromatographic separation was carried out on a reversed-phase Acquity® BEH C18 column using methanol–water (65:35, v/v as the mobile phase. The isocratic flow was 0.3 ml/min with rapid run time of 2.5 min and UV detection was at 284 nm. The method was validated over a concentration range of 100–10000 ng/ml (r2 ⩾ 0.9993. The selectivity, specificity, recovery, accuracy and precision were validated for determination of fenofibrate/fenofibric acid in rat plasma. The lower limits of detection and quantitation of the method were 30 and 90 ng/ml for fenofibrate and 40 and 100 ng/ml for fenofibric acid, respectively. The within and between-day coefficients of variation were less than 5%. The validated method has been successfully applied to measure the plasma concentrations in pharmacokinetics study of fenofibrate in an animal model to illustrate the scope and application of the method.

  2. Ultra-sensitive LC-MS/MS method for the quantification of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine in human plasma for a microdose clinical trial.

    Science.gov (United States)

    van Nuland, M; Hillebrand, M J X; Rosing, H; Burgers, J A; Schellens, J H M; Beijnen, J H

    2018-03-20

    In microdose clinical trials a maximum of 100 μg of drug substance is administered to participants, in order to determine the pharmacokinetic properties of the agents. Measuring low plasma concentrations after administration of a microdose is challenging and requires the use of ulta-sensitive equipment. Novel liquid chromatography-mass spectrometry (LC-MS/MS) platforms can be used for quantification of low drug plasma levels. Here we describe the development and validation of an LC-MS/MS method for quantification of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine (dFdU) in the low picogram per milliliter range to support a microdose trial. The validated assay ranges from 2.5-500 pg/mL for gemcitabine and 250-50,000 pg/mL for dFdU were linear, with a correlation coefficient (r 2 ) of 0.996 or better. Sample preparation with solid phase extraction provided a good and reproducible recovery. All results were within the acceptance criteria of the latest US FDA guidance and EMA guidelines. In addition, the method was successfully applied to measure plasma concentrations of gemcitabine in a patient after administration of a microdose of gemcitabine. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Effect of switching to risperidone after unsuccessful treatment with aripiprazole on plasma monoamine metabolites level in the treatment of acute schizophrenia.

    Science.gov (United States)

    Miura, Itaru; Takeuchi, Satoshi; Katsumi, Akihiko; Kanno, Keiko; Watanabe, Kenya; Mashiko, Hirobumi; Niwa, Shin-Ichi

    2012-09-01

    In the treatment of acute schizophrenia, risperidone and aripiprazole are both placed the first line antipsychotics. These two antipsychotics have different pharmacological effects. We investigated the effects of risperidone on plasma levels of homovanillic acid (HVA) and 3-methoxy-4hydroxyphenylglycol after unsuccessful aripiprazole treatment in acute schizophrenia. Ten Japanese patients with acute schizophrenia were enrolled to this study. Plasma levels of monoamine metabolites were analyzed with high-performance liquid chromatography with electrochemical detection. Risperidone improved the symptoms and 4 of 10 patients were responders. Risperidone showed a tendency to decrease plasma HVA (pHVA) levels in responders (p = 0.068), but not in non-responders (p = 1.0). At baseline, pHVA levels of responders were significantly higher than that of non-responders (p = 0.033). A trend for negative correlation was found between pHVA at baseline and the changes in Positive and Negative Syndrome Scale-Total (p = 0.061, r = -0.61). Our results suggest that high pHVA level before switching may predict good response to the second line antipsychotics after unsuccessful first antipsychotic treatment. If aripiprazole is not effective in acute schizophrenia, switching to risperidone may be effective and reasonable strategy for improving symptoms. Copyright © 2012 John Wiley & Sons, Ltd.

  4. Simultaneous separation and determination of six arsenic species in rice by anion-exchange chromatography with inductively coupled plasma mass spectrometry.

    Science.gov (United States)

    Ma, Li; Yang, Zhaoguang; Tang, Jie; Wang, Lin

    2016-06-01

    The simultaneous separation and determination of arsenite As(III), arsenate As(V), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), arsenobetaine (AsB), and arsenocholine (AsC) in rice samples have been carried out in one single anion-exchange column run by high-performance liquid chromatography with inductively coupled plasma mass spectrometry. To estimate the effect of variables on arsenic (As) speciation, the chromatographic conditions including type of competing anion, ionic strength, pH of elution buffer, and flow rate of mobile phase have been investigated by a univariate approach. Under the optimum chromatographic conditions, baseline separation of six As species has been achieved within 10 min by gradient elution program using 4 mM NH4 HCO3 at pH 8.6 as mobile phase A and 4 mM NH4 HCO3 , 40 mM NH4 NO3 at pH 8.6 as mobile phase B. The method detection limits for As(III), As(V), MMA, DMA, AsB, and AsC were 0.4, 0.9, 0.2, 0.4, 0.5, and 0.3 μg/kg, respectively. The proposed method has been applied to separation and quantification of As species in real rice samples collected from Hunan Province, China. The main As species detected in all samples were As(III), As(V) and DMA, with inorganic As accounting for over 80% of total As in these samples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. A restricted access material for rapid analysis of [11C]-labeled radiopharmaceuticals and their metabolites in plasma

    International Nuclear Information System (INIS)

    Gillings, Nic

    2009-01-01

    Introduction: Analysis of the radioactive components in plasma taken during positron emission tomography (PET) measurements is often vital for the correct quantification of the PET data. The described high-performance liquid chromatography (HPLC) method has been developed to provide a fast, sensitive and robust method for the measurement of plasma samples from PET studies using [ 11 C]-labeled radiopharmaceuticals. Methods: Unadulterated plasma samples were analyzed directly, following a simple filtration, by the use of a small extraction column, containing a restricted access material, combined with a monolithic analysis column in a column-switching HPLC system. Results: Up to 4 ml of plasma was analyzed by this method within 4.5-7 min in a fully automated process. Because of the rapid analysis, a large number of samples could be analyzed during a 90-min PET scan. The extraction column could be used for analysis of up to 500 ml of plasma before replacement was required. Conclusions: The described method is fast and robust and the large sample volumes allow for accurate determination of the radioactive components in plasma even at 90 min after injection of a [ 11 C]-labeled radiopharmaceutical.

  6. Total and inorganic arsenic in fish samples from Norwegian waters.

    Science.gov (United States)

    Julshamn, Kaare; Nilsen, Bente M; Frantzen, Sylvia; Valdersnes, Stig; Maage, Amund; Nedreaas, Kjell; Sloth, Jens J

    2012-01-01

    The contents of total arsenic and inorganic arsenic were determined in fillet samples of Northeast Artic cod, herring, mackerel, Greenland halibut, tusk, saithe and Atlantic halibut. In total, 923 individual fish samples were analysed. The fish were mostly caught in the open sea off the coast of Norway, from 40 positions. The determination of total arsenic was carried out by inductively coupled plasma mass spectrometry following microwave-assisted wet digestion. The determination of inorganic arsenic was carried out by high-performance liquid chromatography-ICP-MS following microwave-assisted dissolution of the samples. The concentrations found for total arsenic varied greatly between fish species, and ranged from 0.3 to 110 mg kg(-1) wet weight. For inorganic arsenic, the concentrations found were very low (fish used in the recent EFSA opinion on arsenic in food.

  7. Simultaneous determination of borneol and its metabolite in rat plasma by GC–MS and its application to pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Xiu-Man Sun

    2014-10-01

    Full Text Available A gas chromatography mass spectrometry (GC–MS method has been developed and fully validated for the simultaneous determination of natural borneol (NB and its metabolite, camphor, in rat plasma. Following a single liquid–liquid extraction, the analytes were separated using an HP-5MS capillary column (0.25 mm×30 m×0.25 μm and analyzed by MS in the selected ion monitoring mode. Selected ion monitor (m/z of borneol, camphor and internal standard was 95, 95 and 128, respectively. Linearity, accuracy, precision and extraction recovery of the analytes were all satisfactory. The method was successfully applied to pharmacokinetic studies of NB after oral administration to Wistar rats. Keywords: Borneol, Camphor, Simultaneous determination, Pharmacokinetics, GC–MS

  8. Rapid sensitive validated UPLC–MS method for determination of venlafaxine and its metabolite in rat plasma: Application to pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Dubey

    2013-12-01

    Full Text Available A new ultra-performance liquid chromatography–electrospray ionization mass spectrometry (UPLC–MS/ESI method for simultaneous determination of venlafaxine (VEN and its metabolite O-desmethylvenlafaxine (ODV in rat plasma has been developed and validated using Venlafaxine d6 as the internal standard. The compounds and internal standard were extracted from plasma by solid phase extraction. The UPLC separation of the analytes was performed on ACQUITY UPLC® BEH Shield RP18 (1.7 µm, 100 mm×2.1 mm column, using isocratic elution with mobile phase constituted of water (containing 2 mM ammonium acetate: acetonitrile (20:80, v/v at a flow rate of 0.3 mL/min. All of the analytes were eluted within 1.5 min. The compounds were ionized in the electrospray ionization (ESI ion source of the mass spectrometer, operating in multiple reaction monitoring (MRM and positive ion mode. The precursor to product ion transitions monitored for VEN, ODV and Venlafaxine d6 were m/z 278.3→121.08, 264.2→107.1 and 284.4→121.0, respectively. The developed and validated method was used for the pharmacokinetic study of VEN in rats. Keywords: Venlafaxine, O-desmethylvenlafaxine, Metabolite, UPLC–MS/ES

  9. A proton NMR study of the effect of Mucuna pruriens on seminal plasma metabolites of infertile males.

    Science.gov (United States)

    Gupta, Ashish; Mahdi, Abbas Ali; Ahmad, Mohammad Kaleem; Shukla, Kamla Kant; Bansal, Navneeta; Jaiswer, Shyam Pyari; Shankhwar, Satya Narain

    2011-07-15

    The objective of this study was to employ proton nuclear magnetic resonance ((1)H NMR) spectroscopy to evaluate the impact of Mucuna pruriens seeds on the metabolic profile of seminal plasma of infertile patients. A total of 180 infertile patients were administered M. pruriens seed powder for a period of three months. Age-matched healthy men comprised the control (n=50) group in the study. Lactate, alanine, choline, citrate, glycerophosphocholine (GPC), glutamine, tyrosine, histidine, phenylalanine, and uridine were measured in seminal plasma by (1)H NMR spectroscopy. To evaluate the degree of infertility and extent of hormonal imbalance induced by this milieu, separate sperm concentration, motility, lipid peroxide in seminal plasma and LH, FSH, T, and PRL hormone concentration in serum were measured using standard laboratory methods and RIA, respectively, in the same subjects. M. pruriens therapy rectifies the perturbed alanine, citrate, GPC, histidine and phenylalanine content in seminal plasma and improves the semen quality of post-treated infertile men with compared to pre-treated. Concomitantly, clinical variables in seminal plasma and blood serum were also improved over post therapy in infertile men. On the basis of these observations, it may be proposed that M. pruriens seed powder not only reactivates the enzymatic activity of metabolic pathways and energy metabolism but also rejuvenates the harmonic balance of male reproductive hormones in infertile men. These findings open more opportunities for infertility treatment and management by improving semen quality. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Molecular processes in cellular arsenic metabolism

    International Nuclear Information System (INIS)

    Thomas, David J.

    2007-01-01

    Elucidating molecular processes that underlie accumulation, metabolism and binding of iAs and its methylated metabolites provides a basis for understanding the modes of action by which iAs acts as a toxin and a carcinogen. One approach to this problem is to construct a conceptual model that incorporates available information on molecular processes involved in the influx, metabolism, binding and efflux of arsenicals in cells. This conceptual model is initially conceived as a non-quantitative representation of critical molecular processes that can be used as a framework for experimental design and prediction. However, with refinement and incorporation of additional data, the conceptual model can be expressed in mathematical terms and should be useful for quantitative estimates of the kinetic and dynamic behavior of iAs and its methylated metabolites in cells. Development of a quantitative model will be facilitated by the availability of tools and techniques to manipulate molecular processes underlying transport of arsenicals across cell membranes or expression and activity of enzymes involved in methylation of arsenicals. This model of cellular metabolism might be integrated into more complex pharmacokinetic models for systemic metabolism of iAs and its methylated metabolites. It may also be useful in development of biologically based dose-response models describing the toxic and carcinogenic actions of arsenicals

  11. Optimization and validation of bioanalytical SPE – HPLC method for the simultaneous determination of carbamazepine and its main metabolite, carbamazepine-10, 11-epoxide, in plasma

    Directory of Open Access Journals (Sweden)

    Jasmina Tonic – Ribarska

    2012-03-01

    Full Text Available Carbamazepine is widely used as an antiepileptic drug in the treatment of partial and generalized tonic-clonic seizures. Carbamazepine 10,11-epoxide is the most important metabolite of carbamazepine, because it is a pharmacologically active compound with anticonvulsant properties. According to that, the routine analysis of carbamazepine 10,11-epoxide along with carbamazepine may provide optimal therapeutic monitoring of carbamazepine treatment. The aim of this study was to optimize and validate a simple and reliable solid - phase extraction method followed by RP-HPLC for the simultaneous determination of plasma levels of carbamazepine and carbamazepine-10,11-epoxide, in order to assure the implementation of the method for therapeutic monitoring. The extraction of the analytes from the plasma samples was performed by means of a solid-phase extraction procedure. The separation was carried out on a reversed-phase column using isocratic elution with acetonitrile and water (35:65, v/v as a mobile phase. The temperature was 30°C and UV detection was set at 220 nm. The extraction yield values were more than 98% for all analytes, measured at four concentration levels of the linear concentration range. The method displayed excellent selectivity, sensitivity, linearity, precision and accuracy. Stability studies indicate that stock solutions and plasma samples were stabile under different storage conditions at least during the observed period. The method was successfully applied to determine the carbamazepine and carbamazepine-10,11-epoxide in plasma of epileptic patients treated with carbamazepine as monotherapy and in polytherapy. In conclusion, the proposed method is suitable for application in therapeutic drug monitoring of epileptic patients undergoing treatment with carbamazepine.

  12. Diets high in resistant starch increase plasma levels of trimethylamine-N-oxide, a gut microbiome metabolite associated with CVD risk

    Energy Technology Data Exchange (ETDEWEB)

    Bergeron, Nathalie; Williams, Paul T.; Lamendella, Regina; Faghihnia, Nastaran; Grube, Alyssa; Li, Xinmin; Wang, Zeneng; Knight, Rob; Jansson, Janet K.; Hazen, Stanley L.; Krauss, Ronald M.

    2016-12-20

    Production of trimethylamine-N-oxide (TMAO), a biomarker of CVD risk, is dependent on intestinal microbiota, but little is known of dietary conditions promoting changes in gut microbial communities. Resistant starches (RS) alter the human microbiota. We sought to determine whether diets varying in RS and carbohydrate (CHO) content affect plasma TMAO levels. We also assessed postprandial glucose and insulin responses and plasma lipid changes to diets high and low in RS. In a cross-over trial, fifty-two men and women consumed a 2-week baseline diet (41 percentage of energy (%E) CHO, 40 % fat, 19 % protein), followed by 2-week high- and low-RS diets separated by 2-week washouts. RS diets were assigned at random within the context of higher (51–53 %E)v. lower CHO (39–40 %E) intake. Measurements were obtained in the fasting state and, for glucose and insulin, during a meal test matching the composition of the assigned diet. With lower CHO intake, plasma TMAO, carnitine, betaine andγ-butyrobetaine concentrations were higher after the high-v. low-RS diet (P<0·01 each). These metabolites were not differentially affected by highv. low RS when CHO intake was high. Although the high-RS meal reduced postprandial insulin and glucose responses when CHO intake was low (P<0·01 each), RS did not affect fasting lipids, lipoproteins, glucose or insulin irrespective of dietary CHO content. In conclusion, a lower-CHO diet high in RS was associated with higher plasma TMAO levels. These findings, together with the absence of change in fasting lipids, suggest that short-term high-RS diets do not improve markers of cardiometabolic health.

  13. Liquid chromatography-tandem mass spectrometric assay for the simultaneous determination of the irreversible BTK inhibitor ibrutinib and its dihydrodiol-metabolite in plasma and its application in mouse pharmacokinetic studies

    NARCIS (Netherlands)

    Rood, Johannes J M; van Hoppe, Stephanie; Schinkel, Alfred H.; Schellens, Jan H M; Beijnen, Jos H.; Sparidans, Rolf W.

    2016-01-01

    A validated simple, fast and sensitive bio-analytical assay for ibrutinib and its dihydrodiol metabolite in human and mouse plasma was set up. Sample preparation was performed by protein precipitation, and addition of the respective deuterated internal standards, followed by LC-MS/MS analysis.

  14. Unbiased Scanning Method and Data Banking Approach Using Ultra-High Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry for Quantitative Comparison of Metabolite Exposure in Plasma across Species Analyzed at Different Dates.

    Science.gov (United States)

    Gao, Hongying; Deng, Shibing; Obach, R Scott

    2015-12-01

    An unbiased scanning methodology using ultra high-performance liquid chromatography coupled with high-resolution mass spectrometry was used to bank data and plasma samples for comparing the data generated at different dates. This method was applied to bank the data generated earlier in animal samples and then to compare the exposure to metabolites in animal versus human for safety assessment. With neither authentic standards nor prior knowledge of the identities and structures of metabolites, full scans for precursor ions and all ion fragments (AIF) were employed with a generic gradient LC method to analyze plasma samples at positive and negative polarity, respectively. In a total of 22 tested drugs and metabolites, 21 analytes were detected using this unbiased scanning method except that naproxen was not detected due to low sensitivity at negative polarity and interference at positive polarity; and 4'- or 5-hydroxy diclofenac was not separated by a generic UPLC method. Statistical analysis of the peak area ratios of the analytes versus the internal standard in five repetitive analyses over approximately 1 year demonstrated that the analysis variation was significantly different from sample instability. The confidence limits for comparing the exposure using peak area ratio of metabolites in animal plasma versus human plasma measured over approximately 1 year apart were comparable to the analysis undertaken side by side on the same days. These statistical analysis results showed it was feasible to compare data generated at different dates with neither authentic standards nor prior knowledge of the analytes.

  15. A restricted access material for rapid analysis of [(11)C]-labeled radiopharmaceuticals and their metabolites in plasma

    DEFF Research Database (Denmark)

    Gillings, N.

    2009-01-01

    , combined with a monolithic analysis column in a column-switching HPLC system. RESULTS: Up to 4 ml of plasma was analyzed by this method within 4.5-7 min in a fully automated process. Because of the rapid analysis, a large number of samples could be analyzed during a 90-min PET scan. The extraction column...

  16. Plasma amino acid and metabolite signatures tracking diabetes progression in the UCD-T2DM rat model

    Science.gov (United States)

    Elevations of plasma concentrations of branched-chain amino acids (BCAAs) are observed in human insulin resistance and type 2 diabetes mellitus (T2DM); however, there has been some controversy with respect to the passive or causative nature of the BCAA phenotype. Using untargeted metabolomics, plasm...

  17. Quantitative determination of regorafenib and its two major metabolites in human plasma with high-performance liquid chromatography and ultraviolet detection.

    Science.gov (United States)

    Fujita, Kazuma; Miura, Masatomo; Shibata, Hiroyuki

    2016-10-01

    A simple, highly sensitive and specific high-performance liquid chromatography (HPLC) method was developed for the simultaneous quantitation of regorafenib, N-oxidemetabolite (M-2) and the desmethyl N-oxide metabolite (M-5) in human plasma. Regorafenib, M-2, M-5 and the internal standard sorafenib were separated using a mobile phase of 0.5% KH2 PO4 (pH 3.5)-acetonitrile (30:70, v/v), on a Capcell PAK MG II column at a flow rate of 0.5 mL/min and measurement at UV 260 nm. The lower limits of quantification for regorafenib, M-2 and M-5 were 10 ng/mL for each analyte. A procedure using solid-phase extraction required only a small amount of plasma (100 μL) for one analysis while providing high extraction recovery (>81% for all compounds) and good selectivity. Coefficients of variation for intra- and inter-day assays were HPLC assay is suitable for clinical pharmacokinetic studies of regorafenib. The present HPLC method is currently in use for our observational studies of patients under treatment. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Simultaneous determination of 7-O-succinyl macrolactin A and its active major metabolite, macrolactin A in dog plasma using high-performance liquid chromatography with UV detection.

    Science.gov (United States)

    Kim, Eunyoung; Shin, Beomsoo; Kwon, Kwang-il; Bang, Joon Seok; Kang, Wonku

    2014-10-01

    We developed a method for the simultaneous quantification of 7-O-succinyl macrolactin A and its active metabolite, macrolactin A, in dog plasma. After protein precipitation with acetonitrile including flufenamic acid as an internal standard, 7-O-succinyl macrolactin A, macrolactin A, and flufenamic acid were chromatographed on a reverse-phase C18 analytical column. The mobile phase, consisting of 20 mM acetate buffer and acetonitrile, was eluted using a gradient program at 1 mL/min, and the UV absorbance was measured at 230 nm. The retention times of 7-O-succinyl macrolactin A, flufenamic acid, and macrolactin A were 3.4, 4.8, and 6.9 min, respectively. The coefficient of variation in the assay precision for both substances was less than 6%, and the accuracy ranged from 96 to 105%. This method was used to measure the concentrations of 7-O-succinyl macrolactin A and macrolactin A in dog plasma following an intravenous administration of a single dose (25 mg/kg) of 7-O-succinyl macrolactin A salt. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Simultaneous determination of praziquantel, pyrantel embonate, febantel and its active metabolites, oxfendazole and fenbendazole, in dog plasma by liquid chromatography/mass spectrometry.

    Science.gov (United States)

    Klausz, Gabriella; Keller, Éva; Sára, Zoltán; Székely-Körmöczy, Péter; Laczay, Péter; Ary, Kornélia; Sótonyi, Péter; Róna, Kálmán

    2015-12-01

    A liquid chromatography-electrospray-mass spectrometry method (LC/MS) has been developed and validated for determination of praziquantel (PZQ), pyrantel (PYR), febantel (FBT), and the active metabolites fenbendazole (FEN) and oxfendazole (OXF), in dog plasma, using mebendazole as internal standard (IS). The method consists of solid-phase extractions on Strata-X polymeric cartridges. Chromatographic separation was carried out on a Phenomenex Gemini C6 -Phenyl column using binary gradient elution containing methanol and 50 mm ammonium-formate (pH 3). The method was linear (r(2)  ≥ 0.990) over concentration ranges of 3-250 ng/mL for PYR andFEB, 5-250 ng/mL for OXF and FEN, and 24-1000 ng/mL for PZQ. The mean precisions were 1.3-10.6% (within-run) and 2.5-9.1% (between-run), and mean accuracies were 90.7-109.4% (within-run) and 91.6-108.2% (between-run). The relative standard deviations (RSD) were <9.1%. The mean recoveries of five targeted compounds from dog plasma ranged from 77 to 94%.The new LC/MS method described herein was fully validated and successfully applied to the bioequivalence studies of different anthelmintic formulations such as tablets containing PZQ, PYR embonate and FBT in dogs after oral administration. Copyright © 2015 John Wiley & Sons, Ltd.

  20. A biological indicator of inorganic arsenic exposure using the sum of urinary inorganic arsenic and monomethylarsonic acid concentrations

    Science.gov (United States)

    Hata, Akihisa; Kurosawa, Hidetoshi; Endo, Yoko; Yamanaka, Kenzo; Fujitani, Noboru; Endo, Ginji

    2016-01-01

    Objectives: The sum of urinary inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) concentrations is used for the biological monitoring of occupational iAs exposure. Although DMA is a major metabolite of iAs, it is an inadequate index because high DMA levels are present in urine after seafood consumption. We estimated the urinary iAs+MMA concentration corresponding to iAs exposure. Methods: We used data from two arsenic speciation analyses of urine samples from 330 Bangladeshi with oral iAs exposure and 172 Japanese workers without occupational iAs exposure using high-performance liquid chromatography with inductively coupled plasma mass spectrometry. Results: iAs, MMA, and DMA, but not arsenobetaine (AsBe), were detected in the urine of the Bangladeshi subjects. The correlation between iAs+MMA+DMA and iAs+MMA was obtained as log (iAs+MMA) = 1.038 log (iAs+MMA+DMA) -0.658. Using the regression formula, the iAs+MMA value was calculated as 2.15 and 7.5 μg As/l, corresponding to 3 and 10 μg As/m3 of exposures, respectively. In the urine of the Japanese workers, arsenic was mostly excreted as AsBe. We used the 95th percentile of iAs+MMA (12.6 μg As/l) as the background value. The sum of the calculated and background values can be used as a biological indicator of iAs exposure. Conclusion: We propose 14.8 and 20.1 μg As/l of urinary iAs+MMA as the biological indicators of 3 and 10 μg As/m3 iAs exposure, respectively. PMID:27010090

  1. Biomarkers of Exposure: A Case Study with Inorganic Arsenic

    OpenAIRE

    Hughes, Michael F.

    2006-01-01

    The environmental contaminant inorganic arsenic (iAs) is a human toxicant and carcinogen. Most mammals metabolize iAs by reducing it to trivalency, followed by oxidative methylation to pentavalency. iAs and its methylated metabolites are primarily excreted in urine within 4–5 days by most species and have a relatively low rate of bioaccumulation. Intra- and interindividual differences in the methylation of iAs may affect the adverse health effects of arsenic. Both inorganic and organic trival...

  2. Methods of analysis by the U.S. Geological Survey National Water Quality Laboratory; determination of whole-water recoverable arsenic, boron, and vanadium using inductively coupled plasma-mass spectrometry

    Science.gov (United States)

    Garbarino, John R.

    2000-01-01

    Analysis of in-bottle digestate by using the inductively coupled plasma?mass spectrometric (ICP?MS) method has been expanded to include arsenic, boron, and vanadium. Whole-water samples are digested by using either the hydrochloric acid in-bottle digestion procedure or the nitric acid in-bottle digestion procedure. When the hydrochloric acid in-bottle digestion procedure is used, chloride must be removed from the digestate by subboiling evaporation before arsenic and vanadium can be accurately determined. Method detection limits for these elements are now 10 to 100 times lower than U.S. Geological Survey (USGS) methods using hydride generation? atomic absorption spectrophotometry (HG? AAS) and inductively coupled plasma? atomic emission spectrometry (ICP?AES), thus providing lower variability at ambient concentrations. The bias and variability of the methods were determined by using results from spike recoveries, standard reference materials, and validation samples. Spike recoveries in reagent-water, surface-water, ground-water, and whole-water recoverable matrices averaged 90 percent for seven replicates; spike recoveries were biased from 25 to 35 percent low for the ground-water matrix because of the abnormally high iron concentration. Results for reference material were within one standard deviation of the most probable value. There was no significant difference between the results from ICP?MS and HG?AAS or ICP?AES methods for the natural whole-water samples that were analyzed.

  3. [11C]-Flumazenil metabolites: Measurements of unchanged ligand in plasma using thin layer chromatography and rapid liquid chromatography

    International Nuclear Information System (INIS)

    Loc'h, C.; Hantraye, Ph.; Khalili-Varasteh, M.; Maziere, B.; Delforge, J.; Brouillet, E.; Syrota, A.; Maziere, M.

    1990-01-01

    To study in vivo benzodiazepine (BZ) receptors using PET, Flumazenil, an imidazobenzodiazepine with selective antagonistic actions, has been labeled with 11 C on its methyl group. The accurate determination of in vivo binding parameters using biomathematical models requires the knowledge of radioligand metabolism and the measurement of the plasmatic concentration of unchanged radioligand is mandatory. The present report describes and compares rapid and simple analytical procedures to measure unchanged [ 11 C]-Flumazenil in plasma

  4. Bioanalysis of a panel of neurotransmitters and their metabolites in plasma samples obtained from pediatric patients with neuroblastoma and Wilms' tumor.

    Science.gov (United States)

    Konieczna, Lucyna; Roszkowska, Anna; Stachowicz-Stencel, Teresa; Synakiewicz, Anna; Bączek, Tomasz

    2018-02-01

    This paper details the quantitative analysis of neurotransmitters, including dopamine (DA), norepinephrine (NE), epinephrine (E), and serotonin (5-HT), along with their respective precursors and metabolites in children with solid tumors: Wilms' tumor (WT) and neuroblastoma (NB). A panel of neurotransmitters was determined with the use of dispersive liquid-liquid microextraction (DLLME) technique combined with liquid-chromatography mass spectrometry (LC-MS/MS) in plasma samples obtained from a group of pediatric subjects with solid tumors and a control group of healthy children. Next, statistical univariate analysis (t-test) and multivariate analysis (Principal Component Analysis) were performed using chromatographic data. The levels of tyrosine (Tyr) and tryptophan (Trp) (the precursors of analyzed neurotransmitters) as well as 3,4-dihydroxyphenylacetic acid (DOPAC) (a product of metabolism of DA) were significantly higher in the plasma samples obtained from pediatric patients with WT than in the samples taken from the control group. Moreover, statistically significant differences were observed between the levels of 5-HT and homovanillic acid (HVA) in the plasma samples from pediatric patients with solid tumors and the control group. However, elevated levels of these analytes did not facilitate a clear distinction between pediatric patients with WT and those with NB. Nonetheless, the application of advanced statistical tools allowed the healthy controls to be differentiated from the pediatric oncological patients. The identification and quantification of a panel of neurotransmitters as potential prognostic factors in selected childhood malignancies may provide clinically relevant information about ongoing metabolic alterations, and it could potentially serve as an adjunctive strategy in the effective diagnosis and treatment of solid tumors in children. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. A sensitive, simple and rapid HPLC–MS/MS method for simultaneous quantification of buprenorpine and its N-dealkylated metabolite norbuprenorphine in human plasma

    Directory of Open Access Journals (Sweden)

    Yi-Ya Wang

    2013-08-01

    Full Text Available A sensitive, simple and rapid high performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS method was developed and fully validated for the simultaneous quantification of buprenorphine (BUP and its N-dealkylated metabolite norbuprenorphine (NBUP in 200μL human plasma. Human plasma samples were prepared using liquid–liquid extraction, and then separated on a Shiseido MG C18 (5μm, 2.0mm×50mm via 4.1min gradient elution. Following electrospray ionization, the analytes were quantified on a triple–quadrupole mass spectrometer in multiple-reaction-monitoring (MRM positive ion mode. Linearity was achieved from 25.0 to 10000pg/mL for buprenorphine, from 20.0 to 8000pg/mL for norbuprenorphine with r2>0.99. The method was demonstrated with acceptable accuracy, precision and specificity for the detection of buprenorphine and norbuprenorphine. Recovery was 81.8–88.8% for buprenorphine and 77.0–84.6% for norbuprenorphine, and the matrix effect was 95.6–97.4% for buprenorphine and 94.0–96.9% for norbuprenorphine; all were not concentration dependent. With validated matrix and autosampler stability data, this method was successfully applied in a bioequivalence study to support abbreviated new drug application. Keywords: Buprenorphine, Norbuprenorphine, Human plasma, HPLC–MS/MS

  6. Characterisation of the appearance of radioactive metabolites in monkey and human plasma from the 5-HT1A receptor radioligand, [carbonyl-11C]WAY-100635 - explanation of high signal contrast in PET and an aid to biomathematical modelling

    International Nuclear Information System (INIS)

    Osman, Safiye; Lundkvist, Camilla; Pike, Victor W.; Halldin, Christer; McCarron, Julie A.; Swahn, Carl-Gunnar; Farde, Lars; Ginovart, Nathalie; Luthra, Sajinder K.; Gunn, Roger N.; Bench, Christopher J.; Sargent, Peter A.; Grasby, Paul M.

    1998-01-01

    N-(2-(4-(2-Methoxy-phenyl)-1-piperazin-1-yl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide (WAY-100635), labelled in its amido carbonyl group with 11 C (t 1/2 = 20.4 min), is a promising radioligand for the study of brain 5-HT 1A receptors with positron emission tomography (PET). Thus, in PET experiments in six cynomolgus monkeys and seven healthy male volunteers, [carbonyl- 11 C]WAY-100635 was taken up avidly by brain. Radioactivity was retained in regions rich in 5-HT 1A receptors, such as occipital cortex, temporal cortex and raphe nuclei, but cleared rapidly from cerebellum, a region almost devoid of 5-HT 1A receptors. [Carbonyl- 11 C]WAY-100635 provides about 3- and 10-fold higher signal contrast (receptor-specific to nonspecific binding) than [O-methyl- 11 C]WAY-100635 in receptor-rich areas of monkey and human brain, respectively. To elucidate the effect of label position on radioligand behaviour and to aid in the future biomathematical interpretation of the kinetics of regional cerebral radioactivity uptake in terms of receptor-binding parameters, HPLC was used to measure [carbonyl- 11 C]WAY-100635 and its radioactive metabolites in plasma at various times after intravenous injection. Radioactivity cleared rapidly from monkey and human plasma. Parent radioligand represented 19% of the radioactivity in monkey plasma at 47 min and 8% of the radioactivity in human plasma at 40 min. [Carbonyl- 11 C]desmethyl-WAY-100635 was below detectable limits in monkey plasma and at most a very minor radioactive metabolite in human plasma. [ 11 C]Cyclohexanecarboxylic acid was identified as a significant radioactive metabolite. In human plasma this maximally represented 21% of the radioactivity at 10 min after radioligand injection. All other major radioactive metabolites in monkey and human plasma were even more polar. No-carrier-added [carbonyl- 11 C]cyclohexanecarboxylic acid was prepared in the laboratory and after intravenous administration into cynomolgus monkey was

  7. Arsenic compounds in a marine food chain

    Energy Technology Data Exchange (ETDEWEB)

    Goessler, W.; Irgolic, K.J.; Kuehnelt, D.; Schlagenhaufen, C. [Institute for Analytical Chemistry, Karl-Franzens-Universitaet Graz, Universitaetsplatz 1, A-8010 Graz (Austria); Maher, W. [CRC for Freshwater Ecology, University of Canberra, PO Box 1, Belconnen ACT. 2616 (Australia); Kaise, T. [Laboratory of Environmental Chemistry, School of Life Science, University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachijoji, Tokyo 192-03 (Japan)

    1997-10-01

    A three-organism food chain within a rock pool at Rosedale, NSW, Australia, was investigated with respect to arsenic compounds by high performance liquid chromatography - hydraulic high pressure nebulization - inductively coupled plasma mass spectrometry (HPLC-HHPN-ICP-MS). Total arsenic concentration was determined in the seaweed Hormosira banksii (27.2 {mu}g/g dry mass), in the gastropod Austrocochlea constricta (74.4 {mu}g/g dry mass), which consumes the seaweed, and in the gastropod Morula marginalba (233 {mu}g/g dry mass), which eats Austrocochlea constricta. The major arsenic compounds in the seaweed were (2`R)-dimethyl[1-O-(2`,3`-dihydroxypropyl)-5-deoxy-{beta}-d-ribofuranos-5-yl]arsine oxide and an unidentified compound. The herbivorous gastropod Austrocochlea constricta transformed most of the arsenic taken up with the seaweed to arsenobetaine. Traces of arsenite, arsenate, dimethylarsinic acid, arsenocholine, the tetramethylarsonium cation, and several unknown arsenic compounds were detected. Arsenobetaine accounted for 95% of the arsenic in the carnivorous gastropod Morula marginalba. In Morula marginalba the concentration of arsenocholine was higher, and the concentrations of the minor arsenic compounds lower than in the herbivorous gastropod Austrocochlea constricta. (orig.) With 4 figs., 1 tab., 13 refs.

  8. A single LC-tandem mass spectrometry method for the simultaneous determination of 14 antimalarial drugs and their metabolites in human plasma.

    Science.gov (United States)

    Hodel, E M; Zanolari, B; Mercier, T; Biollaz, J; Keiser, J; Olliaro, P; Genton, B; Decosterd, L A

    2009-04-01

    Among the various determinants of treatment response, the achievement of sufficient blood levels is essential for curing malaria. For helping us at improving our current understanding of antimalarial drugs pharmacokinetics, efficacy and toxicity, we have developed a liquid chromatography-tandem mass spectrometry method (LC-MS/MS) requiring 200mul of plasma for the simultaneous determination of 14 antimalarial drugs and their metabolites which are the components of the current first-line combination treatments for malaria (artemether, artesunate, dihydroartemisinin, amodiaquine, N-desethyl-amodiaquine, lumefantrine, desbutyl-lumefantrine, piperaquine, pyronaridine, mefloquine, chloroquine, quinine, pyrimethamine and sulfadoxine). Plasma is purified by a combination of protein precipitation, evaporation and reconstitution in methanol/ammonium formate 20mM (pH 4.0) 1:1. Reverse-phase chromatographic separation of antimalarial drugs is obtained using a gradient elution of 20mM ammonium formate and acetonitrile both containing 0.5% formic acid, followed by rinsing and re-equilibration to the initial solvent composition up to 21min. Analyte quantification, using matrix-matched calibration samples, is performed by electro-spray ionization-triple quadrupole mass spectrometry by selected reaction monitoring detection in the positive mode. The method was validated according to FDA recommendations, including assessment of extraction yield, matrix effect variability, overall process efficiency, standard addition experiments as well as antimalarials short- and long-term stability in plasma. The reactivity of endoperoxide-containing antimalarials in the presence of hemolysis was tested both in vitro and on malaria patients samples. With this method, signal intensity of artemisinin decreased by about 20% in the presence of 0.2% hemolysed red-blood cells in plasma, whereas its derivatives were essentially not affected. The method is precise (inter-day CV%: 3.1-12.6%) and sensitive

  9. Arsenic drinking water exposure and urinary excretion among adults in the Yaqui Valley, Sonora, Mexico

    International Nuclear Information System (INIS)

    Meza, M.M.; Kopplin, M.J.; Burgess, J.L.; Gandolfi, A.J.

    2004-01-01

    The objective of this study was to determine arsenic exposure via drinking water and to characterize urinary arsenic excretion among adults in the Yaqui Valley, Sonora, Mexico. A cross-sectional study was conducted from July 2001 to May 2002. Study subjects were from the Yaqui Valley, Sonora, Mexico, residents of four towns with different arsenic concentrations in their drinking water. Arsenic exposure was estimated through water intake over 24 h. Arsenic excretion was assessed in the first morning void urine. Total arsenic concentrations and their species arsenate (As V), arsenite (As III), monomethyl arsenic (MMA), and dimethyl arsenic (DMA) were determined by HPLC/ICP-MS. The town of Esperanza with the highest arsenic concentration in water had the highest daily mean intake of arsenic through drinking water, the mean value was 65.5 μg/day. Positive correlation between total arsenic intake by drinking water/day and the total arsenic concentration in urine (r=0.50, P<0.001) was found. Arsenic excreted in urine ranged from 18.9 to 93.8 μg/L. The people from Esperanza had the highest geometric mean value of arsenic in urine, 65.1 μg/L, and it was statistically significantly different from those of the other towns (P<0.005). DMA was the major arsenic species in urine (47.7-67.1%), followed by inorganic arsenic (16.4-25.4%), and MMA (7.5-15%). In comparison with other reports the DMA and MMA distribution was low, 47.7-55.6% and 7.5-9.7%, respectively, in the urine from the Yaqui Valley population (except the town of Cocorit). The difference in the proportion of urinary arsenic metabolites in those towns may be due to genetic polymorphisms in the As methylating enzymes of these populations

  10. Arsenic drinking water exposure and urinary excretion among adults in the Yaqui Valley, Sonora, Mexico.

    Science.gov (United States)

    Meza, Maria Mercedes; Kopplin, Michael J; Burgess, Jefferey L; Gandolfi, A Jay

    2004-10-01

    The objective of this study was to determine arsenic exposure via drinking water and to characterize urinary arsenic excretion among adults in the Yaqui Valley, Sonora, Mexico. A cross-sectional study was conducted from July 2001 to May 2002. Study subjects were from the Yaqui Valley, Sonora, Mexico, residents of four towns with different arsenic concentrations in their drinking water. Arsenic exposure was estimated through water intake over 24 h. Arsenic excretion was assessed in the first morning void urine. Total arsenic concentrations and their species arsenate (As V), arsenite (As III), monomethyl arsenic (MMA), and dimethyl arsenic (DMA) were determined by HPLC/ICP-MS. The town of Esperanza with the highest arsenic concentration in water had the highest daily mean intake of arsenic through drinking water, the mean value was 65.5 microg/day. Positive correlation between total arsenic intake by drinking water/day and the total arsenic concentration in urine (r = 0.50, P < 0.001) was found. Arsenic excreted in urine ranged from 18.9 to 93.8 microg/L. The people from Esperanza had the highest geometric mean value of arsenic in urine, 65.1 microg/L, and it was statistically significantly different from those of the other towns (P < 0.005). DMA was the major arsenic species in urine (47.7-67.1%), followed by inorganic arsenic (16.4-25.4%), and MMA (7.5-15%). In comparison with other reports the DMA and MMA distribution was low, 47.7-55.6% and 7.5-9.7%, respectively, in the urine from the Yaqui Valley population (except the town of Cocorit). The difference in the proportion of urinary arsenic metabolites in those towns may be due to genetic polymorphisms in the As methylating enzymes of these populations.

  11. Determination of ximelagatran, melagatran and two intermediary metabolites in plasma by mixed-mode solid phase extraction and LC-MS/MS.

    Science.gov (United States)

    Dunér, Kristina; Bäckström, Jonas; Magnell, Niklas; Svennberg, Henrik; Ahnoff, Martin; Logren, Ulrika

    2007-06-01

    An analytical method was developed for the determination of ximelagatran, an oral direct thrombin inhibitor, its active metabolite melagatran, and the two intermediate metabolites, OH-melagatran and ethyl-melagatran in human plasma. Extraction of plasma was carried out on a mixed mode bonded sorbent material (C8/SO(3)(-)). All four analytes, including their isotope-labelled internal standards, were eluted at high ionic strength with a mixture of 50% methanol and 50% buffer (0.25 M ammonium acetate and 0.05 M formic acid, pH 5.3) with an extraction recovery above 80%. The extracts were demonstrated to be clean in terms of a low concentration of albumin and lysoPC. The sample extraction was fully automated and performed in 96-well plates using a Tecan Genesis pipetting robot. Analysis of the extracts were performed with liquid chromatography followed by positive electrospray ionization mass spectrometry. The low organic content and the low pH of the extracts allowed for, after dilution 1:3 with buffer, direct injection onto the LC-column. The four analytes were separated on a C18 analytical LC-column using gradient elution with the acetonitrile concentration varying from 10 to 30% (v/v) and the ammonium acetate and acetic acid concentration kept constant at 10 and 5 mmol/L, respectively, at a flow rate of 0.75 mL/min. Linearity was achieved over the calibrated range 0.010-4.0 micromol/L with accuracy and relative standard deviation in the range 96.9-101.2% and 6.6-17.1%, respectively at LLOQ, and in the range 94.7-102.6% and 2.7-6.8%, respectively at concentrations above 3 x LLOQ. The method replaces a manual method, and displays the advantages of having a fully automated sample clean-up, no evaporation/reconstitution step, high recovery, and complete LC-separation of all four analytes.

  12. A validated LC–MS/MS method for the determination of tolterodine and its metabolite in rat plasma and application to pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Rihana Parveen Shaik

    2013-12-01

    Full Text Available Liquid chromatography–tandem mass spectrometry (LC–MS/MS method was used for simultaneous quantification of tolterodine and its metabolite 5-hydroxy methyl tolterodine in rat plasma. Tolterodine-d6 and 5-hydroxy methyl tolterodine-d14 were used as internal standards (IS. Chromatographic separation was performed on Ascentis Express RP amide (50 mm×4.6 mm, 2.7 μm column with an isocratic mobile phase composed of 10 mM ammonium acetate and acetonitrile in the ratio of 20:80 (v/v, at a flow-rate of 0.5 mL/min. Tolterodine, tolterodine-d6, 5-hydroxy methyl tolterodine and 5-hydroxy methyl tolterodine-d14 were detected with proton adducts at m/z 326.1→147.1, 332.3→153.1, 342.2→223.1 and 356.2→223.1 in multiple reaction monitoring (MRM positive mode respectively. The drug, metabolite and internal standards were extracted by liquid–liquid extraction method. The method was validated over a linear concentration range of 20.00–5000.00 pg/mL for tolterodine and 20.00–5000.00 pg/mL for 5-hydroxy methyl tolterodine. This method demonstrated intra- and inter-day precision of 0.62–6.36% and 1.73–4.84% for tolterodine, 1.38–4.22% and 1.62–4.25% for 5-hydroxy methyl tolterodine respectively. This method also demonstrated intra- and inter-day accuracy of 98.75–103.56% and 99.20–104.40% for tolterodine, 98.08–104.67% and 98.73–103.06% for 5-hydroxy methyl tolterodine respectively. Both analytes were found to be stable throughout freeze–thaw cycles, bench top and postoperative stability studies. This method was successfully applied for the pharmacokinetic analysis of rat plasma samples following i.v. administration. Keywords: LC–MS/MS, Tolterodine, 5-Hydroxy methyl tolterodine, Pharmacokinetics

  13. [Simultaneous determination of tryptophan and its metabolites in plasma by high performance liquid chromatography with on-column derivatization].

    Science.gov (United States)

    Feng, Chengya; Gao, Jieying; Zhen, Qianna; Fan, Zimian; Zhu, Mingsong; Yang, Xiangchun; Ding, Min

    2013-06-01

    A high performance liquid chromatography-ultraviolet/fluorescence detection (HPLC-UV/FLD) with on-column derivatization was established to simultaneously determine tryptophan (Trp), kynurenine (Kyn), 5-hydroxyindole acetic acid (5-Hiaa) and kynurenic acid (Kyna). A Hypersil C-18 column (250 mm x 4.0 mm, 5 microm) was used for the analysis at 30 degrees C. The separation was carried out with the mobile phase consisting of 250 mmol/L zinc acetate (pH 5.5) and acetonitrile (95: 5, v/v) at a flow rate of 0.8 mL/min using 3-nitrotyrosine as internal standard (IS). The excitation (Ex) and emission (Em) wavelengths were set at 278 nm (lambda(ex))/343 nm (lambda(em)) for 5-Hiaa and 244 nm (lambda(ex))/400 nm (lambda(em)) for Kyna, while the wavelengths of ultraviolet detection were set at 360 nm for Kyn and IS, 302 nm for Trp. The recoveries were in the range of 91.62% to 114.17%. The linearities were from 2.50 micromol/L to 320.00 micromol/L for Trp, 0.32 micromol/L to 15.36 micromol/L for Kyn, 3.27 nmol/L to 104.60 nmol/L for 5-Hiaa, and 14.00 nmol/L to 464.80 nmol/L for Kyna. The detection limits were 0.078 micromol/L, 0.056 micromol/L, 0.690 nmol/L and 1.290 nmol/L for Trp, Kyn, 5-Hiaa, and Kyna, respectively. Thirty plasma samples of normal pregnant women and 28 plasma samples of healthy controls were tested, and the results exhibited that the concentrations of Trp, Kyn and Kyna in the plasma of the normal pregnant women were significantly different from those of the control group (all P < 0.01). The method is simple and sensitive with good reproducibility, and it is suitable for clinical measurements.

  14. Survey of inorganic arsenic in marine animals and marine certified reference materials by anion exchange high-performance liquid chromatography-inductively coupled plasma mass spectrometry

    DEFF Research Database (Denmark)

    Sloth, Jens Jørgen; Larsen, Erik Huusfeldt; Julshamn, Kåre

    2005-01-01

    , bivalves, and marine mammals as well as a range of marine certified reference materials, and the results were compared to values published in the literature. For fish and marine mammals, the results were in most cases below the limit of detection. For other sample types, inorganic arsenic concentrations up...

  15. Comparative oxidation state specific analysis of arsenic species by high-performance liquid chromatography- inductively coupled plasma-mass spectrometry and hydride generation-cryotrapping-atomic absorption spectrometry

    Czech Academy of Sciences Publication Activity Database

    Currier, J. M.; Saunders, R. J.; Ding, L.; Bodnar, W.; Cable, P.; Matoušek, Tomáš; Creed, J. T.; Stýblo, M.

    2013-01-01

    Roč. 28, č. 6 (2013), s. 843-852 ISSN 0267-9477 R&D Projects: GA MŠk LH12040 Institutional support: RVO:68081715 Keywords : arsenic * speciaton analysis * As metabolism Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 3.396, year: 2013

  16. ARSENIC DETERMINATION IN SALINE WATERS UTILIZING A TUBULAR MEMBRANE AS A GAS-LIQUID SEPATRATOR FOR HYDRIDE GENERATION INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

    Science.gov (United States)

    A tubular silicone rubber membrane is evaluated as a gas-liquid separator for the determination of arsenic in saline waters via HG-ICP-MS. The system was optimized in terms of NaBH and HCI concentrations. The intermediate gas and carrier gas were optimized in terms of sensitiity ...

  17. High-performance liquid chromatography and inductively coupled plasma mass spectrometry (HPLC-ICP-MS) for the analysis of xenobiotic metabolites in rat urine: application to the metabolites of 4-bromoaniline.

    Science.gov (United States)

    Nicholson, J K; Lindon, J C; Scarfe, G; Wilson, I D; Abou-Shakra, F; Castro-Perez, J; Eaton, A; Preece, S

    2000-02-01

    The use of HPLC-ICP-MS for the profiling and quantification of the metabolites of 4-bromoaniline following reversed-phase gradient chromatography is demonstrated. In the 0-8 h post dose sample, which contained the highest concentrations of compound-related material, it was possible to detect at least 16 metabolites of the compound. The methodology described offers the possibility of obtaining metabolite profiles and quantification for drugs and other xenobiotics in biological fluids and excreta without the requirement for radiolabelled tracers.

  18. Feeding motivation and plasma metabolites in pregnant sows fed diets rich in dietary fiber either once or twice daily

    DEFF Research Database (Denmark)

    Jensen, Margit Bak; Pedersen, Lene Juul; Theil, Peter Kappel

    2012-01-01

    in an operant conditioning test, and samples of peripheral blood were taken in a balanced design, at 0900, 1200, 1900, and 0700 h, corresponding to 1, 4, 11, and 23 h after feeding for restricted sows fed once daily. No differences in the feeding motivation were found between the 4 restricted diets at any......, indicating that feeding twice daily reduced feeding motivation during the night compared with feeding once daily. Among restricted-fed sows, plasma concentrations of short-chain fatty acids (SCFA) were greater in sows fed high-fiber diets compared with the control (P = 0.02). Nonesterified fatty acid...... level of fiber in the diet of restrictedly fed sows did not reduce their feeding motivation irrespective of fiber source....

  19. Sensitive determination of THC and main metabolites in human plasma by means of microextraction in packed sorbent and gas chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Rosado, T; Fernandes, L; Barroso, M; Gallardo, E

    2017-02-01

    Cannabis is one of the most available and consumed illicit drug in the world and its identification and quantification in biological specimens can be a challenge given its low concentrations in body fluids. The present work describes a fast and fully validated procedure for the simultaneous detection and quantification of ▵ 9 -tetrahydrocannabinol (▵ 9_ THC) and its two main metabolites 11-hydroxy ▵ 9_ tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-▵ 9 - tetrahydrocannbinol (THC-COOH) in plasma samples using microextraction by packed sorbent (MEPS) and gas chromatography-tandem mass spectrometry (GC-MS/MS). A small plasma volume (0.25mL) pre-diluted (1:20), was extracted with MEPS M1 sorbent as follows: conditioning (4 cycles of 250μL methanol and 4 cycles of 250μL 0.1% formic acid in water); sample load (26 cycles of 250μL); wash (100μL of 3% acetic acid in water followed by 100μL 5% methanol in water); and elution (6 cycles of 100μL of 10% ammonium hydroxide in methanol). The procedure allowed the quantification of all analytes in the range of 0.1-30ng/mL. Recoveries ranged from 53 to 78% (THC), 57 to 66% (11-OH-THC) and 62 to 65% (THC-COOH), allowing the limits of detection and quantification to be set at 0.1ng/mL for all compounds. Intra-day precision and accuracy revealed coefficients of variation (CVs) lower than 10% at the studied concentrations, with a mean relative error within±9%, while inter-day precision and accuracy showed CVs lower than 15% for all analytes at the tested concentrations, with an inaccuracy within±8%. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Plasma and pleural fluid pharmacokinetics of erlotinib and its active metabolite OSI-420 in patients with non-small-cell lung cancer with pleural effusion.

    Science.gov (United States)

    Masago, Katsuhiro; Togashi, Yosuke; Fukudo, Masahide; Terada, Tomohiro; Irisa, Kaoru; Sakamori, Yuichi; Kim, Young Hak; Mio, Tadashi; Inui, Ken-Ichi; Mishima, Michiaki

    2011-09-01

    Erlotinib is orally active and selectively inhibits the tyrosine kinase activity of the epidermal growth factor receptor. The pleural space penetration and exposure of erlotinib is poorly understood. Thus, we investigated the pharmacokinetics (PK) of erlotinib and its active metabolite OSI-420 in non-small-cell lung cancer (NSCLC) of malignant pleural effusion (MPE). We analyzed the PK of erlotinib and OSI-420 on days 1 and 8 after beginning erlotinib therapy in 9 patients with MPE. Their concentrations were determined by high-performance liquid chromatography with ultraviolet detection. Blood samples were obtained five times per day: before administration, and 2, 4, 8, and 24 hours after administration. Pleural effusions were obtained once per day, 2 hours after administration on day 1, and before administration on day 8. The exceptions were cases 2 and 4, which had pleural effusions obtained just before drug administration, and 2, 4, 8, and 24 hours after administration. The mean percentage of penetration from plasma to pleural effusion for erlotinib was 18% on day 1 and 112% on day 8, while these values for OSI-420 were 9.5% on day 1 and 131% on day 8. The area under the drug concentration-time curve of pleural fluid for erlotinib was 28,406 ng-hr/mL for case 2 and 45,906 ng-hr/mL for case 4. There seems to be a significant accumulation of both erlotinib and OSI-420 in MPE with repeated dosing. Although larger studies will be necessary to determine the true impact of erlotinib MPE accumulation on plasma PK and safety, erlotinib can be administered safely to patients with MPE with respect to efficacy and side effects. Copyright © 2011. Published by Elsevier Inc.

  1. Quantitation of donepezil and its active metabolite 6-O-desmethyl donepezil in human plasma by a selective and sensitive liquid chromatography-tandem mass spectrometric method

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Bhavin N. [Chemistry Department, School of Sciences, Gujarat University, Navrangpura, Ahmedabad 380 009, Gujarat (India); Analytical Laboratory, BA Research India Ltd., Bodakdev, Ahmedabad 380 054, Gujarat (India); Sharma, Naveen [Analytical Laboratory, BA Research India Ltd., Bodakdev, Ahmedabad 380 054, Gujarat (India); Sanyal, Mallika [Chemistry Department, St. Xaviers' College, Navrangpura, Ahmedabad 380 009, Gujarat (India); Shrivastav, Pranav S. [Chemistry Department, School of Sciences, Gujarat University, Navrangpura, Ahmedabad 380 009, Gujarat (India)], E-mail: pranav_shrivastav@yahoo.com

    2008-11-23

    A sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the simultaneous determination of donepezil (D) and its pharmacologically active metabolite, 6-O-desmethyl donepezil (6-ODD) in human plasma is developed using galantamine as internal standard (IS). The analytes and IS were extracted from 500 {mu}L aliquots of human plasma via solid-phase extraction (SPE) on Waters Oasis HLB cartridges. Chromatographic separation was achieved in a run time of 6.0 min on a Waters Novapak C18 (150 mm x 3.9 mm, 4 {mu}m) column under isocratic conditions. Detection of analytes and IS was done by tandem mass spectrometry, operating in positive ion and multiple reaction monitoring (MRM) acquisition mode. The protonated precursor to product ion transitions monitored for D, 6-ODD and IS were at m/z 380.1 {yields} 91.2, 366.3 {yields} 91.3 and 288.2 {yields} 213.2, respectively. The method was fully validated for its selectivity, interference check, sensitivity, linearity, precision and accuracy, recovery, matrix effect, ion suppression/enhancement, cross-specificity, stability and dilution integrity. A linear dynamic range of 0.10-50.0 ng mL{sup -1} for D and 0.02-10.0 ng mL{sup -1} for 6-ODD was evaluated with mean correlation coefficient (r) of 0.9975 and 0.9985, respectively. The intra-batch and inter-batch precision (%CV, coefficient of variation) across five quality control levels was less than 7.5% for both the analytes. The method was successfully applied to a bioequivalence study of 10 mg donepezil tablet formulation in 24 healthy Indian male subjects under fasting condition.

  2. Analysis of fenretinide and its metabolites in human plasma by liquid chromatography-tandem mass spectrometry and its application to clinical pharmacokinetics.

    Science.gov (United States)

    Cho, Hwang Eui; Min, H Kang

    2017-01-05

    A simple and accurate high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the determination of N-(4-hydroxyphenyl)retinamide (fenretinide, 4-HPR) and its metabolites, 4-oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR) and N-(4-methoxyphenyl)retinamide (4-MPR), in human plasma. Plasma samples were prepared using protein precipitation with ethanol. Chromatographic separation of the three analytes and N-(4-ethoxyphenyl)retinamide (4-EPR), an internal standard, was achieved on a Zorbax SB-C18 column (3.5μm, 50×2.1mm) using gradient elution with the mobile phase of 0.1% formic acid in water and acetonitrile (pH* 2.4) at a flow rate of 0.5mL/min. Electrospray ionization (ESI) mass spectrometry was operated in the positive ion mode with multiple reaction monitoring (MRM). The calibration curves obtained were linear over the concentration range of 0.2-50ng/mL with a lower limit of quantification of 0.2ng/mL. The relative standard deviation of intra-day and inter-day precision was below 7.64%, and the accuracy ranged from 94.92 to 105.43%. The extraction recoveries were found to be higher than 90.39% and no matrix effect was observed. The analytes were stable for the durations of the stability studies. The validated method was successfully applied to the analyses of the pharmacokinetic study for patients treated with 4-HPR in a clinical trial. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Development of an HPLC fluorescence method for determination of boldine in plasma, bile and urine of rats and identification of its major metabolites by LC-MS/MS.

    Science.gov (United States)

    Hroch, Miloš; Mičuda, Stanislav; Cermanová, Jolana; Chládek, Jaroslav; Tomšík, Pavel

    2013-10-01

    Boldine belongs to the group of aporphine alkaloids isolated from Boldo tree. In contrast with numerous reports on the pharmacological effects of boldine, the data about its pharmacokinetics and biotransformation are scarce. No validated bioanalytical method of sufficient sensitivity has so far been described in the literature which could be used for quantification of boldine in various body fluids collected in pharmacokinetic studies. This work presents, for the first time, the assay for boldine in the plasma, bile and urine of rats. It includes liquid-liquid extraction/back-extraction of boldine, its chromatographic separation and sensitive fluorescence detection. Separation was carried out on a pentafluorophenyl core-shell column (Kinetex PFP, 150×3mm, 2.6μm) in gradient elution mode with solvent system consisting of an acetonitrile-ammonium formate buffer (5mM, pH=3.8). Fluorimetric detection (λEX=320nm, λEM=370nm) was used for quantitative work. Validation according to the EMEA guideline proved the assay LLOQ (0.1μmolL(-1)), linearity over a broad range of 0.1-50μmolL(-1), precision (intra- and inter-day CVs less than 4.5% and 6.1%, respectively) and accuracy (relative errors between -5.8% and 4.8%). In a pilot pharmacokinetic experiment, the concentration-time profiles were described for boldine (single i.v. bolus 50mgkg(-1)) in plasma and bile and cumulative excretion in urine was investigated. The major metabolites identified by means of LC-MS(n) were boldine-O-glucuronide, boldine-O-sulphate and disulphate, boldine-O-glucuronide-O-sulphate and N-demethyl-boldine-O-sulphate. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Development and application of radioimmunological methods to determine an anabolic compound (trenboloneacetate sup(R)) and its major metabolite (trenbolone) in various tissues and in bovine plasma

    International Nuclear Information System (INIS)

    Oettel, G.M.

    1976-01-01

    For quantitation of the anabolic compound trenboloneacetate sup(R)(TBA) and its major metabolite trenbolone (TBOH) a radioimmunoassay (RIA) was established after raising antibodies in rabbits immunized with TBA-3-(o-carboxi-methyl)-oxime-BSA and TBOH-17β-hemisuccinate-BSA. In order to apply this assay for residue determinations in muscle, liver kidney and fat as well as in plasma of treated animals specific extraction procedures were developed. Specifity, sensitivity, accuracy and reproductibility were tested and the developed methods were shown to be highly reliable. Besides free also conjugated TBOH could be determined after enzyme hydrolysis. The lower limit of sensitivity was around 45 pg; at present 100 tissue samples can be analyzed by one person during one week. With the methods described tissue and plasma samples of 41 heifer calves, 10 bull calves and two steers were analyzed for residues of TBA and TBOH. The animals were treated with various dosages of TBA, alone or in combination with oestradiol-17β. In treated animals the highest residue levels were found in liver, with conjugated TBOH being the major residue fraction (76,4%). Second ranking after liver were fat and kidney tissue with similarly high total residue concentrations, however, free TBOH being the major residue fraction (84,1%) in fat, while each, free and conjugated TBOH, accounted for about 50% in kidney. Lowest residue concentrations with free TBOH being the major residue fraction (91,5%) were found in general in muscular tissue. TBA could only be quantitated in fat (14.2% of total residues). (orig.) [de

  5. Multilaboratory Validation of First Action Method 2016.04 for Determination of Four Arsenic Species in Fruit Juice by High-Performance Liquid Chromatography-Inductively Coupled Plasma-Mass Spectrometry.

    Science.gov (United States)

    Kubachka, Kevin; Heitkemper, Douglas T; Conklin, Sean

    2017-07-01

    Before being designated AOAC First Action Official MethodSM 2016.04, the U.S. Food and Drug Administration's method, EAM 4.10 High Performance Liquid Chromatography-Inductively Coupled Plasma-Mass Spectrometric Determination of Four Arsenic Species in Fruit Juice, underwent both a single-laboratory validation and a multilaboratory validation (MLV) study. Three federal and five state regulatory laboratories participated in the MLV study, which is the primary focus of this manuscript. The method was validated for inorganic arsenic (iAs) measured as the sum of the two iAs species arsenite [As(III)] and arsenate [As(V)], dimethylarsinic acid (DMA), and monomethylarsonic acid (MMA) by analyses of 13 juice samples, including three apple juice, three apple juice concentrate, four grape juice, and three pear juice samples. In addition, two water Standard Reference Materials (SRMs) were analyzed. The method LODs and LOQs obtained among the eight laboratories were approximately 0.3 and 2 ng/g, respectively, for each of the analytes and were adequate for the intended purpose of the method. Each laboratory analyzed method blanks, fortified method blanks, reference materials, triplicate portions of each juice sample, and duplicate fortified juice samples (one for each matrix type) at three fortification levels. In general, repeatability and reproducibility of the method was ≤15% RSD for each species present at a concentration >LOQ. The average recovery of fortified analytes for all laboratories ranged from 98 to 104% iAs, DMA, and MMA for all four juice sample matrixes. The average iAs results for SRMs 1640a and 1643e agreed within the range of 96-98% of certified values for total arsenic.

  6. Simultaneous quantitation of atorvastatin and its two active metabolites in human plasma by liquid chromatography/(– electrospray tandem mass spectrometry

    Directory of Open Access Journals (Sweden)

    Pankaj Partani

    2014-02-01

    Full Text Available A sensitive, accurate and selective liquid chromatography–tandem mass spectrometry method (LC–MS/MS was developed and validated for the simultaneous quantitation of atorvastatin (AT and its equipotent hydroxyl metabolites, 2-hydroxy atorvastatin (2-AT and 4-hydroxy atorvastatin (4-AT, in human plasma. Electrospray ionization (ESI interface in negative ion mode was selected to improve the selectivity and the sensitivity required for this application. Additionally, a solid phase extraction (SPE step was performed to reduce any ion-suppression and/or enhancement effects. The separation of all compounds was achieved in less than 6 min using a C18 reverse-phase fused-core® column and a mobile phase, composed of a mixture of 0.005% formic acid in water:acetonitrile:methanol (35:25:40, v/v/v, in isocratic mode at a flow rate of 0.6 mL/min. The method has lower limit of quantitation (LLOQ of 0.050 ng/mL for all analytes. The method has shown tremendous reproducibility, with intra- and inter-day precision less than 6.6%, and intra- and inter-day accuracy within ±4.3% of nominal values, for all analytes, and has proved to be highly reliable for the analysis of clinical samples. Keywords: Atorvastatin, LC–MS/MS, Solid phase extraction, Pharmacokinetics, Method validation

  7. Liquid Chromatography/Tandem Mass Spectrometry for the Simultaneous Determination of Ursodiol and its Major Metabolites, Tauroursodeoxycholic Acid and Glycoursodeoxycholic Acid in Human Plasma

    Directory of Open Access Journals (Sweden)

    M. Ganesan

    2012-01-01

    Full Text Available A rapid and sensitive method is described for the quantification of ursodiol and its major metabolites glycoursodeoxycholic acid (GUDCA and tauroursodeoxycholic acid (TUDCA in human plasma using single internal standard (Ursodeoxycholic Acid d4. Solid phase extraction was performed and chromatographic separation of 5µL injected sample was achieved using Waters Xterra, 5µm column with a mobile phase comprised of methanol and 5 mM ammonium formate with 0.1 % acetic acid ( 70 : 30, v/v . The mass spectrometer was used in negative ion mode and multiple reactions monitoring using electro spray ionization mode as an interface. The method was fully validated and the calibration curves were linear over the concentration range of 25.9 to 15300.1 ng/mL for ursodiol, 2.7 to 1587.5ng/mLfor tauroursodeoxycholicacid and 25.4 to 15040.9 ng/mL for glycoursodeoxycholic acid. The method was sensitive and specific, with the lower limit of quantification of 25.9, 2.7 and 25.4 ng/ml for ursodiol, tauroursodeoxycholic acid and glycoursodeoxycholic acid respectively. The present method includes a simple and rapid sample preparation with shorter analysis run time and less flow rate compared to previously reported methods. The method was applied successfully for a bioequivalence study in healthy subjects.

  8. Development and validation of an enantioselective SFC-MS/MS method for simultaneous separation and quantification of oxcarbazepine and its chiral metabolites in beagle dog plasma.

    Science.gov (United States)

    Yang, Zhichao; Xu, Xueyu; Sun, Lingxia; Zhao, Xue; Wang, Hao; Fawcett, John Paul; Yang, Yan; Gu, Jingkai

    2016-05-01

    A rapid and sensitive assay based on supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) has been developed and validated for the determination of oxcarbazepine (OXC) and its chiral metabolite licarbazine (Lic) in beagle dog plasma using carbamazepine as internal standard. Chiral analysis in a run time of only 3 min was performed on an ACQUITY UPC(2) ™ Trefoil™ CEL2 column (3.0 × 150 mm, 2.5 μm) at 50 °C by isocratic elution with a mobile phase of supercritical carbon dioxide (purity ≥ 99.99%) and methanol (60:40, v/v) at a flow rate of 2.3 mL/min. The assay was linear over the concentration ranges 5-1000 ng/mL for OXC and 0.5-100 ng/mL for the enantiomers of Lic with corresponding lower limits of quantitation of 5 ng/mL and 0.5 ng/mL. Intra- and inter-day precisions were in the range 0.78-14.14% with accuracies in the range -10.80% to 0.42%. The method was successfully applied to a pharmacokinetic study involving a single oral administration of 16 mg/kg OXC as Trileptal(@) tablets to beagle dogs. Copyright © 2016. Published by Elsevier B.V.

  9. Development and validation of an UHPLC-HRMS protocol for the analysis of flavan-3-ol metabolites and catabolites in urine, plasma and feces of rats fed a red wine proanthocyanidin extract.

    Science.gov (United States)

    Pereira-Caro, Gema; Ordóñez, José Luis; Ludwig, Iziar; Gaillet, Sylvie; Mena, Pedro; Del Rio, Daniele; Rouanet, Jean-Max; Bindon, Keren A; Moreno-Rojas, José Manuel; Crozier, Alan

    2018-06-30

    This study developed, optimized and validated an ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) method to identify and quantify metabolites and microbial-derived catabolites in urine, plasma and feces of rats following ingestion of 50 mg of a red wine proanthocyanidin-rich extract. The method was validated for specificity, linearity, limit of detection (LD) and quantification (LQ), intra-day and inter-day precision, recovery and matrix effects, which were determined for 34 compounds in the three biological matrices. After method validation, three parent flavan-3-ols, four 5-carbon side chain ring fission metabolites, and 27 phenolic acid and aromatic catabolites were quantified in plasma, urine and feces after red wine proanthocyanidin intake. These results establish the value of the UHPLC-HRMS protocol in obtaining a detailed picture of proanthocyanidin metabolites and their microbial-derived catabolites, along with their phase II metabolites, in biological fluids of rat, and potentially in human clinical studies designed to evaluate the bioavailability of dietary flavan-3-ols. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Acylcarnitine Profiles in Plasma and Tissues of Hyperglycemic NZO Mice Correlate with Metabolite Changes of Human Diabetes

    Directory of Open Access Journals (Sweden)

    Anna Weiser

    2018-01-01

    Full Text Available The New Zealand obese (NZO mouse is a polygenic model for obesity and diabetes with obese females and obese, diabetes-prone males, used to study traits of the metabolic syndrome like type 2 diabetes mellitus (T2DM, obesity, and dyslipidaemia. By using LC-MS/MS, we here examine the suitability of this model to mirror tissue-specific changes in acylcarnitine (AC and amino acid (AA species preceding T2DM which may reflect patterns investigated in human metabolism. We observed high concentrations of fatty acid-derived ACs in 11 female mice, high abundance of branched-chain amino acid- (BCAA- derived ACs in 6 male mice, and slight increases in BCAA-derived ACs in the remaining 6 males. Principal component analysis (PCA including all ACs and AAs confirmed our hypothesis especially in plasma samples by clustering females, males with high BCAA-derived ACs, and males with slight increases in BCAA-derived ACs. Concentrations of insulin, blood glucose, NEFAs, and triacylglycerols (TAGs further supported the hypothesis of high BCAA-derived ACs being able to mirror the onset of diabetic traits in male individuals. In conclusion, alterations in AC and AA profiles overlap with observations from human studies indicating the suitability of NZO mice to study metabolic changes preceding human T2DM.

  11. Arsenic: natural and anthropogenic

    National Research Council Canada - National Science Library

    Matschullat, Jörg; Deschamps, Eleonora

    2011-01-01

    .... Based on state-of-the-art investigations into the global arsenic cycle, the related human toxicology and available remediation technologies, it assesses arsenic in all the environmental compartments...

  12. ARSENIC RESEARCH AT GWERD

    Science.gov (United States)

    Abstract - The presentation will summarize the arsenic research program at the Ground Water & Ecosystems Restoration Division of the National Risk Management Research Laboratory of USEPA. Topics include use of permeable reactive barriers for in situ arsenic remediation in ground...

  13. Determination of trace amounts of lead, arsenic, nickel and cobalt in high-purity iron oxide pigment by inductively coupled plasma atomic emission spectrometry after iron matrix removal with extractant-contained resin

    International Nuclear Information System (INIS)

    Xu Yuyu; Zhou Jianfeng; Wang Guoxin; Zhou Jinfan; Tao Guanhong

    2007-01-01

    Inductively coupled plasma atomic emission spectrometry (ICP-AES) was applied to the determination of lead, arsenic, nickel and cobalt in high-purity iron oxide pigment. Samples were dissolved with hydrochloric acid and hydrogen peroxide. The digest was passed through a column, which was packed with a polymer resin containing a neutral organophosphorus extractant, tri-n-butylphosphate. Iron was sorbed selectively on the resin and the analytes of interest passed through the column, allowing the effective separation of them from the iron matrix. Conditions of separation were optimized. The detection limits (3σ) in solution were 10, 40, 7 and 5 μg L -1 , and in pigment were 0.2, 0.8, 0.14 and 0.1 mg kg -1 for lead, arsenic, cobalt and nickel, respectively. The recoveries ranged from 95% to 107% when sample digests were spiked with 5 μg of the analytes of interest, and relative standard deviations (n = 6) were 1.5-17.6% for the determination of the spiked samples. The method was successfully applied to the determination of trace amounts of these elements in high-purity iron oxide pigment samples

  14. A Magnetized Nanoparticle Based Solid-Phase Extraction Procedure Followed by Inductively Coupled Plasma Atomic Emission Spectrometry to Determine Arsenic, Lead and Cadmium in Water, Milk, Indian Rice and Red Tea.

    Science.gov (United States)

    Azimi, Salameh; Es'haghi, Zarrin

    2017-06-01

    A sensitive and simple method using magnetic multi-walled carbon nanotube (MWCNTs-Fe 3 O 4 MNP), as the adsorbent, has been successfully developed for extraction and pre-concentration of arsenic, lead and cadmium with detection by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The nanosorbent was characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction pattern (XRD), vibrating sample magnetometer (VSM) and transmission electron microscopy (TEM). The key factors affecting the signal intensity such as pH, adsorbent amount, etc. were investigated. Under optimal conditions, the limits of detection (three-time of signal to noise ratio, S/N 3) were 0.3, 0.6, 0.3 ng/mL for arsenic, lead and cadmium, respectively. Application of the adsorbent was investigated by the analysis of water, milk, Indian rice and red tea. The experimental data was analyzed and obeyed Langmuir and Freundlich adsorption models. The kinetic data was fitted to the pseudo-second-order model. Thermodynamic studies revealed the feasibility and exothermic nature of the system.

  15. Potential application of SERS for arsenic speciation in biological matrices.

    Science.gov (United States)

    Yang, Mingwei; Matulis, Shannon; Boise, Lawrence H; McGoron, Anthony J; Cai, Yong

    2017-08-01

    Speciation of arsenic is usually carried out using chromatography-based methods coupled with spectroscopic determination; however, the inevitable procedures involving sample preparation and separation could potentially alter the integrity of the arsenic metabolites present in biological samples. Surface-enhanced Raman spectroscopy (SERS) could be a promising alternative for providing a reliable arsenic analysis under the influence of a cellular matrix. A method for arsenic speciation using SERS in cellular matrix was developed in this study and four arsenicals were selected, including arsenite (As III ), arsenate (As V ), monomethylarsonic acid (MMA V ) and dimethylarsinic acid (DMA V ). Silver nanoparticles in the form of colliodal suspension with different surface charges, i.e., coated with citrate (AgNPs-Citrate) and spermine (AgNPs-Spermine) were employed as SERS substrates. Adsorption of arsenicals on nanoparticles in colloidal suspensions and the cellular matrix and the pH, size, and zeta potential of the colloidal suspensions were investigated for a better understanding of the SERS signal response of arsenicals in the colloidal suspensions or under the influence of cellular matrix. Arsenicals showed substantially different SERS responses in the two colloidal suspensions, mainly because of the distinct difference in the interaction between the arsenicals and the nanoparticles. Arsenic speciation in cell lysate could be successfully carried out in AgNPs-Spermine suspension, while AgNPs-Citrate could not yield significant SERS signals under the experimental conditions. This study proved that AgNPs-Spermine colloidal suspension could be a promising SERS substrate for studying arsenic metabolism in a biological matrix, reducing the bias caused by traditional techniques that involve sample extraction and pretreatment.

  16. Arsenic pollution sources.

    Science.gov (United States)

    Garelick, Hemda; Jones, Huw; Dybowska, Agnieszka; Valsami-Jones, Eugenia

    2008-01-01

    Arsenic is a widely dispersed element in the Earth's crust and exists at an average concentration of approximately 5 mg/kg. There are many possible routes of human exposure to arsenic from both natural and anthropogenic sources. Arsenic occurs as a constituent in more than 200 minerals, although it primarily exists as arsenopyrite and as a constituent in several other sulfide minerals. The introduction of arsenic into drinking water can occur as a result of its natural geological presence in local bedrock. Arsenic-containing bedrock formations of this sort are known in Bangladesh, West Bengal (India), and regions of China, and many cases of endemic contamination by arsenic with serious consequences to human health are known from these areas. Significant natural contamination of surface waters and soil can arise when arsenic-rich geothermal fluids come into contact with surface waters. When humans are implicated in causing or exacerbating arsenic pollution, the cause can almost always be traced to mining or mining-related activities. Arsenic exists in many oxidation states, with arsenic (III) and (V) being the most common forms. Similar to many metalloids, the prevalence of particular species of arsenic depends greatly on the pH and redox conditions of the matrix in which it exists. Speciation is also important in determining the toxicity of arsenic. Arsenic minerals exist in the environment principally as sulfides, oxides, and phosphates. In igneous rocks, only those of volcanic origin are implicated in high aqueous arsenic concentrations. Sedimentary rocks tend not to bear high arsenic loads, and common matrices such as sands and sandstones contain lower concentrations owing to the dominance of quartz and feldspars. Groundwater contamination by arsenic arises from sources of arsenopyrite, base metal sulfides, realgar and orpiment, arsenic-rich pyrite, and iron oxyhydroxide. Mechanisms by which arsenic is released from minerals are varied and are accounted for by

  17. Quantification of vorinostat and its main metabolites in plasma and intracellular vorinostat in PBMCs by liquid chromatography coupled to tandem mass spectrometry and its relation to histone deacetylase activity in human blood.

    Science.gov (United States)

    Liu, Lu; Detering, Jan-Christoph; Milde, Till; Haefeli, Walter Emil; Witt, Olaf; Burhenne, Jürgen

    2014-08-01

    Vorinostat (suberoylanilide hydroxamic acid) is the first approved histone deacetylase (HDAC) inhibitor for the treatment of cutaneous T-cell lymphoma after progressive disease following two systemic therapies. Intracellular access of vorinostat is essential to exert its epigenetic effects. Therefore, we studied the relationship between vorinostat extracellular (plasma) and intracellular (peripheral blood mononuclear cells, PBMCs) concentration and assessed its concentration-effect relationship by HDAC activity testing. Assays were developed and validated for the low nanomolar quantification of vorinostat and two inactive metabolites in human plasma and PBMCs. For the vorinostat extraction from plasma and PBMCs solid-phase extraction and liquid-liquid extraction methods were applied. Extraction recoveries ranged from 88.6% to 114.4% for all analytes and extraction methods. Extracts were chromatographed on a Phenomenex Luna column isocratically (plasma) or by gradient (PBMCs) consisting of acidic ammonium acetate, acetonitrile, and methanol. The analytes were quantified using deuterated internal standards and positive electrospray tandem mass spectrometry (multiple reaction monitoring) with lower limits of quantification of 11.0 ng/mL (plasma) and 0.1 ng/3 × 10(6) cells (PBMCs). The calibrated ranges were linear for vorinostat in plasma 11.0-1100 (11,000) ng/mL (metabolites) and PBMCs 0.1-10.0 ng/3 × 10(6) cells with correlation coefficients >0.99, an overall accuracy varying between -6.7% and +3.8% in plasma, -8.1% and -1.5% in PBMCs, and an overall precision ranging from 3.2% to 6.1% in plasma and 0.8% to 4.0% in PBMCs (SD batch-to-batch). The application to blood samples from healthy volunteers incubated with vorinostat revealed accumulation of vorinostat in PBMCs, effective intracellular HDAC inhibition at therapeutic vorinostat concentrations and a direct vorinostat concentration dependency to HDAC inhibition. Copyright © 2014 Elsevier B.V. All rights

  18. Arsenic biotransformation and volatilization in transgenic rice

    Science.gov (United States)

    Meng, Xiang-Yan; Qin, Jie; Wang, Li-Hong; Duan, Gui-Lan; Sun, Guo-Xin; Wu, Hui-Lan; Chu, Cheng-Cai; Ling, Hong-Qing; Rosen, Barry P.; Zhu, Yong-Guan

    2011-01-01

    Summary Biotransformation of arsenic includes oxidation, reduction, methylation and conversion to more complex organic arsenicals. Members of the class of arsenite [As(III)] S-adenosylmethyltransferase enzymes catalyze As(III) methylation to a variety of mono-, di- and trimethylated species, some of which are less toxic than As(III) itself. However, no methyltransferase gene has been identified in plants. Here, an arsM gene from the soil bacterium Rhodopseudomonas palustris was expressed in Japonica rice (Oryza sativa L.) cultivar Nipponbare, and the transgenic rice produced methylated arsenic species, which were measured by inductively coupled plasma mass spectrometry (ICP-MS) and high performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS). Both monomethylarsenate [MAs(V)] and dimethylarsenate [DMAs(V)] were detected in the root and shoot of transgenic rice. After 12-d exposure to As(III), the transgenic rice gave off 10-fold more volatile arsenicals. The present study demonstrates that expression of an arsM gene in rice induces arsenic methylation and volatilization, providing a potential stratagem for phytoremediation theoretically. PMID:21517874

  19. Determination of the phytochemical composition of Jingning fang and the in vivo pharmacokinetics of its metabolites in rat plasma by UPLC-MS/MS.

    Science.gov (United States)

    Yang, Chunjing; Yin, XingBin; Dong, Xiaoxv; Zhang, Xin; You, Longtai; Wang, Wenping; Wang, Junhong; Chen, Qinghe; Ni, Jian

    2017-11-01

    Jingning fang (JNF) is an effective Traditional Chinese Medicine (TCM) which is used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). To clarify the bioactive constituents of JNF, a Thermo Q Exactive™ Plus Orbitrap™ mass spectrometer was used in this study. More than 127 chemical compounds were isolated and identified tentatively in the JNF extract, while 42 prototype constituents with 4 potential metabolites were identified tentatively in rat plasma. A method for simultaneous determination of polygalaxanthone III (PAIII), sibiricose A 5 (A 5 ), sibiricose A 6 (A 6 ), 3, 6'-disinapoyl sucrose (3,6'-DISS), tenuifoliside C (TEC), tenuifolin B (TNB), verbascoside (VCE), heterophyllin B (HEB) and schisandrin (SCH) in rat was developed and validated using polydatin (PLN) and psoralen (PSN) as internal standards. All calibration curves proved favorable linearity (R 2 ≥0.9923) in linear ranges. The lower limit of quantification (LLOQ) was 2.5ng/mL for PAIII, A 5 , 3, 6'-DISS, TNB, VCE, HEB and SCH, 1.0ng/mL for A 6 and TEC, respectively. Intra-day and inter-day precisions didn't exceed 14.0% for all the analytes. Extraction recoveries and matrix effects of analytes and IS were acceptable. The validated method has been successfully applied to the pharmacokinetics (PK) studies of the nine compounds in JNF. These findings are useful for predicting the bioactive components of JNF, and will aid in optimizing dose regimens of the drug. Copyright © 2017. Published by Elsevier B.V.

  20. Simultaneous determination of clevidipine and its primary metabolite in dog plasma by liquid chromatography-tandem mass spectrometry: Application to pharmacokinetic study.

    Science.gov (United States)

    Zhou, Ying; Li, Huqun; He, Xiaomeng; Jia, Mengmeng; Ni, Yang; Xu, Mingzhen; Chen, Hui; Li, Weiyong

    2014-11-01

    A simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of clevidipine and its primary metabolite H152/81 in dog plasma after protein precipitation with acetonitrile using felodipine as the internal standard (IS). Chromatographic separation was performed on a XB C18 column (2.1mm×50mm, 3.5μm) under isocratic conditions with the mobile phase consisting of acetonitrile and 20mM ammonium acetate buffer (pH 7.0) (40:60, v/v) at the flow rate of 0.3ml/min. The run time was 5.5min. Mass spectrometric analysis was performed on a triple quadrupole mass spectrometer operated in the multiple reaction monitoring (MRM) mode with the transitions of m/z 473.0→338.2 for clevidipine, m/z 356.1→324.0 for H152/81 and m/z 383.9→338.2 for the IS. The method was fully validated in terms of selectivity, linearity, lower limit of quantification (LLOQ), accuracy, precision, stability, matrix effect and recovery over a concentration range of 0.15-200ng/ml for clevidipine and 10-2000ng/ml for H152/81, respectively. The analytical method was applied to support a pharmacokinetic study of simultaneous determination of clevidipine and H152/81 in ten healthy beagle dogs. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Application of ICP-MS and HPLC-ICP-MS for diagnosis and therapy of a severe intoxication with hexavalent chromium and inorganic arsenic.

    Science.gov (United States)

    Heitland, Peter; Blohm, Martin; Breuer, Christian; Brinkert, Florian; Achilles, Eike Gert; Pukite, Ieva; Köster, Helmut Dietrich

    2017-05-01

    ICP-MS and HPLC-ICP-MS were applied for diagnosis and therapeutic monitoring in a severe intoxication with a liquid containing hexavalent chromium (Cr(VI)) and inorganic arsenic (iAs). In this rare case a liver transplantation of was considered as the only chance of survival. We developed and applied methods for the determination of Cr(VI) in erythrocytes and total chromium (Cr) and arsenic (As) in blood, plasma, urine and liver tissue by ICP-MS. Exposure to iAs was diagnosed by determination of iAs species and their metabolites in urine by anion exchange HPLC-ICP-MS. Three days after ingestion of the liquid the total Cr concentrations were 2180 and 1070μg/L in whole blood and plasma, respectively, and 4540μg/L Cr(VI) in erythrocytes. The arsenic concentration in blood was 206μg/L. The urinary As species concentrations were <0.5, 109, 115, 154 and 126μg/L for arsenobetaine, As(III), As(V), methylarsonate (V) and dimethylarsinate (V), respectively. Total Cr and As concentrations in the explanted liver were 11.7 and 0.9mg/kg, respectively. Further analytical results of this case study are tabulated and provide valuable data for physicians and toxicologists. Copyright © 2017. Published by Elsevier GmbH.

  2. Biomarker discovery in biological specimens (plasma, hair, liver and kidney) of diabetic mice based upon metabolite profiling using ultra-performance liquid chromatography with electrospray ionization time-of-flight mass spectrometry.

    Science.gov (United States)

    Tsutsui, Haruhito; Maeda, Toshio; Min, Jun Zhe; Inagaki, Shinsuke; Higashi, Tatsuya; Kagawa, Yoshiyuki; Toyo'oka, Toshimasa

    2011-05-12

    The number of diabetic patients has recently been increasing worldwide. Diabetes is a multifactorial disorder based on environmental factors and genetic background. In many cases, diabetes is asymptomatic for a long period and the patient is not aware of the disease. Therefore, the potential biomarker(s), leading to the early detection and/or prevention of diabetes mellitus, are strongly required. However, the diagnosis of the prediabetic state in humans is a very difficult issue, because the lifestyle is variable in each person. Although the development of a diagnosis method in humans is the goal of our research, the extraction and structural identification of biomarker candidates in several biological specimens (i.e., plasma, hair, liver and kidney) of ddY strain mice, which undergo naturally occurring diabetes along with aging, were carried out based upon a metabolite profiling study. The low-molecular-mass compounds including metabolites in the biological specimens of diabetic mice (ddY-H) and normal mice (ddY-L) were globally separated by ultra-performance liquid chromatography (UPLC) using different reversed-phase columns (i.e., T3-C18 and HS-F5) and detected by electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS). The biomarker candidates related to diabetes mellitus were extracted from a multivariate statistical analysis, such as an orthogonal partial least-squares-discriminant analysis (OPLS-DA), followed by a database search, such as ChemSpider, KEGG and HMDB. Many metabolites and unknown compounds in each biological specimen were detected as the biomarker candidates related to diabetic mellitus. Among them, the elucidation of the chemical structures of several possible metabolites, including more than two biological specimens, was carried out along with the comparison of the tandem MS/MS analyses using authentic compounds. One metabolite was clearly identified as N-acetyl-L-leucine based upon the MS/MS spectra and the retention time on

  3. New Modified UPLC/Tandem Mass Spectrometry Method for Determination of Risperidone and Its Active Metabolite 9-Hydroxyrisperidone in Plasma: Application to Dose-Dependent Pharmacokinetic Study in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Essam Ezzeldin

    2017-01-01

    Full Text Available Sensitive and specific liquid-chromatography tandem mass spectrometry (UPLC-MS/MS assay has been developed and validated for simultaneous quantification of risperidone (RIS and its active metabolite 9-hydroxyrisperidone (9-OH-RIS in rat plasma using olanzapine (OLA as internal standard (IS. Pharmacokinetics of risperidone and its active metabolite 9-hydroxyrisperidone was compared across different doses (0.3, 1.0, and 6.0 mg/kg. Serial blood sample was collected over a time of 48 hours and analyzed for risperidone and its active metabolite 9-hydroxyrisperidone. The pharmacokinetics parameters including Cmax, tmax, and AUC were determined for risperidone and its active ingredient. The method was linear in the concentration range of 0.2–500 ng/mL for risperidone and 9-OH-risperidone, with coefficients of determination greater than 0.998 and lower limit of quantitation of 0.2 ng/mL. Blood levels of risperidone and its active metabolite were roughly dose-proportional. The method developed herein is simple and rapid and was successfully applied for dose-dependent pharmacokinetic study.

  4. Determination of vitamins D2, D3, K1 and K3 and some hydroxy metabolites of vitamin D3 in plasma using a continuous clean-up-preconcentration procedure coupled on-line with liquid chromatography-UV detection.

    Science.gov (United States)

    Ortiz Boyer, F; Fernández Romero, J M; Luque de Castro, M D; Quesada, J M

    1999-03-01

    A semi-automatic procedure for the continuous clean-up and concentration of several fat-soluble vitamins prior to their separation by HPLC and UV detection is reported. The procedure is based on the use of a minicolumn packed with aminopropylsilica as sorbent located prior to the chromatographic detection system. The overall process was developed and applied to the main liposoluble vitamins (A, D2, D3, E, K1, K3) and several hydroxy metabolites of vitamin D3 [25-(OH)-D3,24,25-(OH)2-D3 and 1,25-(OH)2-D3]. All the analytes were monitored at a compromise wavelength of 270 nm. Calibration graphs were constructed between 0.01 and 100 ng ml-1 for vitamin D2 and D3 and their hydroxy metabolites, between 0.1 and 100 ng ml-1 for vitamin A, K1 and K3 and between 1 and 100 ng ml-1 for vitamin E, with excellent regression coefficients (> or = 0.9901) in all cases. The precision was established at two concentration levels with acceptable RSDs in all instances (between 3.6 and 8.7%). The method was appropriate for the determination of vitamin D2, D3, K1 and K3 and the 24,25-dihydroxy and 25-hydroxy metabolites of vitamin D3 in human plasma. The method was applied to plasma samples spiked with the target analytes and the recoveries ranged between 78 and 109%.

  5. AS3MT-mediated tolerance to arsenic evolved by multiple independent horizontal gene transfers from bacteria to eukaryotes

    DEFF Research Database (Denmark)

    Palmgren, Michael; Engström, Karin; Hallström, Björn M.

    2017-01-01

    the evolutionary origin of AS3MT and assessed the ability of different genotypes to produce methylated arsenic metabolites. Phylogenetic analysis suggests that multiple, independent horizontal gene transfers between different bacteria, and from bacteria to eukaryotes, increased tolerance to environmental arsenic...

  6. Environmental arsenic exposure, selenium and sputum alpha-1 antitrypsin

    DEFF Research Database (Denmark)

    Burgess, Jefferey L; Kurzius-Spencer, Margaret; Poplin, Gerald S

    2014-01-01

    Exposure to arsenic in drinking water is associated with increased respiratory disease. Alpha-1 antitrypsin (AAT) protects the lung against tissue destruction. The objective of this study was to determine whether arsenic exposure is associated with changes in airway AAT concentration and whether...... this relationship is modified by selenium. A total of 55 subjects were evaluated in Ajo and Tucson, Arizona. Tap water and first morning void urine were analyzed for arsenic species, induced sputum for AAT and toenails for selenium and arsenic. Household tap-water arsenic, toenail arsenic and urinary inorganic...... arsenic and metabolites were significantly higher in Ajo (20.6±3.5 μg/l, 0.54±0.77 μg/g and 27.7±21.2 μg/l, respectively) than in Tucson (3.9±2.5 μg/l, 0.16±0.20 μg/g and 13.0±13.8 μg/l, respectively). In multivariable models, urinary monomethylarsonic acid (MMA) was negatively, and toenail selenium...

  7. The Association of Arsenic Exposure and Arsenic Metabolism with the Metabolic Syndrome and its Individual Components: Prospective Evidence from the Strong Heart Family Study.

    Science.gov (United States)

    Spratlen, Miranda J; Grau-Perez, Maria; Best, Lyle G; Yracheta, Joseph; Lazo, Mariana; Vaidya, Dhananjay; Balakrishnan, Poojitha; Gamble, Mary V; Francesconi, Kevin A; Goessler, Walter; Cole, Shelley A; Umans, Jason G; Howard, Barbara V; Navas-Acien, Ana

    2018-03-15

    Inorganic arsenic exposure is ubiquitous and both exposure and inter-individual differences in its metabolism have been associated with cardiometabolic risk. The association between arsenic exposure and arsenic metabolism with metabolic syndrome and its individual components, however, is relatively unknown. We used poisson regression with robust variance to evaluate the association between baseline arsenic exposure (urine arsenic levels) and metabolism (relative percentage of arsenic species over their sum) with incident metabolic syndrome and its individual components (elevated waist circumference, elevated triglycerides, reduced HDL, hypertension, elevated fasting plasma glucose) in 1,047 participants from the Strong Heart Family Study, a prospective family-based cohort in American Indian communities (baseline visits in 1998-1999 and 2001-2003, follow-up visits in 2001-2003 and 2006-2009). 32% of participants developed metabolic syndrome over follow-up. An IQR increase in arsenic exposure was associated with 1.19 (95% CI: 1.01, 1.41) greater risk for elevated fasting plasma glucose but not with other individual components or overall metabolic syndrome. Arsenic metabolism, specifically lower MMA% and higher DMA% was associated with higher risk of overall metabolic syndrome and elevated waist circumference, but not with any other component. These findings support there is a contrasting and independent association between arsenic exposure and arsenic metabolism with metabolic outcomes which may contribute to overall diabetes risk.

  8. Environmental Source of Arsenic Exposure

    OpenAIRE

    Chung, Jin-Yong; Yu, Seung-Do; Hong, Young-Seoub

    2014-01-01

    Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a ...

  9. Shredded beet pulp substituted for corn silage in diets fed to dairy cows under ambient heat stress: Feed intake, total-tract digestibility, plasma metabolites, and milk production.

    Science.gov (United States)

    Naderi, N; Ghorbani, G R; Sadeghi-Sefidmazgi, A; Nasrollahi, S M; Beauchemin, K A

    2016-11-01

    ammonia-nitrogen and milk concentration of urea, corresponding to an increase in percentage of protein in milk. Compared with multiparous cows, primiparous cows had greater rumen pH, metabolite concentrations in plasma (glucose, cholesterol, urea nitrogen, total protein, and globulins), milk production, and concentrations of milk components. Substituting beet pulp for corn silage at up to 12% of dietary dry matter can be beneficial during heat stress conditions. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  10. Chronic arsenic exposure increases TGFalpha concentration in bladder urothelial cells of Mexican populations environmentally exposed to inorganic arsenic

    International Nuclear Information System (INIS)

    Valenzuela, Olga L.; Germolec, Dori R.; Borja-Aburto, Victor H.; Contreras-Ruiz, Jose; Garcia-Vargas, Gonzalo G.; Razo, Luz M. del

    2007-01-01

    Inorganic arsenic (iAs) is a well-established carcinogen and human exposure has been associated with a variety of cancers including those of skin, lung, and bladder. High expression of transforming growth factor alpha (TGF-α) has associated with local relapses in early stages of urinary bladder cancer. iAs exposures are at least in part determined by the rate of formation and composition of iAs metabolites (MAs III , MAs V , DMAs III , DMAs V ). This study examines the relationship between TGF-α concentration in exfoliated bladder urothelial cells (BUC) separated from urine and urinary arsenic species in 72 resident women (18-51 years old) from areas exposed to different concentrations of iAs in drinking water (2-378 ppb) in central Mexico. Urinary arsenic species, including trivalent methylated metabolites were measured by hydride generation atomic absorption spectrometry method. The concentration of TGF-α in BUC was measured using an ELISA assay. Results show a statistically significant positive correlation between TGF-α concentration in BUC and each of the six arsenic species present in urine. The multivariate linear regression analyses show that the increment of TGF-α levels in BUC was importantly associated with the presence of arsenic species after adjusting by age, and presence of urinary infection. People from areas with high arsenic exposure had a significantly higher TGF-α concentration in BUC than people from areas of low arsenic exposure (128.8 vs. 64.4 pg/mg protein; p < 0.05). Notably, exfoliated cells isolated from individuals with skin lesions contained significantly greater amount of TGF-α than cells from individuals without skin lesions: 157.7 vs. 64.9 pg/mg protein (p = 0.003). These results suggest that TGF-α in exfoliated BUC may serve as a susceptibility marker of adverse health effects on epithelial tissue in arsenic-endemic areas

  11. Arsenic Accumulation in Rice and Probable Mitigation Approaches: A Review

    Directory of Open Access Journals (Sweden)

    Anindita Mitra

    2017-10-01

    Full Text Available According to recent reports, millions of people across the globe are suffering from arsenic (As toxicity. Arsenic is present in different oxidative states in the environment and enters in the food chain through soil and water. In the agricultural field, irrigation with arsenic contaminated water, that is, having a higher level of arsenic contamination on the top soil, which may affects the quality of crop production. The major crop like rice (Oryza sativa L. requires a considerable amount of water to complete its lifecycle. Rice plants potentially accumulate arsenic, particularly inorganic arsenic (iAs from the field, in different body parts including grains. Different transporters have been reported in assisting the accumulation of arsenic in plant cells; for example, arsenate (AsV is absorbed with the help of phosphate transporters, and arsenite (AsIII through nodulin 26-like intrinsic protein (NIP by the silicon transport pathway and plasma membrane intrinsic protein aquaporins. Researchers and practitioners are trying their level best to mitigate the problem of As contamination in rice. However, the solution strategies vary considerably with various factors, such as cultural practices, soil, water, and environmental/economic conditions, etc. The contemporary work on rice to explain arsenic uptake, transport, and metabolism processes at rhizosphere, may help to formulate better plans. Common agronomical practices like rain water harvesting for crop irrigation, use of natural components that help in arsenic methylation, and biotechnological approaches may explore how to reduce arsenic uptake by food crops. This review will encompass the research advances and practical agronomic strategies on arsenic contamination in rice crop.

  12. An HPLC tandem mass spectrometry for quantification of ET-26-HCl and its major metabolite in plasma and application to a pharmacokinetic study in rats.

    Science.gov (United States)

    Chen, Xu; Zhang, Wensheng; Rios, Sandy; Morkos, Miriam B; Ye, Xiaoli; Li, Gen; Jiang, Xuehua; Wang, Zhijun; Wang, Ling

    2018-02-05

    ET-26-HCl is a new analog of etomidate, a short-acting anesthetic drug, with less adrenal cortex inhibition. The pharmacokinetics of ET-26-HCl in rats needs to be determined for future clinical trials in human subjects. In order to facilitate the pharmacokinetic study, a liquid chromatography based tandem mass spectrometric (HPLC-MS/MS) method was developed and validated for quantification of ET-26-HCl and its major metabolite, ET-26-acid. These two compounds and gabapentin (internal standard) were extracted using a protein precipitation method with methanol and detected by Multiple Reaction Monitoring of m/z transition of 275.6-170.9, 217.7-113.1, and 172.5-154.3 for ET-26-HCl, ET-26-acid, and gabapentin respectively. This method was validated in terms of sensitivity, linearity, reproducibility, and stability. The HPLC-MS/MS method was found linear over the concentration ranges of 21.76-4352ng/mL, and 18.62-3724ng/mL with LLOQ of 21.76 and 18.62ng/mL for ET-26-HCl and ET-26-acid respectively. The mean intra-day and inter-day accuracy was between 94.11-107.78%, while the precision was within the limit of 15.0% for all the quality control samples. A pharmacokinetic study was then conducted in rats following intravenous injection of 2.1, 4.2, and 8.4mg/kg. The linear pharmacokinetics of ET-26-HCl was observed over the dose range of 2.1-8.4mg/kg. The average terminal phase elimination half-lives were 0.87 and 1.03h for ET-26-HCl and ET-26-acid respectively. In summary, an HPLC-MS/MS method for quantification of ET-26-HCl in rat plasma has been developed and successfully applied to a pharmacokinetic study. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Live animal measurements, carcass composition and plasma hormone and metabolite concentrations in male progeny of sires differing in genetic merit for beef production.

    Science.gov (United States)

    Clarke, A M; Drennan, M J; McGee, M; Kenny, D A; Evans, R D; Berry, D P

    2009-07-01

    In genetic improvement programmes for beef cattle, the effect of selecting for a given trait or index on other economically important traits, or their predictors, must be quantified to ensure no deleterious consequential effects go unnoticed. The objective was to compare live animal measurements, carcass composition and plasma hormone and metabolite concentrations of male progeny of sires selected on an economic index in Ireland. This beef carcass index (BCI) is expressed in euros and based on weaning weight, feed intake, carcass weight and carcass conformation and fat scores. The index is used to aid in the genetic comparison of animals for the expected profitability of their progeny at slaughter. A total of 107 progeny from beef sires of high (n = 11) or low (n = 11) genetic merit for the BCI were compared in either a bull (slaughtered at 16 months of age) or steer (slaughtered at 24 months of age) production system, following purchase after weaning (8 months of age) from commercial beef herds. Data were analysed as a 2 × 2 factorial design (two levels of genetic merit by two production systems). Progeny of high BCI sires had heavier carcasses, greater (P animal value (obtained by multiplying carcass weight by carcass value, which was based on the weight of meat in each cut by its commercial value) than progeny of low BCI sires. Regression of progeny performance on sire genetic merit was also undertaken across the entire data set. In steers, the effect of BCI on carcass meat proportion, calculated carcass value (c/kg) and animal value was positive (P carcass fat proportion (P carcass weight followed the same trends as BCI. Muscularity scores, carcass meat proportion and calculated carcass value increased, whereas scanned fat depth, carcass fat and bone proportions decreased with increasing sire EPD for conformation score. The opposite association was observed for sire EPD for fat score. Results from this study show that selection using the BCI had positive

  14. Morphine metabolites

    DEFF Research Database (Denmark)

    Christrup, Lona Louring

    1997-01-01

    , morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) are the major metabolites of morphine. The metabolism of morphine occurs not only in the liver, but may also take place in the brain and the kidneys. The glucuronides are mainly eliminated via bile and urine. Glucuronides as a rule...... are considered as highly polar metabolites unable to cross the blood-brain barrier. Although morphine glucuronidation has been demonstrated in human brain tissue, the capacity is very low compared to that of the liver, indicating that the M3G and M6G concentrations observed in the cerebrospinal fluid (CSF) after...... systemic administration reflect hepatic metabolism of morphine and that the morphine glucuronides, despite their high polarity, can penetrate into the brain. Like morphine, M6G has been shown to be relatively more selective for mu-receptors than for delta- and kappa-receptors while M3G does not appear...

  15. Arsenic levels in the groundwater of Korea and the urinary excretion among contaminated area.

    Science.gov (United States)

    Park, Jung-Duck; Choi, Seong-Jin; Choi, Byung-Sun; Lee, Choong-Ryeol; Kim, Heon; Kim, Yong-Dae; Park, Kyung-Soo; Lee, Young-Jo; Kang, Seojin; Lim, Kyung-Min; Chung, Jin-Ho

    2016-09-01

    Drinking water is a main source of human exposure to arsenic. Hence, the determination of arsenic in groundwater is essential to assess its impact on public health. Here, we report arsenic levels in the groundwater of 722 sites covering all six major provinces of Korea. Water was sampled in two occasions (summer, 722 sites and winter, 636 sites) and the arsenic levels were measured with highly sensitive inductively coupled plasma-mass spectrometry method (limit of detection, 0.1 μg/l) to encompass the current drinking water standard (arsenic in groundwater ranged from 0.1 to 48.4 μg/l. A 88.0-89.0% of sites were 10 μg/l. Notably, urinary arsenic excretion of people around these regions was markedly higher compared with non-contaminated areas (arsenic-contaminated groundwater may contribute to its systemic exposure.

  16. Identification of known chemicals and their metabolites from Alpinia oxyphylla fruit extract in rat plasma using liquid chromatography/tandem mass spectrometry (LC-MS/MS) with selected reaction monitoring.

    Science.gov (United States)

    Chen, Feng; Li, Hai-Long; Tan, Yin-Feng; Li, Yong-Hui; Lai, Wei-Yong; Guan, Wei-Wei; Zhang, Jun-Qing; Zhao, Yuan-Sheng; Qin, Zhen-Miao

    2014-08-01

    Alpinia oxyphylla (Yizhi) capsularfruits are commonly used in traditional medicine. Pharmacological studies have demonstrated that A. oxyphylla capsularfruits have some beneficial roles. Besides volatile oil, sesquiterpenes, diarylheptanoids and flavonoids are main bioactive constituents occurring in the Yizhi capsularfruits. The representative constituents include tectochrysin, izalpinin, chrysin, apigenin-4',7-dimethylether, kaempferide, yakuchinone A, yakuchinone B, oxyphyllacinol and nootkatone. Their content levels in the fruit and its pharmaceutical preparations have been reported by our group. The nine phytochemicals are also the major components present in the Yizhi alcoholic extracts, which have anti-diarrheal activities. However, the fates of these constituents in the body after oral or intravenous administration remain largely unknown. In the present study, we focus on these phytochemicals albeit other concomitant compounds. The chemicals and their metabolites in rat plasma were identified using liquid chromatography/tandem mass spectrometry with selected reaction monitoring mode after orally administered Yizhi extract to rats. Rat plasma samples were treated by methanol precipitation, acidic or enzymatic hydrolysis. This target analysis study revealed that: (1) low or trace plasma levels of parent chemicals were measured after p.o. administration of Yizhi extract, Suoquan capsules and pills to rats; (2) flavonoids and diarylheptanoids formed mainly monoglucuronide metabolites; however, diglucuronide metabolites for chrysin, izalpinin and kaempferide were also detected; (3) metabolic reduction of Yizhi diarylheptanoids occurred in rats. Yakuchinone B was reduced to yakuchinone A and then to oxyphyllacinol in a stepwise manner and subsequently glucuronidated by UDP-glucuronosyl transferase. Further research is needed to characterize the UDP-glucuronosyl transferase and reductase involved in the biotransformation of Yizhi chemicals. Copyright © 2014

  17. Speciation of arsenic in rice and estimation of daily intake of different arsenic species by Brazilians through rice consumption.

    Science.gov (United States)

    Batista, Bruno L; Souza, Juliana M O; De Souza, Samuel S; Barbosa, Fernando

    2011-07-15

    Rice is an important source of essential elements. However, rice may also contain toxic elements such as arsenic. Therefore, in the present study, the concentration of total arsenic and five main chemical species of arsenic (As(3+), As(5+), DMA, MMA and AsB) were evaluated in 44 different rice samples (white, parboiled white, brown, parboiled brown, parboiled organic and organic white) from different Brazilian regions using high-performance liquid chromatography hyphenated to inductively coupled plasma mass spectrometry (HPLC-ICP-MS). The mean level of total arsenic was 222.8 ng g(-1) and the daily intake of inorganic arsenic (the most toxic form) from rice consumption was estimated as 10% of the Provisional Tolerable Daily Intake (PTDI) with a daily ingestion of 88 g of rice. Inorganic arsenic (As(3+), As(5+)) and dimethylarsinic acid (DMA) are the predominant forms in all samples. The percentages of species were 38.7; 39.7; 3.7 and 17.8% for DMA, As(3+), MMA and As(5+), respectively. Moreover, rice samples harvested in the state of Rio Grande do Sul presented more fractions of inorganic arsenic than rice in Minas Gerais or Goiás, which could lead to different risks of arsenic exposure. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. A parallel chiral-achiral liquid chromatographic method for the determination of the stereoisomers of ketamine and ketamine metabolites in the plasma and urine of patients with complex regional pain syndrome

    OpenAIRE

    Moaddel, Ruin; Venkata, Swarajya Lakshmi Vattem; Tanga, Mary J.; Bupp, James E.; Green, Carol E.; Iyer, Lalitha; Furimsky, Anna; Goldberg, Michael E.; Torjman, Marc C.; Wainer, Irving W.

    2010-01-01

    A parallel chiral/achiral LC-MS/MS assay has been developed and validated to measure the plasma and urine concentrations of the enantiomers of ketamine, (R)- and (S)-Ket, in Complex Regional Pain Syndrome (CRPS) patients receiving a 5-day continuous infusion of a sub-anesthetic dose of (R,S)-Ket. The method was also validated for the determination of the enantiomers of the Ket metabolites norketamine, (R)-and (S)-norKet and dehydronorketamine, (R)- and (S)-DHNK, as well as the diastereomeric ...

  19. Methylation of inorganic arsenic in different mammalian species and population groups.

    Science.gov (United States)

    Vahter, M

    1999-01-01

    Thousands of people in different parts of the world are exposed to arsenic via drinking water or contaminated soil or food. The high general toxic of arsenic has been known for centuries, and research during the last decades has shown that arsenic is a potent human carcinogen. However, most experimental cancer studies have failed to demonstrate carcinogenicity in experimental animals, indicating marked variation in sensitivity towards arsenic toxicity between species. It has also been suggested that there is a variation in susceptibility among human individuals. One reason for such variability in toxic response may be variation in metabolism. Inorganic arsenic is methylated in humans as well as animals and micro-organisms, but there are considerable differences between species and individuals. In many, but not all, mammalian species, inorganic arsenic is methylated to methylarsonic acid (MMA) and dimethylarsinic acid (DMA), which are more rapidly excreted in urine than is the inorganic arsenic, especially the trivalent form (AsIII, arsenite) which is highly reactive with tissue components. Absorbed arsenate (AsV) is reduced to trivalent arsenic (AsIII) before the methyl groups are attached. It has been estimated that as much as 50-70% of absorbed AsV is rapidly reduced to AsIII, a reaction which seems to be common for most species. In most experimental animal species, DMA is the main metabolite excreted in urine. Compared to human subjects, very little MMA is produced. However, the rate of methylation varies considerably between species, and several species, e.g. the marmoset monkey and the chimpanzee have been shown not to methylate inorganic arsenic at all. In addition, the marmoset monkey accumulates arsenic in the liver. The rat, on the other hand, has an efficient methylation of arsenic but the formed DMA is to a large extent accumulated in the red blood cells. As a result, the rat shows a low rate of excretion of arsenic. In both human subjects and rodents

  20. Simultaneous measurement of proguanil and its metabolites in human plasma and urine by reversed-phase high-performance liquid chromatography, and its preliminary application in relation to genetically determined S-mephenytoin 4'-hydroxylation status.

    Science.gov (United States)

    Kusaka, M; Setiabudy, R; Chiba, K; Ishizaki, T

    1996-02-01

    A simple high-performance liquid chromatographic (HPLC) assay method was developed for the measurement of proguanil (PG) and its major metabolites, cycloguanil (CG) and 4-chlorophenyl-biguanide (CPB), in human plasma and urine. The assay allowed the simultaneous determination of all analytes in 1 ml of plasma or 0.1 ml of urine. The detection limits of PG, CG, and CPB, defined as the signal-to-noise ratio of 3, were 1 and 5 ng/ml for plasma and urine samples, respectively. Recoveries of the analytes and the internal standard (pyrimethamine) were > 62% from plasma and > 77% from urine. Intra-assay and interassay coefficients of variation for all analytes in plasma and urine were CG and CPB, which ranged from 10% to 15% at one or two concentrations among 4-5 concentrations studied. The clinical applicability of the method was assessed by the preliminary pharmacokinetic study of PG, CG, and CPB in six healthy volunteers with the individually known phenotypes (extensive and poor metabolizers) of S-mephenytoin 4'-hydroxylation, suggesting that individuals with a poor metabolizer phenotype of S-mephenytoin have a much lower capacity to bioactivate PG to CG compared with the extensive metabolizers.

  1. Understanding arsenic carcinogenicity by the use of animal models

    International Nuclear Information System (INIS)

    Wanibuchi, Hideki; Salim, Elsayed I.; Kinoshita, Anna; Shen Jun; Wei Min; Morimura, Keiichirou; Yoshida, Kaoru; Kuroda, Koichi; Endo, Ginji; Fukushima, Shoji

    2004-01-01

    Although numerous epidemiological studies have indicated that human arsenic exposure is associated with increased incidences of bladder, liver, skin, and lung cancers, limited attempts have been made to understand mechanisms of carcinogenicity using animal models. Dimethylarsinic acid (DMA), an organic arsenic compound, is a major metabolite of ingested inorganic arsenics in mammals. Recent in vitro studies have proven DMA to be a potent clastogenic agent, capable of inducing DNA damage including double strand breaks and cross-link formation. In our attempts to clarify DMA carcinogenicity, we have recently shown carcinogenic effects of DMA and its related metabolites using various experimental protocols in rats and mice: (1) a multi-organ promotion bioassay in rats; (2) a two-stage promotion bioassay by DMA of rat urinary bladder and liver carcinogenesis; (3) a 2-year carcinogenicity test of DMA in rats; (4) studies on the effects of DMA on lung carcinogenesis in rats; (5) promotion of skin carcinogenesis by DMA in keratin (K6)/ornithine decarboxylase (ODC) transgenic mice; (6) carcinogenicity of DMA in p53(+/-) knockout and Mmh/8-OXOG-DNA glycolase (OGG1) mutant mice; (7) promoting effects of DMA and related organic arsenicals in rat liver; (8) promoting effects of DMA and related organic arsenicals in a rat multi-organ carcinogenesis test; and (9) 2-year carcinogenicity tests of monomethylarsonic acid (MMA) and trimethylarsine oxide (TMAO) in rats. The results revealed that the adverse effects of arsenic occurred either by promoting and initiating carcinogenesis. These data, as covered in the present review, suggest that several mechanisms may be involved in arsenic carcinogenesis

  2. Toxic Substances Portal- Arsenic

    Science.gov (United States)

    ... is found at low levels in breast milk. top How can families reduce their risk for exposure to arsenic? If you use arsenic-treated wood in home projects, you should wear dust masks, gloves, and protective clothing to decrease exposure to sawdust. ...

  3. Arsenical poisoning of racehorses

    Energy Technology Data Exchange (ETDEWEB)

    Sutherland, G.N.; Fawell, E.V.; Brown, J.K.

    1964-03-07

    A case of arsenic poisoning in a training stable of Thoroughbred racehorses is described. This was due to the accidental spilling of an arsenical rat poison into the corn bin. Nine horses were affected. The mortality rate was 100 per cent. 1 table.

  4. Impact of Cytochrome P450 2D6 Function on the Chiral Blood Plasma Pharmacokinetics of 3,4-Methylenedioxymethamphetamine (MDMA) and Its Phase I and II Metabolites in Humans.

    Science.gov (United States)

    Steuer, Andrea E; Schmidhauser, Corina; Tingelhoff, Eva H; Schmid, Yasmin; Rickli, Anna; Kraemer, Thomas; Liechti, Matthias E

    2016-01-01

    3,4-methylenedioxymethamphetamine (MDMA; ecstasy) metabolism is known to be stereoselective, with preference for S-stereoisomers. Its major metabolic step involves CYP2D6-catalyzed demethylenation to 3,4-dihydroxymethamphetamine (DHMA), followed by methylation and conjugation. Alterations in CYP2D6 genotype and/or phenotype have been associated with higher toxicity. Therefore, the impact of CYP2D6 function on the plasma pharmacokinetics of MDMA and its phase I and II metabolites was tested by comparing extensive metabolizers (EMs), intermediate metabolizers (IMs), and EMs that were pretreated with bupropion as a metabolic inhibitor in a controlled MDMA administration study. Blood plasma samples were collected from 16 healthy participants (13 EMs and three IMs) up to 24 h after MDMA administration in a double-blind, placebo-controlled, four-period, cross-over design, with subjects receiving 1 week placebo or bupropion pretreatment followed by a single placebo or MDMA (125 mg) dose. Bupropion pretreatment increased the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from 0 to 24 h (AUC24) of R-MDMA (9% and 25%, respectively) and S-MDMA (16% and 38%, respectively). Bupropion reduced the Cmax and AUC24 of the CYP2D6-dependently formed metabolite stereoisomers of DHMA 3-sulfate, DHMA 4-sulfate, and 4-hydroxy-3-methoxymethamphetamine (HMMA sulfate and HMMA glucuronide) by approximately 40%. The changes that were observed in IMs were generally comparable to bupropion-pretreated EMs. Although changes in stereoselectivity based on CYP2D6 activity were observed, these likely have low clinical relevance. Bupropion and hydroxybupropion stereoisomer pharmacokinetics were unaltered by MDMA co-administration. The present data might aid further interpretations of toxicity based on CYP2D6-dependent MDMA metabolism.

  5. Impact of Cytochrome P450 2D6 Function on the Chiral Blood Plasma Pharmacokinetics of 3,4-Methylenedioxymethamphetamine (MDMA and Its Phase I and II Metabolites in Humans.

    Directory of Open Access Journals (Sweden)

    Andrea E Steuer

    Full Text Available 3,4-methylenedioxymethamphetamine (MDMA; ecstasy metabolism is known to be stereoselective, with preference for S-stereoisomers. Its major metabolic step involves CYP2D6-catalyzed demethylenation to 3,4-dihydroxymethamphetamine (DHMA, followed by methylation and conjugation. Alterations in CYP2D6 genotype and/or phenotype have been associated with higher toxicity. Therefore, the impact of CYP2D6 function on the plasma pharmacokinetics of MDMA and its phase I and II metabolites was tested by comparing extensive metabolizers (EMs, intermediate metabolizers (IMs, and EMs that were pretreated with bupropion as a metabolic inhibitor in a controlled MDMA administration study. Blood plasma samples were collected from 16 healthy participants (13 EMs and three IMs up to 24 h after MDMA administration in a double-blind, placebo-controlled, four-period, cross-over design, with subjects receiving 1 week placebo or bupropion pretreatment followed by a single placebo or MDMA (125 mg dose. Bupropion pretreatment increased the maximum plasma concentration (Cmax and area under the plasma concentration-time curve from 0 to 24 h (AUC24 of R-MDMA (9% and 25%, respectively and S-MDMA (16% and 38%, respectively. Bupropion reduced the Cmax and AUC24 of the CYP2D6-dependently formed metabolite stereoisomers of DHMA 3-sulfate, DHMA 4-sulfate, and 4-hydroxy-3-methoxymethamphetamine (HMMA sulfate and HMMA glucuronide by approximately 40%. The changes that were observed in IMs were generally comparable to bupropion-pretreated EMs. Although changes in stereoselectivity based on CYP2D6 activity were observed, these likely have low clinical relevance. Bupropion and hydroxybupropion stereoisomer pharmacokinetics were unaltered by MDMA co-administration. The present data might aid further interpretations of toxicity based on CYP2D6-dependent MDMA metabolism.

  6. Simultaneous determination of 3,3',4',5,7-pentamethylquercetin and its possible metabolite 3,3',4',7-tetramethylquercetin in dog plasma by liquid chromatography-tandem mass spectrometry and its application to preclinical pharmacokinetic study.

    Science.gov (United States)

    Chen, Xiaomei; Li, Dongyan; Hu, Yan; Jin, Manwen; Zhou, Liping; Peng, Kelong; Zheng, Heng

    2011-08-01

    A sensitive, simple and rapid ultra fast liquid chromatography (UFLC)-ESI-MS/MS method was established for the simultaneous determination of 3,3',4',5,7-pentamethylquercetin (PMQ) and its possible metabolite 3,3',4',7-tetramethylquercetin (TMQ) in dog plasma using 4',5,7-trimethylapigenin (TMA) as the internal standard. The plasma sample was pretreated with acetonitrile for protein precipitation and the analytes were separated on an Ultimate XB-CN column (5 μm, 2.1 mm × 150 mm) with the mobile phase consisting of acetonitrile and water (2:1, v/v). Detection was performed on a triple-quadrupole tandem mass spectrometer under a positive multiple reaction-monitoring mode (MRM). The mass transition ion-pair was followed as m/z 373.1-312.1 for PMQ, 359.1-344.0 for TMQ and 313.1-298.1 for TMA. The validated concentration ranged from 1.272 to 3060 ng/mL for PMQ and from 10.35 to 1725 ng/mL for TMQ. The lower limit of quantifications for PMQ and TMQ were 1.272 ng/mL and 10.35 ng/mL, respectively. The developed-method was successfully applied for the pharmacokinetic study of PMQ and its metabolite TMQ in dogs following a single oral dose. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. The Profiling and Identification of the Absorbed Constituents and Metabolites of Guizhi Decoction in Rat Plasma and Urine by Rapid Resolution Liquid Chromatography Combined with Quadrupole-Time-of-Flight Mass Spectrometry

    Science.gov (United States)

    Xiang, Hongjun; Zhang, Lishi; Song, Jiannan; Fan, Bin; Nie, Yinglan; Bai, Dong; Lei, Haimin

    2016-01-01

    Guizhi decoction (GZD), a well-known traditional Chinese medicine (TCM) prescription consisting of Ramulus Cinnamomi, Radix Paeoniae Alba, Radix Glycyrrhizae, Fructus Jujubae and Rhizoma Zingiberis Recens, is usually used for the treatment of common colds, influenza, and other pyretic conditions in the clinic. However, the absorbed ingredients and metabolic compounds of GZD have not been reported. In this paper, a method incorporating rapid resolution liquid chromatography (RRLC) with quadrupole-time-of-flight mass spectrometry (Q-TOF-MS) was used to identify ingredients after oral administration of GZD. Identification of the primary components in GZD, drug-containing serum and urine samples was carried out in order to investigate the assimilation and metabolites of the decoction in vivo. By comparing the total ion chromatograms (TICs) of GZD, a total of 71 constituents were detected or characterized. By comparing TICs of blank and dosed rat plasma, a total of 15 constituents were detected and identified as prototypes according to their retention time (tR) and MS, MS/MS data. Based on this, neutral loss scans of 80 and 176 Da in samples of rat plasma and urine helped us to identify most of the metabolites. Results showed that the predominant metabolic pathways of (epi) catechin and gallic acid were sulfation, methylation, glucuronidation and dehydroxylation; the major metabolic pathways of flavone were hydrolysis, sulfation and glucuronidation. Furthermore, degradation, oxidation and ring fission were found to often occur in the metabolism process of GZD in vivo. PMID:27626411

  8. Simultaneous quantification of major cannabinoids and metabolites in human urine and plasma by HPLC-MS/MS and enzyme-alkaline hydrolysis

    NARCIS (Netherlands)

    Aizpurua-Olaizola, Oier; Zarandona, Iratxe; Ortiz, Laura; Navarro, Patricia; Etxebarria, Nestor; Usobiaga, Aresatz

    A high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) method for simultaneous quantification of Δ9-tetrahydrocannabinol (THC), its two metabolites 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH), and four

  9. Consumption of both low and high (-)-epicatechin apple puree attenuates platelet reactivity and increases plasma concentrations of nitric oxide metabolites: A randomized controlled trial

    NARCIS (Netherlands)

    Gasper, A.; Hollands, W.; Casgrain, A.; Saha, S.; Teucher, B.; Dainty, J.R.; Venema, D.P.; Hollman, P.C.H.

    2014-01-01

    We hypothesised that consumption of flavanol-containing apple puree would modulate platelet activity and increase nitric oxide metabolite status, and that high flavanol apple puree would exert a greater effect than low flavanol apple puree. 25 subjects consumed 230 g of apple puree containing 25 and

  10. A novel LC-MS/MS assay for the simultaneous determination of melatonin and its two major metabolites, 6-hydroxymelatonin and 6-sulfatoxymelatonin in dog plasma: Application to a pharmacokinetic study.

    Science.gov (United States)

    Zhao, Huimin; Wang, Yifei; Yuan, Bo; Liu, Shu; Man, Shuang; Xu, Haiyan; Lu, Xiumei

    2016-01-05

    A convenient and specific liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of melatonin (MEL) and its major metabolites, 6-hydroxymelatonin (6-O-MEL) and 6-sulfatoxymelationin (S-O-MEL) in dog plasma. After plasma samples were deproteinized with acetonitrile, the post-treatment samples were analyzed on a Phenomenex Kinetex C18 column (50×2.1 mm, 1.7 μm) interfaced with a triple quadrupole tandem mass spectrometer. Electrospray ionization mode (ESI) and multiple reaction monitoring were used to assay MEL and its metabolites. Acetonitrile and 5 mM ammonium acetate were used as the mobile phase with a gradient elution at a flow rate of 0.2 mL/min. The analytical run time of 6.5 min was divided into two periods according to ionization mode. S-O-MEL was monitored in negative ionization mode (period 1), while MEL and 6-O-MEL were detected in positive ionization mode (period 2). All calibration curves showed good linearity (r>0.991) over the concentration range with a lower limit of quantification (LLOQ) of 0.02 ng/mL for MEL, 0.04 ng/mL for 6-O-MEL and 0.50 ng/mL for S-O-MEL. The intra- and inter-day precision was within 13.5% in terms of relative standard deviation (RSD%) and the accuracy within 13.0% in terms of relative error. This convenient and specific LC-MS/MS method was successfully applied to the pharmacokinetic study of MEL and its metabolites in Beagle dogs after an oral dose of 2.0mg MEL. After ingestion of MEL, S-O-MEL was the predominant component circulating in blood. 6-O-MEL showed similar pharmacokinetic profile to that of MEL. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Methods of analysis by the U.S. Geological Survey National Water Quality Laboratory; determination of dissolved arsenic, boron, lithium, selenium, strontium, thallium, and vanadium using inductively coupled plasma-mass spectrometry

    Science.gov (United States)

    Garbarino, John R.

    1999-01-01

    The inductively coupled plasma?mass spectrometric (ICP?MS) methods have been expanded to include the determination of dissolved arsenic, boron, lithium, selenium, strontium, thallium, and vanadium in filtered, acidified natural water. Method detection limits for these elements are now 10 to 200 times lower than by former U.S. Geological Survey (USGS) methods, thus providing lower variability at ambient concentrations. The bias and variability of the method was determined by using results from spike recoveries, standard reference materials, and validation samples. Spike recoveries at 5 to 10 times the method detection limit and 75 micrograms per liter in reagent-water, surface-water, and groundwater matrices averaged 93 percent for seven replicates, although selected elemental recoveries in a ground-water matrix with an extremely high iron sulfate concentration were negatively biased by 30 percent. Results for standard reference materials were within 1 standard deviation of the most probable value. Statistical analysis of the results from about 60 filtered, acidified natural-water samples indicated that there was no significant difference between ICP?MS and former USGS official methods of analysis.

  12. Analytical method for the determination of various arsenic species in rice, rice food products, apple juice, and other juices by ion chromatography-inductively coupled plasma/mass spectrometry.

    Science.gov (United States)

    Ellingson, David; Zywicki, Richard; Sullivan, Darryl

    2014-01-01

    Recent studies have shown that there are detectable levels of arsenic (As) in rice, rice food products, and apple juice. This has created significant concern to the public, the food industry, and various regulatory bodies. Classic test methods typically measure total As and are unable to differentiate the various As species. Since different As species have greatly different toxicities, an analytical method was needed to separate and quantify the different inorganic and organic species of As. The inorganic species arsenite [As(+3)] and arsenate [As(+5)] are highly toxic. With this in mind, an ion chromatography-inductively coupled plasma (IC-ICP/MS) method was developed and validated for rice and rice food products that can separate and individually measure multiple inorganic and organic species of As. This allows for the evaluation of the safety or risk associated with any product analyzed. The IC-ICP/MS method was validated on rice and rice food products, and it has been used successfully on apple juice. This paper provides details of the validated method as well as some lessons learned during its development. Precision and accuracy data are presented for rice, rice food products, and apple juice.

  13. A simple method using on-line continuous leaching and ion exchange chromatography coupled to inductively coupled plasma mass spectrometry for the speciation analysis of bio-accessible arsenic in rice.

    Science.gov (United States)

    Horner, Nolan S; Beauchemin, Diane

    2012-03-02

    A simple method for the speciation analysis of bio-accessible arsenic (As) in rice was developed using a continuous on-line leaching method to release the bio-accessible fraction. The continuous on-line leaching method has several advantages over commonly used batch methods including quicker and easier sample preparation, reduced risk of contamination and access to real time leaching data. The bio-accessibility of As in the samples was monitored using inductively coupled plasma mass spectrometry (ICP-MS). Results from a certified reference material as well as cooked and uncooked white rice showed that the majority of As was leached by saliva. Results obtained using the continuous on-line leaching method were comparable to those obtained using a batch method. Speciation analysis of the saliva leachate was performed using ion exchange chromatography coupled to ICP-MS. The four most toxic forms of As (As(III), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and As(V)) were clearly separated within 5 min in a single chromatographic run. Over 92% of bio-accessible As in the certified reference material and uncooked white rice sample was in the form of DMA and As(V), whereas it was present as DMA and As(III) in the cooked white rice. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Creatinine, arsenic metabolism, and renal function in an arsenic-exposed population in Bangladesh.

    Science.gov (United States)

    Peters, Brandilyn A; Hall, Megan N; Liu, Xinhua; Neugut, Y Dana; Pilsner, J Richard; Levy, Diane; Ilievski, Vesna; Slavkovich, Vesna; Islam, Tariqul; Factor-Litvak, Pam; Graziano, Joseph H; Gamble, Mary V

    2014-01-01

    Kidney disease is emerging as an arsenic (As)-linked disease outcome, however further evidence of this association is warranted. Our first objective for this paper was to examine the potential renal toxicity of As exposure in Bangladesh. Our second objective relates to examining whether the previously reported positive association between urinary creatinine (uCrn) and As methylation may be explained by renal function. We had hypothesized that these associations relate to supply and demand for s-adenosylmethionine, the methyl donor for both creatine synthesis and As methylation. Alternatively, renal function could influence both As and creatinine excretion, or the As metabolites may influence renal function, which in turn influences uCrn. We conducted a cross-sectional study (N = 478) of adults, composed of a sample recruited in 2001 and a sample recruited in 2003. We assessed renal function using plasma cystatin C, and calculated the estimated glomerular filtration rate (eGFR). Consistent with renal toxicity of As, log-uAs had a marginal inverse association with eGFR in the 2003 sample (b = -5.6, p = 0.07), however this association was not significant in the 2001 sample (b = -1.9, p = 0.24). Adjustment for eGFR did not alter the associations between uCrn and the %uAs metabolites, indicating that GFR does not explain these associations. Increased eGFR was associated with increased odds of having %uInAs >12.2% (2001: OR = 1.01, 95%CI (1.00,1.03); 2003: OR = 1.04, 95%CI (1.01,1.07)). In the 2003 sample only, there was a negative association between eGFR and %uDMA (b = -0.08, p = 0.02). These results may indicate differential effects of renal function on excretion of InAs and DMA. Alternatively, a certain methylation pattern, involving decreased %InAs and increased %DMA, may reduce renal function. Given that these studies were cross-sectional, we cannot distinguish between these two possibilities. Discrepancies between the samples

  15. Arsenic exacerbates atherosclerotic lesion formation and inflammation in ApoE-/- mice

    International Nuclear Information System (INIS)

    Srivastava, Sanjay; Vladykovskaya, Elena N.; Haberzettl, Petra; Sithu, Srinivas D.; D'Souza, Stanley E.; States, J. Christopher

    2009-01-01

    Exposure to arsenic-contaminated water has been shown to be associated with cardiovascular disease, especially atherosclerosis. We examined the effect of arsenic exposure on atherosclerotic lesion formation, lesion composition and nature in ApoE-/- mice. Early post-natal exposure (3-week-old mice exposed to 49 ppm arsenic as NaAsO 2 in drinking water for 7 weeks) increased the atherosclerotic lesion formation by 3- to 5-fold in the aortic valve and the aortic arch, without affecting plasma cholesterol. Exposure to arsenic for 13 weeks (3-week-old mice exposed to 1, 4.9 and 49 ppm arsenic as NaAsO 2 in drinking water) increased the lesion formation and macrophage accumulation in a dose-dependent manner. Temporal studies showed that continuous arsenic exposure significantly exacerbated the lesion formation throughout the aortic tree at 16 and 36 weeks of age. Withdrawal of arsenic for 12 weeks after an initial exposure for 21 weeks (to 3-week-old mice) significantly decreased lesion formation as compared with mice continuously exposed to arsenic. Similarly, adult exposure to 49 ppm arsenic for 24 weeks, starting at 12 weeks of age increased lesion formation by 2- to 3.6-fold in the aortic valve, the aortic arch and the abdominal aorta. Lesions of arsenic-exposed mice displayed a 1.8-fold increase in macrophage accumulation whereas smooth muscle cell and T-lymphocyte contents were not changed. Expression of pro-inflammatory chemokine MCP-1 and cytokine IL-6 and markers of oxidative stress, protein-HNE and protein-MDA adducts were markedly increased in lesions of arsenic-exposed mice. Plasma concentrations of MCP-1, IL-6 and MDA were also significantly elevated in arsenic-exposed mice. These data suggest that arsenic exposure increases oxidative stress, inflammation and atherosclerotic lesion formation.

  16. Binational Arsenic Exposure Survey: Methodology and Estimated Arsenic Intake from Drinking Water and Urinary Arsenic Concentrations

    Directory of Open Access Journals (Sweden)

    Robin B. Harris

    2012-03-01

    Full Text Available The Binational Arsenic Exposure Survey (BAsES was designed to evaluate probable arsenic exposures in selected areas of southern Arizona and northern Mexico, two regions with known elevated levels of arsenic in groundwater reserves. This paper describes the methodology of BAsES and the relationship between estimated arsenic intake from beverages and arsenic output in urine. Households from eight communities were selected for their varying groundwater arsenic concentrations in Arizona, USA and Sonora, Mexico. Adults responded to questionnaires and provided dietary information. A first morning urine void and water from all household drinking sources were collected. Associations between urinary arsenic concentration (total, organic, inorganic and estimated level of arsenic consumed from water and other beverages were evaluated through crude associations and by random effects models. Median estimated total arsenic intake from beverages among participants from Arizona communities ranged from 1.7 to 14.1 µg/day compared to 0.6 to 3.4 µg/day among those from Mexico communities. In contrast, median urinary inorganic arsenic concentrations were greatest among participants from Hermosillo, Mexico (6.2 µg/L whereas a high of 2.0 µg/L was found among participants from Ajo, Arizona. Estimated arsenic intake from drinking water was associated with urinary total arsenic concentration (p < 0.001, urinary inorganic arsenic concentration (p < 0.001, and urinary sum of species (p < 0.001. Urinary arsenic concentrations increased between 7% and 12% for each one percent increase in arsenic consumed from drinking water. Variability in arsenic intake from beverages and urinary arsenic output yielded counter intuitive results. Estimated intake of arsenic from all beverages was greatest among Arizonans yet participants in Mexico had higher urinary total and inorganic arsenic concentrations. Other contributors to urinary arsenic concentrations should be evaluated.

  17. Raman spectra of thiolated arsenicals with biological importance.

    Science.gov (United States)

    Yang, Mingwei; Sun, Yuzhen; Zhang, Xiaobin; McCord, Bruce; McGoron, Anthony J; Mebel, Alexander; Cai, Yong

    2018-03-01

    Surface enhanced Raman scattering (SERS) has great potential as an alternative tool for arsenic speciation in biological matrices. SERS measurements have advantages over other techniques due to its ability to maintain the integrity of arsenic species and its minimal requirements for sample preparation. Up to now, very few Raman spectra of arsenic compounds have been reported. This is particularly true for thiolated arsenicals, which have recently been found to be widely present in humans. The lack of data for Raman spectra in arsenic speciation hampers the development of new tools using SERS. Herein, we report the results of a study combining the analysis of experimental Raman spectra with that obtained from density functional calculations for some important arsenic metabolites. The results were obtained with a hybrid functional B3LYP approach using different basis sets to calculate Raman spectra of the selected arsenicals. By comparing experimental and calculated spectra of dimethylarsinic acid (DMA V ), the basis set 6-311++G** was found to provide computational efficiency and precision in vibrational frequency prediction. The Raman frequencies for the rest of organoarsenicals were studied using this basis set, including monomethylarsonous acid (MMA III ), dimethylarsinous acid (DMA III ), dimethylmonothioarinic acid (DMMTA V ), dimethyldithioarsinic acid (DMDTA V ), S-(Dimethylarsenic) cysteine (DMA III (Cys)) and dimethylarsinous glutathione (DMA III GS). The results were compared with fingerprint Raman frequencies from As─O, As─C, and As─S obtained under different chemical environments. These fingerprint vibrational frequencies should prove useful in future measurements of different species of arsenic using SERS. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Environmental biochemistry of arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Tamaki, S.; Frankenberger, W.T. Jr. (Department of Soil and Environmental Sciences, University of California, Riverside (United States))

    1992-01-01

    Microorganisms are involved in the redistribution and global cycling of arsenic. Arsenic can accumulate and can be subject to various biotransformations including reduction, oxidation, and methylation. Bacterial methylation of inorganic arsenic is coupled to the methane biosynthetic pathway in methanogenic bacteria under anaerobic conditions and may be a mechanism for arsenic detoxification. The pathway proceeds by reduction of arsenate to arsenite followed by methylation to dimethylarsine. Fungi are also able to transform inorganic and organic arsenic compounds into volatile methylarsines. The pathway proceeds aerobically by arsenate reduction to arsenite followed by several methylation steps producing trimethylarsine. Volatile arsine gases are very toxic to mammals because they destroy red blood cells (LD50 in rats; 3.0 mg kg-1). Further studies are needed on dimethylarsine and trimethylarsine toxicity tests through inhalation of target animals. Marine algae transform arsenate into non-volatile methylated arsenic compounds (methanearsonic and dimethylarsinic acids) in seawater. This is considered to be a beneficial step not only to the primary producers, but also to the higher trophic levels, since non-volatile methylated arsenic is much less toxic to marine invertebrates. Freshwater algae like marine algae synthesize lipid-soluble arsenic compounds and do not produce volatile methylarsines. Aquatic plants also synthesize similar lipid-soluble arsenic compounds. In terrestrial plants, arsenate is preferentially taken up 3 to 4 times the rate of arsenite. In the presence of phosphate, arsenate uptake is inhibited while in the presence of arsenate, phosphate uptake is only slightly inhibited. There is a competitive interaction between arsenate and phosphate for the same uptake system in terrestrial plants.

  19. Inhibition of insulin-dependent glucose uptake by trivalent arsenicals: possible mechanism of arsenic-induced diabetes

    International Nuclear Information System (INIS)

    Walton, Felecia S.; Harmon, Anne W.; Paul, David S.; Drobna, Zuzana; Patel, Yashomati M.; Styblo, Miroslav

    2004-01-01

    Chronic exposures to inorganic arsenic (iAs) have been associated with increased incidence of noninsulin (type-2)-dependent diabetes mellitus. Although mechanisms by which iAs induces diabetes have not been identified, the clinical symptoms of the disease indicate that iAs or its metabolites interfere with insulin-stimulated signal transduction pathway or with critical steps in glucose metabolism. We have examined effects of iAs and methylated arsenicals that contain trivalent or pentavalent arsenic on glucose uptake by 3T3-L1 adipocytes. Treatment with inorganic and methylated pentavalent arsenicals (up to 1 mM) had little or no effect on either basal or insulin-stimulated glucose uptake. In contrast, trivalent arsenicals, arsenite (iAs III ), methylarsine oxide (MAs III O), and iododimethylarsine (DMAs III O) inhibited insulin-stimulated glucose uptake in a concentration-dependent manner. Subtoxic concentrations of iAs III (20 μM), MAs III O (1 μM), or DMAs III I (2 μM) decreased insulin-stimulated glucose uptake by 35-45%. Basal glucose uptake was significantly inhibited only by cytotoxic concentrations of iAs III or MAs III O. Examination of the components of the insulin-stimulated signal transduction pathway showed that all trivalent arsenicals suppressed expression and possibly phosphorylation of protein kinase B (PKB/Akt). The concentration of an insulin-responsive glucose transporter (GLUT4) was significantly lower in the membrane region of 3T3-L1 adipocytes treated with trivalent arsenicals as compared with untreated cells. These results suggest that trivalent arsenicals inhibit insulin-stimulated glucose uptake by interfering with the PKB/Akt-dependent mobilization of GLUT4 transporters in adipocytes. This mechanism may be, in part, responsible for the development of type-2 diabetes in individuals chronically exposed to iAs

  20. Online restricted-access material combined with high-performance liquid chromatography and tandem mass spectrometry for the simultaneous determination of vanillin and its vanillic acid metabolite in human plasma.

    Science.gov (United States)

    Li, De-Qiang; Zhang, Zhi-Qing; Yang, Xiu-Ling; Zhou, Chun-Hua; Qi, Jin-Long

    2016-09-01

    An automated online solid-phase extraction with restricted-access material combined with high-performance liquid chromatography and tandem mass spectrometry was developed and validated for the simultaneous quantification of vanillin and its vanillic acid metabolite in human plasma. After protein precipitation by methanol, which contained the internal standards, the supernatant of plasma samples was injected to the system, the endogenous large molecules were flushed out, and target analytes were trapped and enriched on the adsorbent, resulting in a minimization of sample complexity and ion suppression effects. Calibration curves were linear over the concentrations of 5-1000 ng/mL for vanillin and 10-5000 ng/mL for vanillic acid with a coefficient of determination >0.999 for the determined compounds. The lower limits of quantification of vanillin and vanillic acid were 5.0 and 10.0 ng/mL, respectively. The intra- and inter-run precisions expressed as the relative standard deviation were 2.6-8.6 and 3.2-10.2%, respectively, and the accuracies expressed as the relative error were in the range of -6.1 to 7.3%. Extraction recoveries of analytes were between 89.5 and 97.4%. There was no notable matrix effect for any analyte concentration. The developed method was proved to be sensitive, repeatable, and accurate for the quantification of vanillin and its vanillic acid metabolite in human plasma. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Simultaneous determination of chloroquine and its three metabolites in human plasma, whole blood and urine by ion-pair high-performance liquid chromatography.

    Science.gov (United States)

    Houzé, P; de Reynies, A; Baud, F J; Benatar, M F; Pays, M

    1992-02-14

    A method was developed for the separation and measurement of chloroquine and three metabolites (desethylchloroquine, bisdesethylchloroquine and 4-amino-7-chloroquinoline) in biological samples by ion-pair high-performance liquid chromatography with UV detection. The method uses 2,3-diaminoaphthalene as an internal standard and provides a limit of detection between 1 and 2 ng/ml for chloroquine and its metabolites. The assay was linear in the range 12.5-250 ng/ml and the analytical recovery and reproducibility were sufficient. The assay was applied to the analysis of biological samples from a patient undergoing chloroquine chemoprophylaxis and a patient who had ingested chloroquine in a suicide attempt.

  2. Development and Validation of a UPLC-MS/MS and UPLC-HR-MS Method for the Determination of Fumonisin B1 and Its Hydrolysed Metabolites and Fumonisin B2 in Broiler Chicken Plasma

    Directory of Open Access Journals (Sweden)

    Siegrid De Baere

    2018-01-01

    Full Text Available A sensitive and specific method for the quantitative determination of Fumonisin B1 (FB1, its partially hydrolysed metabolites pHFB1a+b and hydrolysed metabolite HFB1, and Fumonisin B2 (FB2 in broiler chicken plasma using ultra-performance liquid chromatography combined with tandem mass spectrometry (UPLC-MS/MS was developed. The sample preparation was rapid, straightforward and consisted of a deproteinization and phospholipid removal step using an Oasis® OstroTM 96-well plate. Chromatography was performed on an Acquity HSS-T3 column, using 0.3% formic acid and 10 mM ammonium formate in water, and acetonitrile as mobile phases. The MS/MS instrument was operated in the positive electrospray ionization mode and the two multiple reaction monitoring transitions were monitored for each component for quantification and identification, respectively. The method was validated in-house: matrix-matched calibration graphs were prepared and good linearity (r ≥ 0.99 was achieved over the concentration ranges tested (1–500 ng/mL for FB1 and FB2; 0.86–860 ng/mL for pHFB1a; 0.72–1430 ng/mL for pHFB1b and 2.5–2500 ng/mL for HFB1. Limits of quantification (LOQ and detection (LOD in plasma ranged between 0.72 to 2.5 ng/mL and 0.03 to 0.17 ng/mL, respectively. The results for the within-day and between-day precision and accuracy fell within the specified ranges. Moreover, the method was transferred to an UPLC high-resolution mass spectrometry (HR-MS instrument in order to determine potential metabolites of HFB1, such as N-acyl-HFB1s and phase II metabolites. The method has been successfully applied to investigate the toxicokinetics and biotransformation of HFB1 in broiler chickens.

  3. Effects of Cytochrome P450 (CYP) 2C19 Genotypes on Steady-State Plasma Concentrations of Escitalopram and its Desmethyl Metabolite in Japanese Patients With Depression.

    Science.gov (United States)

    Tsuchimine, Shoko; Ochi, Shinichiro; Tajiri, Misuzu; Suzuki, Yutaro; Sugawara, Norio; Inoue, Yoshimasa; Yasui-Furukori, Norio

    2018-06-01

    Plasma concentrations of the S-enantiomer of citalopram were different between extensive and poor CYP2C19 metabolizers in healthy subjects and depressed patients. However, most studies applied dose-corrected concentrations. Thus, we studied the effects of polymorphisms of the CYP2C19 gene on raw plasma drug concentrations in Japanese patients with depression. Subjects in this study consisted of 412 depressed patients receiving 5, 10, 15, or 20 mg of escitalopram once a day. Plasma concentrations of escitalopram and desmethylescitalopram were quantified using HPLC. CYP2C19 genotypes were identified using polymerase chain reaction methods. There were no differences in the steady-state plasma concentrations of escitalopram or desmethylescitalopram in each dose group (5, 10, 15, or 20 mg of escitalopram) among CYP2C19 genotype groups. However, 1-way analysis of variance showed significant effects of CYP2C19 genotypes on the dose-adjusted plasma concentration of escitalopram but not in the dose-adjusted plasma concentration of desmethylescitalopram. Analysis of covariance including age, sex, and body weight showed significant effects of CYP2C19 genotypes on the dose-adjusted plasma concentration of escitalopram and the ratio of desmethylescitalopram to escitalopram. These findings suggest that the CYP2C19 variants are associated with steady-state plasma concentrations of escitalopram to some extent but are not associated with desmethylescitalopram.

  4. Quantification of low molecular weight selenium metabolites in human plasma after treatment with selenite in pharmacological doses by LC-ICP-MS

    DEFF Research Database (Denmark)

    Flouda, Konstantina; Dersch, Julie Maria; Gabel-Jensen, Charlotte

    2016-01-01

    The paper presents an analytical method for quantification of low molecular weight (LMW) selenium compounds in human plasma based on liquid chromatography inductively coupled plasma mass spectrometry (LC-ICP-MS) and post column isotope dilution-based quantification. Prior to analysis, samples were...

  5. Arsenic speciation results

    Data.gov (United States)

    U.S. Environmental Protection Agency — Linear combination fitting results of synchrotron data to determine arsenic speciation in soil samples. This dataset is associated with the following publication:...

  6. Arsenic Trioxide Injection

    Science.gov (United States)

    ... people who have not been helped by other types of chemotherapy or whose condition has improved but then worsened following treatment with other types of chemotherapy. Arsenic trioxide is in a class of medications ...

  7. Paper on Arsenic

    African Journals Online (AJOL)

    Hiren

    The current study was undertaken to determine the effects of arsenic on ... concentration caused reduction in plant growth along with induction of few antioxidants. ... esculentum, a herbaceous monocot plant, towards reactive oxygen species.

  8. Effects of Abandoned Arsenic Mine on Water Resources Pollution in North West of Iran

    Directory of Open Access Journals (Sweden)

    Esmail Fatehifar

    2011-07-01

    Full Text Available Background: Pollution due to mining activities could have an important role in health andwelfare of people who are living in mining area. When mining operation finishes, environmentof mining area can be influenced by related pollution e.g. heavy metals emission to waterresources. The present study was aimed to evaluate Valiloo abandoned arsenic mine effectson drinking water resources quality and possible health effects on the residents of miningarea in the North West of Iran.Methods: Water samples and some limited composite wheat samples in downstream of miningarea were collected. Water samples were analyzed for chemical parameters according tostandard methods. For determination of arsenic in water samples, Graphite Furnace AtomicAbsorption Spectrometric Method (GFAAS and for wheat samples X – Ray Fluorescence(XRF and Inductively Coupled Plasma Method (ICP were used. Information about possiblehealth effects due to exposure to arsenic was collected through interviews in studied villagesand health center of Herris City.Results: The highest concentrations of arsenic were measured near the mine (as high as 2000μg/L in Valiloo mine opening water. With increasing distance from the mine, concentrationwas decreased. Arsenic was not detectable in any of wheat samples. Fortunately, no healtheffects had been reported between residents of studied area due to exposure to arsenic.Conclusion: Valiloo abandoned arsenic mine has caused release of arsenic to the around environmentof the mine, so arsenic concentration has been increased in the groundwater andalso downstream river that requires proper measures to mitigate spread of arsenic.

  9. [Qualitative and quantitative analysis of amygdalin and its metabolite prunasin in plasma by ultra-high performance liquid chromatography-tandem quadrupole time of flight mass spectrometry and ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry].

    Science.gov (United States)

    Gao, Meng; Wang, Yuesheng; Wei, Huizhen; Ouyang, Hui; He, Mingzhen; Zeng, Lianqing; Shen, Fengyun; Guo, Qiang; Rao, Yi

    2014-06-01

    A method was developed for the determination of amygdalin and its metabolite prunasin in rat plasma after intragastric administration of Maxing shigan decoction. The analytes were identified by ultra-high performance liquid chromatography-tandem quadrupole time of flight mass spectrometry and quantitatively determined by ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry. After purified by liquid-liquid extraction, the qualitative analysis of amygdalin and prunasin in the plasma sample was performed on a Shim-pack XR-ODS III HPLC column (75 mm x 2.0 mm, 1.6 microm), using acetonitrile-0.1% (v/v) formic acid aqueous solution. The detection was performed on a Triple TOF 5600 quadrupole time of flight mass spectrometer. The quantitative analysis of amygdalin and prunasin in the plasma sample was performed by separation on an Agilent C18 HPLC column (50 mm x 2.1 mm, 1.7 microm), using acetonitrile-0.1% (v/v) formic acid aqueous solution. The detection was performed on an AB Q-TRAP 4500 triple quadrupole mass spectrometer utilizing electrospray ionization (ESI) interface operated in negative ion mode and multiple-reaction monitoring (MRM) mode. The qualitative analysis results showed that amygdalin and its metabolite prunasin were detected in the plasma sample. The quantitative analysis results showed that the linear range of amygdalin was 1.05-4 200 ng/mL with the correlation coefficient of 0.999 0 and the linear range of prunasin was 1.25-2 490 ng/mL with the correlation coefficient of 0.997 0. The method had a good precision with the relative standard deviations (RSDs) lower than 9.20% and the overall recoveries varied from 82.33% to 95.25%. The limits of detection (LODs) of amygdalin and prunasin were 0.50 ng/mL. With good reproducibility, the method is simple, fast and effective for the qualitative and quantitative analysis of the amygdalin and prunasin in plasma sample of rats which were administered by Maxing shigan decoction.

  10. Determination of total arsenic and arsenic species in drinking water, surface water, wastewater, and snow from Wielkopolska, Kujawy-Pomerania, and Lower Silesia provinces, Poland.

    Science.gov (United States)

    Komorowicz, Izabela; Barałkiewicz, Danuta

    2016-09-01

    Arsenic is a ubiquitous element which may be found in surface water, groundwater, and drinking water. In higher concentrations, this element is considered genotoxic and carcinogenic; thus, its level must be strictly controlled. We investigated the concentration of total arsenic and arsenic species: As(III), As(V), MMA, DMA, and AsB in drinking water, surface water, wastewater, and snow collected from the provinces of Wielkopolska, Kujawy-Pomerania, and Lower Silesia (Poland). The total arsenic was analyzed by inductively coupled plasma mass spectrometry (ICP-MS), and arsenic species were analyzed with use of high-performance liquid chromatography inductively coupled plasma mass spectrometry (HPLC/ICP-MS). Obtained results revealed that maximum total arsenic concentration determined in drinking water samples was equal to 1.01 μg L(-1). The highest concentration of total arsenic in surface water, equal to 3778 μg L(-1) was determined in Trująca Stream situated in the area affected by geogenic arsenic contamination. Total arsenic concentration in wastewater samples was comparable to those determined in drinking water samples. However, significantly higher arsenic concentration, equal to 83.1 ± 5.9 μg L(-1), was found in a snow sample collected in Legnica. As(V) was present in all of the investigated samples, and in most of them, it was the sole species observed. However, in snow sample collected in Legnica, more than 97 % of the determined concentration, amounting to 81 ± 11 μg L(-1), was in the form of As(III), the most toxic arsenic species.

  11. Enhancements of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism and carcinogenic risk via NNK/arsenic interaction

    International Nuclear Information System (INIS)

    Lee, H.-L.; Chang, Louis W.; Wu, J.-P.; Ueng, Y.-F.; Tsai, M.-H.; Hsieh, Dennis Paul Hsientang; Lin Pinpin

    2008-01-01

    Epidemiological studies indicated an enhancement of cigarette smoke-induced carcinogenicity, including hepatocellular carcinoma, by arsenic. We believe that arsenic will enhance the expression of hepatic CYP2A enzyme and NNK metabolism (a cigarette smoke component), thus its metabolites, and carcinogenic DNA adducts. Male ICR mice were exposed to NNK (0.5 mg/mouse) and sodium arsenite (0, 10, or 20 mg/kg) daily via gavaging for 10 days and their urine was collected at day 10 for NNK metabolite analysis. Liver samples were also obtained for CYP2A enzyme and DNA adducts evaluations. Both the cyp2a4/5 mRNA levels and the CYP2A enzyme activity were significantly elevated in arsenic-treated mice liver. Furthermore, urinary NNK metabolites in NNK/arsenic co-treated mice also increased compared to those treated with NNK alone. Concomitantly, DNA adducts (N 7 -methylguanine and O 6 -methylguanine) were significantly elevated in the livers of mice co-treated with NNK and arsenic. Our findings provide clear evidence that arsenic increased NNK metabolism by up-regulation of CYP2A expression and activity leading to an increased NNK metabolism and DNA adducts (N 7 -methylguanine and O 6 -methylguanine). These findings suggest that in the presence of arsenic, NNK could induce greater DNA adducts formation in hepatic tissues resulting in higher carcinogenic potential

  12. Sensitive determination of three aconitum alkaloids and their metabolites in human plasma by matrix solid-phase dispersion with vortex-assisted dispersive liquid-liquid microextraction and HPLC with diode array detection.

    Science.gov (United States)

    Wang, Xiaozhong; Li, Xuwen; Li, Lanjie; Li, Min; Liu, Ying; Wu, Qian; Li, Peng; Jin, Yongri

    2016-05-01

    A simple and sensitive method for determination of three aconitum alkaloids and their metabolites in human plasma was developed using matrix solid-phase dispersion combined with vortex-assisted dispersive liquid-liquid microextraction and high-performance liquid chromatography with diode array detection. The plasma sample was directly purified by matrix solid-phase dispersion and the eluate obtained was concentrated and further clarified by vortex-assisted dispersive liquid-liquid microextraction. Some important parameters affecting the extraction efficiency, such as type and amount of dispersing sorbent, type and volume of elution solvent, type and volume of extraction solvent, salt concentration as well as sample solution pH, were investigated in detail. Under optimal conditions, the proposed method has good repeatability and reproducibility with intraday and interday relative standard deviations lower than 5.44 and 5.75%, respectively. The recoveries of the aconitum alkaloids ranged from 73.81 to 101.82%, and the detection limits were achieved within the range of 1.6-2.1 ng/mL. The proposed method offered the advantages of good applicability, sensitivity, simplicity, and feasibility, which makes it suitable for the determination of trace amounts of aconitum alkaloids in human plasma samples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Development and validation of a high performance liquid chromatographic method for the determination of oxcarbazepine and its main metabolites in human plasma and cerebrospinal fluid and its application to pharmacokinetic study.

    Science.gov (United States)

    Kimiskidis, Vasilios; Spanakis, Marios; Niopas, Ioannis; Kazis, Dimitrios; Gabrieli, Chrysi; Kanaze, Feras Imad; Divanoglou, Daniil

    2007-01-17

    An isocratic reversed-phase HPLC-UV procedure for the determination of oxcarbazepine and its main metabolites 10-hydroxy-10,11-dihydrocarbamazepine and 10,11-dihydroxy-trans-10,11-dihydrocarbamazepine in human plasma and cerebrospinal fluid has been developed and validated. After addition of bromazepam as internal standard, the analytes were isolated from plasma and cerebrospinal fluid by liquid-liquid extraction. Separation was achieved on a X-TERRA C18 column using a mobile phase composed of 20 mM KH(2)PO(4), acetonitrile, and n-octylamine (76:24:0.05, v/v/v) at 40 degrees C and detected at 237 nm. The described assay was validated in terms of linearity, accuracy, precision, recovery and lower limit of quantification according to the FDA validation guidelines. Calibration curves were linear with a coefficient of variation (r) greater than 0.998. Accuracy ranged from 92.3% to 106.0% and precision was between 2.3% and 8.2%. The method has been applied to plasma and cerebrospinal fluid samples obtained from patients treated with oxcarbazepine, both in monotherapy and adjunctive therapy.

  14. Identification of an S-adenosylmethionine (SAM) dependent arsenic methyltransferase in Danio rerio

    Energy Technology Data Exchange (ETDEWEB)

    Hamdi, Mohamad [Department of Biological Sciences, Oakland University, Rochester, MI 48309 (United States); Yoshinaga, Masafumi; Packianathan, Charles; Qin, Jie [Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, FL33199 (United States); Hallauer, Janell; McDermott, Joseph R. [Department of Biological Sciences, Oakland University, Rochester, MI 48309 (United States); Yang, Hung-Chi [Department of Medical Biotechnology and Laboratory Sciences, Chang-Gung University, Tao-Yuan, Kwei-San 333, Taiwan (China); Tsai, Kan-Jen [School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China); Liu, Zijuan, E-mail: liu2345@oakland.edu [Department of Biological Sciences, Oakland University, Rochester, MI 48309 (United States)

    2012-07-15

    Arsenic methylation is an important cellular metabolic process that modulates arsenic toxicity and carcinogenicity. Biomethylation of arsenic produces a series of mono-, di- and tri-methylated arsenic metabolites that can be detected in tissues and excretions. Here we report that zebrafish exposed to arsenite (As{sup III}) produces organic arsenicals, including MMA{sup III}, MMA{sup V} and DMA{sup V} with characteristic tissue ratios, demonstrating that an arsenic methylation pathway exists in zebrafish. In mammals, cellular inorganic arsenic is methylated by a SAM-dependent arsenic methyltransferase, AS3MT. A zebrafish arsenic methyltransferase homolog, As3mt, was identified by sequence alignment. Western blotting analysis showed that As3mt was universally expressed in zebrafish tissues. Prominent expression in liver and intestine correlated with methylated arsenic metabolites detected in those tissues. As3mt was expressed in and purified from Escherichia coli for in vitro functional studies. Our results demonstrated that As3mt methylated As{sup III} to DMA{sup V} as an end product and produced MMA{sup III} and MMA{sup V} as intermediates. The activity of As3mt was inhibited by elevated concentrations of the substrate As{sup III} as well as the metalloid selenite, which is a well-known antagonistic micronutrient of arsenic toxicity. The activity As3mt was abolished by substitution of either Cys160 or Cys210, which corresponds to conserved cysteine residues in AS3MT homologs, suggesting that they are involved in catalysis. Expression in zebrafish of an enzyme that has a similar function to human and rodent orthologs in catalyzing intracellular arsenic biomethylation validates the applicability of zebrafish as a valuable vertebrate model for understanding arsenic-associated diseases in humans. -- Highlights: ► Zebrafish methylated As{sup III} to MMA{sup III}, MMA{sup V} and DMA{sup V}. ► A zebrafish arsenic methyltransferase (As3mt) was purified in E. coli.

  15. HPLC-ICP-MS speciation analysis and risk assessment of arsenic in Cordyceps sinensis.

    Science.gov (United States)

    Zuo, Tian-Tian; Li, Yao-Lei; Jin, Hong-Yu; Gao, Fei; Wang, Qi; Wang, Ya-Dan; Ma, Shuang-Cheng

    2018-01-01

    Cordyceps sinensis , one of the most valued traditional herbal medicines in China, contains high amount of arsenic. Considering the adverse health effects of arsenic, this is of particular concern. The aim of this study was to determine and analyze arsenic speciation in C. sinensis , and to measure the associated human health risks. We used microwave extraction and high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry to determine and analyze the arsenic content in C. sinensis , and measured the associated human health risks according to the hazard index (HI), lifetime cancer risk (CR), and target hazard quotient (THQ). The main arsenic speciation in C. sinensis were not the four organic arsenic compounds, including dimethyl arsenic, monomethyl arsenic, arsenobetaine, and arsenocholine, but comprised inorganic arsenic and other unknown risk arsenic compounds. HI scores indicated that the risk of C. sinensis was acceptable. CR results suggested that the cancer risk was greater than the acceptable lifetime risk of 10 -5 , even at low exposure levels. THQ results indicated that at the exposure level  3.0 months/year, the systemic effects of the arsenic in C. sinensis was of great concern. The arsenic in C. sinensis might not be free of risks. The suggested C. sinensis consumption rate of 2.0 months/year provided important insights into the ways by which to minimize potential health risks. Our study not only played the role of "cast a brick to attract jade" by which to analyze arsenic speciation in C. sinensis but also offered a promising strategy of risk assessment for harmful residues in traditional herbal medicines.

  16. Arsenic (Environmental Health Student Portal)

    Science.gov (United States)

    ... Water Waterborne Diseases & Illnesses Water Cycle Water Treatment Videos Games Experiments For Teachers Home Chemicals Arsenic Print this ... human activities, such as mining, farming, and other industries. This can be dangerous, because arsenic is poisonous ...

  17. Effect of Terminalia arjuna bark powder on some diagnostic enzymes in buffalo (Bubalus bubalis ingesting arsenic contaminated water and fodder

    Directory of Open Access Journals (Sweden)

    Subrat Kumar Dash

    2016-10-01

    Full Text Available Aim: The study investigated the effect of Terminalia arjuna bark powder on some diagnostic enzymes related to hepatic and muscle function in buffaloes ingesting arsenic contaminated water and fodder in an arsenic affected area. Materials and Methods: A total of 25 samples of tube well water, fodder and buffalo blood were collected through a survey from arsenic contaminated areas and 20 samples from the uncontaminated, i.e., control areas of Ludhiana district, Punjab for determination of arsenic concentration. A total of 30 buffaloes (selected from above 45 animals were divided into three groups of 10 each on the basis of blood arsenic level, viz., control group: Clinically healthy buffaloes from the uncontaminated area with the blood arsenic level within the normal limit (0-0.05 ppm; Arsenic exposed group: Buffaloes exposed to arsenic through intake of contaminated water and fodder in the arsenic affected area with the blood arsenic level above the normal limit of 0-0.05 ppm; treatment group: Arsenic exposed buffaloes treated with T. arjuna bark powder orally at 42 mg/kg b.w. OD for 30 days. Single blood samples were collected from control and arsenic exposed groups. Blood samples from the treatment group were collected on 0, 15th, and 30th day of treatment along with one sample on the 45th day, i.e., after withdrawal of treatment. Activities of alkaline phosphatase (ALP, gamma-glutamyl transferase (GGT, lactate dehydrogenase (LDH, and creatine kinase (CK were assayed in plasma. Results: Significantly (p<0.05 higher arsenic concentration was observed in tube well water, fodder and buffalo blood samples collected from the arsenic contaminated area. A significant positive correlation was noticed between arsenic concentrations of tube well water, fodder and untreated buffalo blood samples, collected from the arsenic affected area. ALP, GGT, LDH, and CK activities were significantly (p<0.05 increased in the arsenic exposed buffaloes compared to

  18. Biomarkers of exposure, effect, and susceptibility of arsenic-induced health hazards in Taiwan

    International Nuclear Information System (INIS)

    Chen, C.-J.; Hsu, L.-I; Wang, C.-H.

    2005-01-01

    Long-term exposure to inorganic arsenic from drinking water has been documented to induce cancers and vascular diseases in a dose-response relationship. A series of molecular environmental epidemiological studies have been carried out to elucidate biomarkers of exposure, effect, and susceptibility for arsenic-related health hazards in Taiwan. Arsenic levels in urine, hair, and nail are biomarkers for short-term (<1 year) internal dose, skin hyperpigmentation and palmoplantar hyperkeratosis are for long-term (many years) internal dose, and percentage of monomethylarsonic acid in total metabolites of inorganic arsenic in urine may be considered as an exposure marker for biologically effective dose. The biomarkers of early biological effects of ingested inorganic arsenic included blood levels of reactive oxidants and anti-oxidant capacity, genetic expression of inflammatory molecules, as well as cytogenetic changes including sister chromatid exchange, micronuclei, and chromosome aberrations of peripheral lymphocytes. Both mutation type and hot spots of p53 gene were significantly different in arsenic-induced and non-arsenic-induced TCCs. The frequency of chromosomal imbalances analyzed by comparative genomic hybridization and the frequency of loss of heterozygosity were significantly higher in arsenic-induced TCC than non-arsenic-induced TCC at specific sites. Biomarkers of susceptibility to arsenic-induced health hazards included genetic polymorphisms of enzymes involved in xenobiotic metabolism, DNA repair, and oxidative stress, as well as serum level of carotenoids. Gene-gene and gene-environment interactions are involved in arsenic-induced health hazards through toxicological mechanisms including genomic instability and oxidative stress

  19. Acute and chronic arsenic toxicity

    OpenAIRE

    Ratnaike, R

    2003-01-01

    Arsenic toxicity is a global health problem affecting many millions of people. Contamination is caused by arsenic from natural geological sources leaching into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Arsenic is present as a contaminant in many traditional remedies. Arsenic trioxide is now used to treat acute promyelocytic leukaemia. Absorption occurs predominantly from ingestion from the small intestine, though minimal absorption o...

  20. Development and validation of a rapid HPLC- fluorescence method for simultaneous determination of venlafaxine and its major metabolites in human plasma

    Directory of Open Access Journals (Sweden)

    Y.H Ardakani

    2010-06-01

    Full Text Available "n Background and the purpose of the study:To develop a simple, rapid and accurate HPLC method for the measurement of the venlafaxine and its main metabolites, O-desmethylvenlafaxine and O,N-didesmethylvenlafaxine in pharmacokinetic studies and therapeutic drug monitoring.Method: Chromatographic separation was achieved with a ChromolithTM Performance RP-18e 100 mm×4.6 mm column equipped with a Fluorescence detectore (λex 200 nm/λem 300 nm The mobile phase of methanol:water (35:65, v/v adjusted to pH 2.5 by phosphoric acid was passed through the column in an isocratic mode at flow rate of 2 ml/min. The sample preparation involved a simple, one-step, extraction with ethyl acetate. "nResults:The calibration curves were linear in the concentration range of 1-300 ng/ml for all analytes (r2 > 0.998. The lower limit of quantification was 1 ng/ml for all analytes. Within and between day precisions in the measurement of quality control (QC of samples were in the range of 1.8-14.1% for all analytes. Conclusion:The developed procedure was used to assess the pharmacokinetics of venlafaxine and its main metabolites following oral administration of 75 mg venlafaxine to a healthy subject.

  1. Detecting beer intake by unique metabolite patterns

    DEFF Research Database (Denmark)

    Gürdeniz, Gözde; Jensen, Morten Georg; Meier, Sebastian

    2016-01-01

    Evaluation of health related effects of beer intake is hampered by the lack of accurate tools for assessing intakes (biomarkers). Therefore, we identified plasma and urine metabolites associated with recent beer intake by untargeted metabolomics and established a characteristic metabolite pattern...... representing raw materials and beer production as a qualitative biomarker of beer intake. In a randomized, crossover, single-blinded meal study (MSt1) 18 participants were given one at a time four different test beverages: strong, regular and non-alcoholic beers and a soft drink. Four participants were...... assigned to have two additional beers (MSt2). In addition to plasma and urine samples, test beverages, wort and hops extract were analyzed by UPLC-QTOF. A unique metabolite pattern reflecting beer metabolome, including metabolites derived from beer raw material (i.e. N-methyl tyramine sulfate and the sum...

  2. Speciated arsenic in air: measurement methodology and risk assessment considerations.

    Science.gov (United States)

    Lewis, Ari S; Reid, Kim R; Pollock, Margaret C; Campleman, Sharan L

    2012-01-01

    Accurate measurement of arsenic (As) in air is critical to providing a more robust understanding of arsenic exposures and associated human health risks. Although there is extensive information available on total arsenic in air, less is known on the relative contribution of each arsenic species. To address this data gap, the authors conducted an in-depth review of available information on speciated arsenic in air. The evaluation included the type of species measured and the relative abundance, as well as an analysis of the limitations of current analytical methods. Despite inherent differences in the procedures, most techniques effectively separated arsenic species in the air samples. Common analytical techniques such as inductively coupled plasma mass spectrometry (ICP-MS) and/or hydride generation (HG)- or quartz furnace (GF)-atomic absorption spectrometry (AAS) were used for arsenic measurement in the extracts, and provided some of the most sensitive detection limits. The current analysis demonstrated that, despite limited comparability among studies due to differences in seasonal factors, study duration, sample collection methods, and analytical methods, research conducted to date is adequate to show that arsenic in air is mainly in the inorganic form. Reported average concentrations of As(III) and As(V) ranged up to 7.4 and 10.4 ng/m3, respectively, with As(V) being more prevalent than As(III) in most studies. Concentrations of the organic methylated arsenic compounds are negligible (in the pg/m3 range). However because of the variability in study methods and measurement methodology, the authors were unable to determine the variation in arsenic composition as a function of source or particulate matter (PM) fraction. In this work, the authors include the implications of arsenic speciation in air on potential exposure and risks. The authors conclude that it is important to synchronize sample collection, preparation, and analytical techniques in order to generate

  3. Simultaneous determination of asperosaponin VI and its active metabolite hederagenin in rat plasma by liquid chromatography-tandem mass spectrometry with positive/negative ion-switching electrospray ionization and its application in pharmacokinetic study.

    Science.gov (United States)

    Zhu, He; Ding, Li; Shakya, Shailendra; Qi, Xiemin; Hu, Linlin; Yang, Xiaolin; Yang, Zhonglin

    2011-11-15

    A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method operated in the positive/negative electrospray ionization (ESI) switching mode has been developed and validated for the simultaneous determination of asperosaponin VI and its active metabolite hederagenin in rat plasma. After addition of internal standards diazepam (for asperosaponin VI) and glycyrrhetic acid (for hederagenin), the plasma sample was deproteinized with acetonitrile, and separated on a reversed phase C18 column with a mobile phase of methanol (solvent A)-0.05% glacial acetic acid containing 10 mM ammonium acetate and 30 μM sodium acetate (solvent B) using gradient elution. The detection of target compounds was done in multiple reaction monitoring (MRM) mode using a tandem mass spectrometry equipped with positive/negative ion-switching ESI source. At the first segment, the MRM detection was operated in the positive ESI mode using the transitions of m/z 951.5 ([M+Na](+))→347.1 for asperosaponin VI and m/z 285.1 ([M+H](+))→193.1 for diazepam for 4 min, then switched to the negative ESI mode using the transitions of m/z 471.3 ([M-H](-))→471.3 for hederagenin and m/z 469.4 ([M-H](-))→425.4 for glycyrrhetic acid, respectively. The sodiated molecular ion [M+Na](+) at m/z 951.5 was selected as the precursor ion for asperosaponin VI, since it provided better sensitivity compared to the deprotonated and protonated molecular ions. Sodium acetate was added to the mobile phase to make sure that abundant amount of the sodiated molecular ion of asperosaponin VI could be produced, and more stable and intensive mass response of the product ion could be obtained. For the detection of hederagenin, since all of the mass responses of the fragment ions were very weak, the deprotonated molecular ion [M-H](-)m/z 471.3 was employed as both the precursor ion and the product ion. But the collision energy was still used for the MRM, in order to eliminate the influences induced by the interference

  4. High-sensitive LC-MS/MS method for the simultaneous determination of mirodenafil and its major metabolite, SK-3541, in human plasma: application to microdose clinical trials of mirodenafil.

    Science.gov (United States)

    Cho, Doo-Yeoun; Bae, Soo Hyeon; Shon, Ji-Hong; Bae, Soo Kyung

    2013-03-01

    A high-sensitivity LC/MS/MS method was developed and validated for the simultaneous determination of mirodenafil and its major metabolite, SK-3541, in human plasma. Mirodenafil, SK-3541, and udenafil as an internal standard were extracted from plasma samples with methyl tert-butyl ether. Chromatographic separation was performed on a Luna phenyl-hexyl column (100 × 2.0 mm) with an isocratic mobile phase consisting of 5 mM ammonium formate and ACN (23:77, v/v) at a flow rate of 0.35 mL/min. Detection and quantification were performed using a mass spectrometer in selected reaction monitoring mode with positive ESI at m/z 532.3 → 296.1 for mirodenafil, m/z 488.1 → 296.1 for SK-3541, and m/z 517.3 → 283.2 for udenafil. The calibration curves were linear over a concentration range of 2-500 pg/mL using 0.5 mL plasma for the microdose of mirodenafil (100 μg). Analytical method validation of the clinical dose (100 mg), with a calibration curve range of 2-500 ng/mL using 0.025-mL plasma, was also conducted. The other LC-MS/MS conditions were similar to those used for the microdosing. Each method was applied successfully to pharmacokinetic studies after a microdose or clinical dose of mirodenafil to six healthy Korean male volunteers. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Major and minor arsenic compounds accounting for the total urinary excretion of arsenic following intake of blue mussels (Mytilus edulis): A controlled human study

    DEFF Research Database (Denmark)

    Molin, M.; Ydersbond, T.A.; Ulven, S.M.

    2012-01-01

    Blue mussels (Mytilus edulis) accumulate and biotransform arsenic (As) to a larger variety of arsenicals than most seafood. Eight volunteers ingested a test meal consisting of 150g blue mussel (680μg As), followed by 72h with an identical, low As controlled diet and full urine sampling. We provide...... a complete speciation, with individual patterns, of urinary As excretion. Total As (tAs) urinary excretion was 328±47μg, whereof arsenobetaine (AB) and dimethylarsinate (DMA) accounted for 66% and 21%, respectively. Fifteen minor urinary arsenicals were quantified with inductively coupled plasma mass...... spectrometry (ICPMS) coupled to reverse-phase, anion and cation-exchange high performance liquid chromatography (HPLC). Thio-arsenicals and non-thio minor arsenicals (including inorganic As (iAs) and methylarsonate (MA)) contributed 10% and 7% of the total sum of species excretion, respectively, but there were...

  6. Arsenic, Anaerobes, and Astrobiology

    Science.gov (United States)

    Stolz, J. F.; Oremland, R. S.; Switzer Blum, J.; Hoeft, S. E.; Baesman, S. M.; Bennett, S.; Miller, L. G.; Kulp, T. R.; Saltikov, C.

    2013-12-01

    Arsenic is an element best known for its highly poisonous nature, so it is not something one would associate with being a well-spring for life. Yet discoveries made over the past two decades have delineated that not only are some microbes resistant to arsenic, but that this element's primary redox states can be exploited to conserve energy and support prokaryotic growth ('arsenotrophy') in the absence of oxygen. Hence, arsenite [As(III)] can serve as an electron donor for chemo- or photo-autotrophy while arsenate [As(V)] will serve as an electron acceptor for chemo-heterotrophs and chemo-autotrophs. The phylogenetic diversity of these microbes is broad, encompassing many individual species from diverse taxonomic groups in the Domain Bacteria, with fewer representatives in the Domain Archaea. Speculation with regard to the evolutionary origins of the key functional genes in anaerobic arsenic transformations (arrA and arxA) and aerobic oxidation (aioB) has led to a disputation as to which gene and function is the most ancient and whether arsenic metabolism extended back into the Archaean. Regardless of its origin, robust arsenic metabolism has been documented in extreme environments that are rich in their arsenic content, such as hot springs and especially hypersaline soda lakes associated with volcanic regions. Searles Lake, CA is an extreme, salt-saturated end member where vigorous arsenic metabolism occurs, but there is no detectable sulfate-reduction or methanogenesis. The latter processes are too weak bio-energetically to survive as compared with arsenotrophy, and are also highly sensitive to the abundance of borate ions present in these locales. These observations have implications with respect to the search for microbial life elsewhere in the Solar System where volcanic-like processes have been operative. Hence, because of the likelihood of encountering dense brines in the regolith of Mars (formed by evapo-concentration) or beneath the ice layers of Europa

  7. Ameliorative effects of selenium on arsenic-induced cytotoxicity in PC12 cells via modulating autophagy/apoptosis.

    Science.gov (United States)

    Rahman, Md Mostafizur; Uson-Lopez, Rachael A; Sikder, Md Tajuddin; Tan, Gongxun; Hosokawa, Toshiyuki; Saito, Takeshi; Kurasaki, Masaaki

    2018-04-01

    Arsenic is well known toxicant responsible for human diseases including cancers. On the other hand, selenium is an essential trace element with significant chemopreventive effects, anticancer potentials and antioxidant properties. Although previous studies have reported antagonism/synergism between arsenic and selenium in biological systems, the biomolecular mechanism/s is still inconclusive. Therefore, to elucidate the molecular phenomena in cellular level, we hypothesized that co-exposure of selenium with arsenic may have suppressive effects on arsenic-induced cytotoxicity. We found that selenium in co-exposure with arsenic increases cell viability, and suppresses oxidative stress induced by arsenic in PC12 cells. Consequently, DNA fragmentation due to arsenic exposure was also reduced by arsenic and selenium co-exposure. Furthermore, western blot analyses revealed that simultaneous exposure of both metals significantly inhibited autophagy which further suppressed apoptosis through positively regulation of key proteins; p-mTOR, p-Akt, p-Foxo1A, p62, and expression of ubiquitin, Bax, Bcl2, NFкB, and caspases 3 and 9, although those are negatively regulated by arsenic. In addition, reverse transcriptase PCR analysis confirmed the involvement of caspase cascade in cell death process induced by arsenic and subsequent inhibition by co-exposure of selenium with arsenic. The cellular accumulation study of arsenic in presence/absence of selenium via inductively coupled plasma mass spectrometry confirmed that selenium effectively retarded the uptake of arsenic in PC12 cells. Finally, these findings imply that selenium is capable to modulate arsenic-induced intrinsic apoptosis pathway via enhancement of mTOR/Akt autophagy signaling pathway through employing antioxidant potentials and through inhibiting the cellular accumulation of arsenic in PC12 cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Arsenic deposition in tissues of the European hare (Lepus europaeus

    Directory of Open Access Journals (Sweden)

    Karel Bukovjan

    2016-01-01

    Full Text Available The work deals with arsenic deposition in individual biological matrices of the European hare (Lepus europaeus Pall.. The aim of this work was to evaluate the arsenic deposition in biological matrices of adult hares distributed by sex, and to highlight the need for monitoring this element in the natural environment. Determination of arsenic concentration was carried out on 11 biomarkers in 105 adult hares from variously loaded areas of the Czech Republic. Individual matrices include the liver, kidneys, brain, adipose tissue, reproductive organs, bone, fur, faeces, lungs, skeletal muscle and the heart. Inductively coupled plasma mass spectrometry was employed as a method to detect arsenic concentrations in the tissues. Arsenic deposition in the monitored biological matrices of adult animals showed no significant differences between sexes. The ratio of arsenic concentration in the skeletal muscle as compared with concentration in other tissues was 1:2.96 in the liver, followed by 1:4.35 in kidneys, 1:1.07 in the heart, 1:2.73 in lungs, 1:3.12 in ovaries, 1:3.30 in testicles, 1:5.90 in bones, 1:114.68 in fur, and 1:60.05 in faeces. Deposition of this element in matrices has a similar character and only differs in concentrations.

  9. [Arsenic - Poison or medicine?].

    Science.gov (United States)

    Kulik-Kupka, Karolina; Koszowska, Aneta; Brończyk-Puzoń, Anna; Nowak, Justyna; Gwizdek, Katarzyna; Zubelewicz-Szkodzińska, Barbara

    2016-01-01

    Arsenic (As) is commonly known as a poison. Only a few people know that As has also been widely used in medicine. In the past years As and its compounds were used as a medicine for the treatment of such diseases as diabetes, psoriasis, syphilis, skin ulcers and joint diseases. Nowadays As is also used especially in the treatment of patients with acute promyelocytic leukemia. The International Agency for Research on Cancer (IARC) has recognized arsenic as an element with carcinogenic effect evidenced by epidemiological studies, but as previously mentioned it is also used in the treatment of neoplastic diseases. This underlines the specificity of the arsenic effects. Arsenic occurs widely in the natural environment, for example, it is present in soil and water, which contributes to its migration to food products. Long exposure to this element may lead to liver damages and also to changes in myocardium. Bearing in mind that such serious health problems can occur, monitoring of the As presence in the environmental media plays a very important role. In addition, the occupational risk of As exposure in the workplace should be identified and checked. Also the standards for As presence in food should be established. This paper presents a review of the 2015 publications based on the Medical database like PubMed and Polish Medical Bibliography. It includes the most important information about arsenic in both forms, poison and medicine. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  10. Development and validation of an improved LC-MS/MS method for the quantification of desloratadine and its metabolite in human plasma using deutrated desloratadine as internal standard

    Directory of Open Access Journals (Sweden)

    M Saquib Hasnain

    2013-01-01

    Full Text Available Purpose: For the determination of desloratadine (DES and 3-OH desloratadine (3-OHD in human plasma using deutrated desloratadine (DESD5 as internal standard (IS, a novel stability indicating liquid chromatography-tandem mass spectrometric method was developed and validated to support the clinical advancement. Materials and Methods: The solid-phase extraction method used for sample preparation and calibration range was 100-11,000 pg/ml, for which a quadratic regression (1/x 2 was best fitted. The blank plasma was screened and observed free from any endogenous interference. Results: The accuracy (% nominal at low limit of quantification LLOQ level for DES and 3-OHD was 100.4% and 99.9% whereas precision (%CV was 4.6 and 5.1%. They (DES and 3-OHD were stable in human plasma after five freeze-thaw cycles, at room temperature for 23.8 hour, bench top stability for 6.4 hour. Conclusion: This method fulfills all the regulatory requirements for selectivity, sensitivity, precision, accuracy, stability, goodness of fit, and ruggedness of the method for the determination of DES and 3-OHD in human plasma.

  11. Distribution of soil arsenic species, lead and arsenic bound to humic acid molar mass fractions in a contaminated apple orchard

    International Nuclear Information System (INIS)

    Newton, Kimberly; Amarasiriwardena, Dulasiri; Xing, Baoshan

    2006-01-01

    Excessive application of lead arsenate pesticides in apple orchards during the early 1900s has led to the accumulation of lead and arsenic in these soils. Lead and arsenic bound to soil humic acids (HA) and soil arsenic species in a western Massachusetts apple orchard was investigated. The metal-humate binding profiles of Pb and As were analyzed with size exclusion chromatography-inductively coupled plasma mass spectrometry (SEC-ICP-MS). It was observed that both Pb and As bind 'tightly' to soil HA molar mass fractions. The surface soils of the apple orchard contained a ratio of about 14:1 of water soluble As (V) to As (III), while mono-methyl (MMA) and di-methyl arsenic (DMA) were not detectable. The control soil contained comparatively very low levels of As (III) and As (V). The analysis of soil core samples demonstrated that As (III) and As (V) species are confined to the top 20 cm of the soil. - The distribution of arsenic species [i.e., As (III), As (V), and methylated arsenic species (DMA, MMA)] on the soil surface and in a depth profile as well as those associated with humic acids is discussed

  12. Is arsenobetaine the major arsenic compound in the liver of birds marine mammals, and sea turtles?

    Science.gov (United States)

    Kubota, R.; Kunito, T.; Tanabe, S.

    2003-05-01

    Concentrations of total arsenic and individual arsenic compounds were determined in the livers of birds, marine mammals, and sea turtles by using hydride generation-atomic absorption spectrometry (HG-AAS) and high performance liquid chromatography/inductively coupled plasma-mass spectrometry (HPLC/ICP-MS). Marine mammals feeding on cephalopods and crustaceans accumulated higher arsenic concentrations than the species feeding on fishes. No significant age and gender differences in arsenic concentrations were observed for most of the species of marine mammals. Elevated total arsenic concentrations were found in livers of black-footed albatross and loggerhead turtles and these values were comparable to those of lower trophic marine animals. Arsenobetaine was the major arsenical in the livers of most of the species examined. Particularly, in seabirds, mean proportions of arsenobetaine was more than90% of total extractable arsenic In contast, arsenobetaine was a minor constituent in dugong. The compositions of arsenic compounds were different among the species examined. These results might be due to the differences in the metabolic capacity among species and/or the different compositions of arsenic compounds in their preys.

  13. A Potential Synergy between Incomplete Arsenic Methylation Capacity and Demographic Characteristics on the Risk of Hypertension: Findings from a Cross-Sectional Study in an Arsenic-Endemic Area of Inner Mongolia, China

    Directory of Open Access Journals (Sweden)

    Yongfang Li

    2015-03-01

    Full Text Available Inefficient arsenic methylation capacity has been associated with various health hazards induced by arsenic. In this study, we aimed to explore the interaction effect of lower arsenic methylation capacity with demographic characteristics on hypertension risk. A total of 512 adult participants (126 hypertension subjects and 386 non-hypertension subjects residing in an arsenic-endemic area in Inner Mongolia, China were included. Urinary levels of inorganic arsenic (iAs, monomethylarsonic acid (MMA, and dimethylarsinic acid (DMA were measured for all subjects. The percentage of urinary arsenic metabolites (iAs%, MMA%, and DMA%, primary methylation index (PMI and secondary methylation index (SMI were calculated to assess arsenic methylation capacity of individuals. Results showed that participants carrying a lower methylation capacity, which is characterized by lower DMA% and SMI, have a higher risk of hypertension compared to their corresponding references after adjusting for multiple confounders. A potential synergy between poor arsenic methylation capacity (higher MMA%, lower DMA% and SMI and older age or higher BMI were detected. The joint effects of higher MMA% and lower SMI with cigarette smoking also suggest some evidence of synergism. The findings of present study indicated that inefficient arsenic methylation capacity was associated with hypertension and the effect might be enhanced by certain demographic factors.

  14. Simultaneous quantification of tafetinib (SIM010603), a novel potent inhibitor of receptor tyrosine kinase, and its major metabolite in dog plasma by HPLC-ESI/MS/MS and its application to a pharmacokinetic study.

    Science.gov (United States)

    Shao, Feng; Zhu, Tian; Tang, Feng; Liu, Xin

    2013-01-01

    This study presents a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI/MS/MS) technique for the simultaneous determination of tafetinib (SIM010603) and its main metabolite (M1) in dog plasma by using Prazosin hydrochloric acid as the internal standard (IS). Both compounds were extracted from dog plasma with ethyl acetate and were separated by HPLC on a reversed phase C₁₈ column with a mobile phase of 10 mM ammonium acetate buffer containing 0.1% formic acid-acetonitrile (40:60, v/v) at a flow rate of 0.2 mL/min. For quantification, the triple-quadruple MS was used in selected reaction monitoring (SRM) mode. The monitored transitions were m/z 425.3 → 309.2 for tafetinib, m/z 397.2 → 309.2 for M1 and m/z 384.2 → 247.1 for IS. The developed method had a short run time of 4 min and good linearity was observed over a wide range of 1-1000 ng/mL for the two compounds. The method was successfully applied in the pharmacokinetic study of tafetinib and M1 in dog. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Environmental source of arsenic exposure.

    Science.gov (United States)

    Chung, Jin-Yong; Yu, Seung-Do; Hong, Young-Seoub

    2014-09-01

    Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a recent World Health Organization report, arsenic from contaminated water can be quickly and easily absorbed and depending on its metabolic form, may adversely affect human health. Recently, the US Food and Drug Administration regulations for metals found in cosmetics to protect consumers against contaminations deemed deleterious to health; some cosmetics were found to contain a variety of chemicals including heavy metals, which are sometimes used as preservatives. Moreover, developing countries tend to have a growing number of industrial factories that unfortunately, harm the environment, especially in cities where industrial and vehicle emissions, as well as household activities, cause serious air pollution. Air is also an important source of arsenic exposure in areas with industrial activity. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. Taken together, various potential pathways of arsenic exposure seem to affect humans adversely, and future efforts to reduce arsenic exposure caused by environmental factors should be made.

  16. Environmental Source of Arsenic Exposure

    Directory of Open Access Journals (Sweden)

    Jin-Yong Chung

    2014-09-01

    Full Text Available Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a recent World Health Organization report, arsenic from contaminated water can be quickly and easily absorbed and depending on its metabolic form, may adversely affect human health. Recently, the US Food and Drug Administration regulations for metals found in cosmetics to protect consumers against contaminations deemed deleterious to health; some cosmetics were found to contain a variety of chemicals including heavy metals, which are sometimes used as preservatives. Moreover, developing countries tend to have a growing number of industrial factories that unfortunately, harm the environment, especially in cities where industrial and vehicle emissions, as well as household activities, cause serious air pollution. Air is also an important source of arsenic exposure in areas with industrial activity. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. Taken together, various potential pathways of arsenic exposure seem to affect humans adversely, and future efforts to reduce arsenic exposure caused by environmental factors should be made.

  17. ARSENIC SPECIATION ANALYSIS IN HUMAN SALIVA

    Science.gov (United States)

    Background: Determination of arsenic species in human saliva is potentially useful for biomonitoring of human exposure to arsenic and for studying arsenic metabolism. However, there is no report on the speciation analysis of arsenic in saliva. Methods: Arsenic species in saliva ...

  18. Determination of the pyrethroid insecticide metabolite 3-PBA in plasma and urine samples from farmer and consumer groups in northern Thailand

    Science.gov (United States)

    THIPHOM, SARUNYA; PRAPAMONTOL, TIPPAWAN; CHANTARA, SOMPORN; MANGKLABRUKS, AMPICA; SUPHAVILAI, CHAISUREE; AHN, KI CHANG; GEE, SHIRLEY J.; HAMMOCK, BRUCE D.

    2014-01-01

    In this study, the enzyme-linked immunosorbent assays (ELISA) were modified to detect 3-PBA in plasma (including the adducted form) and urine among a large group of consumers and farmers in an agricultural area. The samples were collected on the same day in the morning from 100 consumers (50 females, 50 males) and 100 farmers (50 females, 50 males) in the Fang district, Chiang Mai province, northern Thailand. The ELISA was very sensitive having an IC50 value of 26.7 and 15.3 ng/mL, a limit of quantitation of 5 and 2.5 ng/mL and a limit of detection of 1.08 and 1.94 ng/mL for plasma and urine, respectively. These methods had low (< 5%) intra- and inter-assay coefficients of variation. The extraction technique satisfactorily eliminated the matrix effect from samples before ELISA analysis, yielding good recoveries (85.9–99.4% and 87.3–98.0%, respectively). For the volunteer study, the detection rate for plasma 3-PBA was 24% in consumers and 42% in farmers, but the median and range values were similar (median 5.87 ng/mL, range 5.16–8.44 ng/mL in consumers and 6.27 ng/mL, range 4.29–9.57 ng/mL in farmers). The rate of detection in the urine was similar (76% and 69%, in consumers and in farmers), yet the median concentration was significantly higher in farmers (8.86 μg/g creatinine in consumers vs 16.1 μg/g creatinine in farmers) and the range also much wider in farmers (1.62–80.5 μg/g creatinine in consumers and 0.80–256.2 μg/g creatinine in farmers). There was no correlation between plasma 3-PBA and urinary 3-PBA concentrations in the study presumably because plasma 3-PBA is a measure of cumulative exposures while urinary 3-PBA reflects acute exposures. In addition, metabolism and excretion of pyrethroids varies by individual. Nevertheless, this study demonstrated that these volunteers were exposed to pyrethroids. To our knowledge, this is the first report that compared plasma 3-PBA and urinary 3-PBA in a large group of volunteers. The ELISA method

  19. Chronic subhepatotoxic exposure to arsenic enhances hepatic injury caused by high fat diet in mice

    International Nuclear Information System (INIS)

    Tan, Min; Schmidt, Robin H.; Beier, Juliane I.; Watson, Walter H.; Zhong, Hai; States, J. Christopher; Arteel, Gavin E.

    2011-01-01

    Arsenic is a ubiquitous contaminant in drinking water. Whereas arsenic can be directly hepatotoxic, the concentrations/doses required are generally higher than present in the US water supply. However, physiological/biochemical changes that are alone pathologically inert can enhance the hepatotoxic response to a subsequent stimulus. Such a ‘2-hit’ paradigm is best exemplified in chronic fatty liver diseases. Here, the hypothesis that low arsenic exposure sensitizes liver to hepatotoxicity in a mouse model of non-alcoholic fatty liver disease was tested. Accordingly, male C57Bl/6J mice were exposed to low fat diet (LFD; 13% calories as fat) or high fat diet (HFD; 42% calories as fat) and tap water or arsenic (4.9 ppm as sodium arsenite) for ten weeks. Biochemical and histologic indices of liver damage were determined. High fat diet (± arsenic) significantly increased body weight gain in mice compared with low-fat controls. HFD significantly increased liver to body weight ratios; this variable was unaffected by arsenic exposure. HFD caused steatohepatitis, as indicated by histological assessment and by increases in plasma ALT and AST. Although arsenic exposure had no effect on indices of liver damage in LFD-fed animals, it significantly increased the liver damage caused by HFD. This effect of arsenic correlated with enhanced inflammation and fibrin extracellular matrix (ECM) deposition. These data indicate that subhepatotoxic arsenic exposure enhances the toxicity of HFD. These results also suggest that arsenic exposure might be a risk factor for the development of fatty liver disease in human populations. -- Highlights: ► Characterizes a mouse model of arsenic enhanced NAFLD. ► Arsenic synergistically enhances experimental fatty liver disease at concentrations that cause no overt hepatotoxicity alone. ► This effect is associated with increased inflammation.

  20. Simultaneous determination of cocaine/crack and its metabolites in oral fluid, urine and plasma by liquid chromatography-mass spectrometry and its application in drug users.

    Science.gov (United States)

    Fiorentin, Taís Regina; D'Avila, Felipe Bianchini; Comiran, Eloisa; Zamboni, Amanda; Scherer, Juliana Nichterwitz; Pechansky, Flavio; Borges, Paulo Eduardo Mayorga; Fröehlich, Pedro Eduardo; Limberger, Renata Pereira

    2017-07-01

    A single LC-MS equipment was used to validate three methods for simultaneously analyzing cocaine (COC), benzoylecgonine (BZE), cocaethylene (CE), anhydroecgonine methyl ester (AEME) and anhydroecgonine (AEC) in oral fluid (OF), urine and plasma. The methods were carried out using a Kinetex HILIC column for polar compounds at 30°C. Mobile phase with isocratic condition of acetonitrile: 13mM ammonium acetate pH 6.0: methanol (55:35:10 v/v/v) at 0.8mL/min flow rate was used. After buffer dilution (OF) and protein precipitation (urine and plasma), calibration curve ranges were 4.25-544ng/mL for oral fluid and 5-320ng/mL for urine and plasma with correlation coefficients (r) between 0.9947 and 0.9992. The lowest concentration of the calibration curves were the lower limit of quantification. No major matrix effect could be noted, demonstrating the efficiency of the cleaning procedure. The methods were fully validated and proved to be suitable for analysis of 124 cocaine and/or crack cocaine users. Among the subjects, 56.5% reported daily use of cocaine in the previous three months. Results show a high prevalence of the analytes, with BZE as the most prevalent (94 cases), followed by COC (93 cases), AEC (70 cases), CE (33 cases) and AEME (13 cases). In addition, the concentration of BZE in urine was higher compared to OF and plasma found in the real samples, showing the facility of accumulation in chronic users in matrices with a large detection window. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. A novel HPLC-MS/MS method for the simultaneous determination of astemizole and its major metabolite in dog or monkey plasma and application to pharmacokinetics.

    Science.gov (United States)

    Back, Hyun-moon; Lee, Jong-Hwa; Chae, Jung-woo; Song, Byungjeong; Seo, Joung-Wook; Yun, Hwi-yeol; Kwon, Kwang-il

    2015-10-10

    Astemizole (AST), a second-generation antihistamine, is metabolized to desmethyl astemizole (DEA), and although it has been removed from the market for inducing QT interval prolongation, it has reemerged as a potential anticancer and antimalarial agent. This report describes a novel high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for simultaneously determining the concentrations of AST and DEA in beagle dog and cynomolgus monkey plasma with simple preparation method and short retention time. Prior to HPLC analyses, the plasma samples were extracted with simple liquid-liquid extraction method. The isocratic mobile phase was 0.025% trifluoroacetic acid (TFA dissolved in acetonitrile) and 20 mM ammonium acetate (94:6) at a flow rate of 0.25 mL/min and diphenhydramine used as internal standard. In MS/MS analyses, precursor ions of the analytes were optimized as protonated molecular ions: [M+H](+). The lower limit of quantification of astemizole was 2.5 ng/mL in both species and desmethyl astemizole were 7.5 ng/mL and 10 ng/mL in dog and monkey plasma, respectively. The accuracy, precision, and stability of the method were in accordance with FDA guidelines for the validation of bioanalytical methods. Finally this validated method was successfully applied to a pharmacokinetic study in dogs and monkeys after oral administration of 10 mg/kg AST. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Application of a new procedure for liquid chromatography/mass spectrometry profiling of plasma amino acid-related metabolites and untargeted shotgun proteomics to identify mechanisms and biomarkers of calcific aortic stenosis.

    Science.gov (United States)

    Olkowicz, Mariola; Debski, Janusz; Jablonska, Patrycja; Dadlez, Michal; Smolenski, Ryszard T

    2017-09-29

    Calcific aortic valve stenosis (CAS) increasingly affects our ageing population, but the mechanisms of the disease and its biomarkers are not well established. Recently, plasma amino acid-related metabolite (AA) profiling has attracted attention in studies on pathology and development of biomarkers of cardiovascular diseases, but has not been studied in CAS. To evaluate the potential relationship between CAS and AA metabolome, a new ion-pairing reversed-phase liquid chromatography-tandem mass spectrometry (IP-RPLC-MS/MS) method has been developed and validated for simultaneous determination of 43 AAs in plasma of stenotic patients and age-matched control subjects. Furthermore, untargeted mass spectrometry-based proteomic analysis and confirmatory ELISA assays were performed. The method developed offered high accuracy (intra-assay imprecision averaged 4.4% for all compounds) and sensitivity (LOQ within 0.01-0.5μM). We found that 22 AAs and three AA ratios significantly changed in the CAS group as compared to control. The most pronounced differences were observed in urea cycle-related AAs and branched-chain AA (BCAA)-related AAs. The contents of asymmetric dimethylarginine (ADMA) and its monomethylated derivative (NMMA) were increased by 30-64% with CAS. The arginine/ADMA and Fischer's ratios as well as arginine, homoarginine, ADMA, symmetric dimethylarginine, hydroxyproline, betaine and 3-methylhistidine correlated with cardiac function-related parameters and concomitant systemic factors in the CAS patients. The results of proteomic analysis were consistent with involvement of inflammation, lipid abnormalities, hemostasis and extracellular matrix remodeling in CAS. In conclusion, changes in plasma AA profile and protein pattern that we identified in CAS provide information relevant to pathomechanisms and may deliver new biomarkers of the disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Simultaneous quantification of acetaminophen and five acetaminophen metabolites in human plasma and urine by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry: Method validation and application to a neonatal pharmacokinetic study.

    Science.gov (United States)

    Cook, Sarah F; King, Amber D; van den Anker, John N; Wilkins, Diana G

    2015-12-15

    Drug metabolism plays a key role in acetaminophen (paracetamol)-induced hepatotoxicity, and quantification of acetaminophen metabolites provides critical information about factors influencing susceptibility to acetaminophen-induced hepatotoxicity in clinical and experimental settings. The aims of this study were to develop, validate, and apply high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) methods for simultaneous quantification of acetaminophen, acetaminophen-glucuronide, acetaminophen-sulfate, acetaminophen-glutathione, acetaminophen-cysteine, and acetaminophen-N-acetylcysteine in small volumes of human plasma and urine. In the reported procedures, acetaminophen-d4 and acetaminophen-d3-sulfate were utilized as internal standards (IS). Analytes and IS were recovered from human plasma (10μL) by protein precipitation with acetonitrile. Human urine (10μL) was prepared by fortification with IS followed only by sample dilution. Calibration concentration ranges were tailored to literature values for each analyte in each biological matrix. Prepared samples from plasma and urine were analyzed under the same HPLC-ESI-MS/MS conditions, and chromatographic separation was achieved through use of an Agilent Poroshell 120 EC-C18 column with a 20-min run time per injected sample. The analytes could be accurately and precisely quantified over 2.0-3.5 orders of magnitude. Across both matrices, mean intra- and inter-assay accuracies ranged from 85% to 112%, and intra- and inter-assay imprecision did not exceed 15%. Validation experiments included tests for specificity, recovery and ionization efficiency, inter-individual variability in matrix effects, stock solution stability, and sample stability under a variety of storage and handling conditions (room temperature, freezer, freeze-thaw, and post-preparative). The utility and suitability of the reported procedures were illustrated by analysis of pharmacokinetic samples

  4. Effects of aripiprazole and the Taq1A polymorphism in the dopamine D2 receptor gene on the clinical response and plasma monoamine metabolites level during the acute phase of schizophrenia.

    Science.gov (United States)

    Miura, Itaru; Takeuchi, Satoshi; Katsumi, Akihiko; Mori, Azuma; Kanno, Keiko; Yang, Qiaohui; Mashiko, Hirobumi; Numata, Yoshihiko; Niwa, Shin-Ichi

    2012-02-01

    The Taq1A polymorphism in the dopamine D2 receptor (DRD2) gene could be related to the response to antipsychotics. We examined the effects of the Taq1A polymorphism on the plasma monoamine metabolites during the treatment of schizophrenia with aripiprazole, a DRD2 partial agonist. Thirty Japanese patients with schizophrenia were treated with aripiprazole for 6 weeks. We measured plasma levels of homovanillic acid (pHVA) and 3-methoxy-4hydroxyphenylglycol (pMHPG) before and after treatment. The Taq1A polymorphism was genotyped with polymerase chain reaction. Aripiprazole improved the acute symptoms of schizophrenia and decreased pHVA in responders (P = 0.023) but not in nonresponders (P = 0.28). Although A1 allele carriers showed a tendency to respond to aripiprazole (61.5%) compared to A1 allele noncarriers (29.4%) (P = 0.078), there was not statistically significant difference in the response between the 2 genotype groups. There were significant effect for response (P = 0.013) and genotype × response interaction (P = 0.043) on the change of pHVA. The changes of pHVA differ between responders and nonresponders in A1 allele carriers but not in A1 allele noncarriers. There were no genotype or response effects or genotype × response interaction on the changes of the plasma levels of 3-methoxy-4hydroxyphenylglycol. Our preliminary results suggest that Taq1A polymorphism may be partly associated with changes in pHVA during acute schizophrenia.

  5. Exposure to arsenic in drinking water is associated with increased prevalence of diabetes: a cross-sectional study in the Zimapán and Lagunera regions in Mexico.

    Science.gov (United States)

    Del Razo, Luz M; García-Vargas, Gonzalo G; Valenzuela, Olga L; Castellanos, Erika Hernández; Sánchez-Peña, Luz C; Currier, Jenna M; Drobná, Zuzana; Loomis, Dana; Stýblo, Miroslav

    2011-08-24

    Human exposures to inorganic arsenic (iAs) have been linked to an increased risk of diabetes mellitus. Recent laboratory studies showed that methylated trivalent metabolites of iAs may play key roles in the diabetogenic effects of iAs. Our study examined associations between chronic exposure to iAs in drinking water, metabolism of iAs, and prevalence of diabetes in arsenicosis-endemic areas of Mexico. We used fasting blood glucose (FBG), fasting plasma insulin (FPI), oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), and insulin resistance (HOMA-IR) to characterize diabetic individuals. Arsenic levels in drinking water and urine were determined to estimate exposure to iAs. Urinary concentrations of iAs and its trivalent and pentavalent methylated metabolites were measured to assess iAs metabolism. Associations between diabetes and iAs exposure or urinary metabolites of iAs were estimated by logistic regression with adjustment for age, sex, hypertension and obesity. The prevalence of diabetes was positively associated with iAs in drinking water (OR 1.13 per 10 ppb, p < 0.01) and with the concentration of dimethylarsinite (DMAsIII) in urine (OR 1.24 per inter-quartile range, p = 0.05). Notably, FPI and HOMA-IR were negatively associated with iAs exposure (β -2.08 and -1.64, respectively, p < 0.01), suggesting that the mechanisms of iAs-induced diabetes differ from those underlying type-2 diabetes, which is typically characterized by insulin resistance. Our study confirms a previously reported, but frequently questioned, association between exposure to iAs and diabetes, and is the first to link the risk of diabetes to the production of one of the most toxic metabolites of iAs, DMAsIII.

  6. Exposure to arsenic in drinking water is associated with increased prevalence of diabetes: a cross-sectional study in the Zimapán and Lagunera regions in Mexico

    Science.gov (United States)

    2011-01-01

    Background Human exposures to inorganic arsenic (iAs) have been linked to an increased risk of diabetes mellitus. Recent laboratory studies showed that methylated trivalent metabolites of iAs may play key roles in the diabetogenic effects of iAs. Our study examined associations between chronic exposure to iAs in drinking water, metabolism of iAs, and prevalence of diabetes in arsenicosis-endemic areas of Mexico. Methods We used fasting blood glucose (FBG), fasting plasma insulin (FPI), oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), and insulin resistance (HOMA-IR) to characterize diabetic individuals. Arsenic levels in drinking water and urine were determined to estimate exposure to iAs. Urinary concentrations of iAs and its trivalent and pentavalent methylated metabolites were measured to assess iAs metabolism. Associations between diabetes and iAs exposure or urinary metabolites of iAs were estimated by logistic regression with adjustment for age, sex, hypertension and obesity. Results The prevalence of diabetes was positively associated with iAs in drinking water (OR 1.13 per 10 ppb, p < 0.01) and with the concentration of dimethylarsinite (DMAsIII) in urine (OR 1.24 per inter-quartile range, p = 0.05). Notably, FPI and HOMA-IR were negatively associated with iAs exposure (β -2.08 and -1.64, respectively, p < 0.01), suggesting that the mechanisms of iAs-induced diabetes differ from those underlying type-2 diabetes, which is typically characterized by insulin resistance. Conclusions Our study confirms a previously reported, but frequently questioned, association between exposure to iAs and diabetes, and is the first to link the risk of diabetes to the production of one of the most toxic metabolites of iAs, DMAsIII. PMID:21864395

  7. Determination of LongR3-IGF-I, R3-IGF-I, Des1-3 IGF-I and their metabolites in human plasma samples by means of LC-MS.

    Science.gov (United States)

    Thomas, Andreas; Walpurgis, Katja; Delahaut, Philippe; Fichant, Eric; Schänzer, Wilhelm; Thevis, Mario

    2017-08-01

    According to the regulations of the World Anti-Doping Agency (WADA), growth promoting peptides such as the insulin-like growth factor-I (IGF-I) and its synthetic analogues belong to the class of prohibited compounds. While several assays to quantify endogenous IGF-I have been established, the potential misuse of synthetic analogues such as LongR 3 -IGF-I, R 3 -IGF-I and Des1-3-IGF-I remains a challenge and superior pharmacokinetic properties have been described for these analogues. Within the present study, it was demonstrated that the target peptides can be successfully detected in plasma samples by means of magnetic beads-based immunoaffinity purification and subsequent nanoscale liquid chromatographic separation with high resolution mass spectrometric detection. Noteworthy, the usage of a specific antibody for LongR 3 -IGF-I enables the determination in low ng/mL levels despite the presence of an enormous excess of endogenous human IGF-I. In addition, different metabolism studies (in-vitro and in-vivo) were performed using sophisticated strategies such as incubation with skin tissue microsomes, degradation in biological fluids (for all analogues), and administration to rats (for LongR 3 -IGF-I). Herewith, several C-and N-terminally truncated metabolites were identified and their relevancy was additionally confirmed by in-vivo experiments with rodents. Especially for LongR 3 -IGF-I, a metabolite ((Des1-11)-LongR 3 -IGF-I) was identified that prolonged the detectability in-vivo by a factor of approximately 2. The method was validated for qualitative interpretation considering the parameters specificity, identification capability, recovery (26-60%), limit of detection (0.5ng/mL), imprecision (IGF-I was used as internal standard to control all sample preparation steps. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Arsenic mobilization in sediments

    DEFF Research Database (Denmark)

    Bennett, W. W.; Teasdale, P. R.; Panther, J. G.

    2012-01-01

    We have recently developed Diffusive Gradients in Thin films (DGT) and Diffusive Equilibrium in Thin films (DET) techniques that permit the measurement of high-resolution porewater distributions of As(III), total inorganic arsenic and Fe(II). These novel techniques were utilized to investigate th...

  9. Neuroprotective effect of curcumin in arsenic-induced neurotoxicity in rats.

    Science.gov (United States)

    Yadav, Rajesh S; Shukla, Rajendra K; Sankhwar, Madhu Lata; Patel, Devendra K; Ansari, Reyaz W; Pant, Aditya B; Islam, Fakhrul; Khanna, Vinay K

    2010-09-01

    Our recent studies have shown that arsenic-induced neurobehavioral toxicity is protected by curcumin by modulating oxidative stress and dopaminergic functions in rats. In addition, the neuroprotective effect of curcumin has been investigated on arsenic-induced alterations in biogenic amines, their metabolites and nitric oxide (NO), which play an important role in neurotransmission process. Decrease in the levels of dopamine (DA, 28%), norepinephrine (NE, 54%), epinephrine (EPN, 46%), serotonin (5-HT, 44%), 3,4-dihydroxyphenylacetic acid (DOPAC, 20%) and homovanillic acid (HVA, 31%) in corpus striatum; DA (51%), NE (22%), EPN (47%), 5-HT (25%), DOPAC (34%) and HVA (41%) in frontal cortex and DA (35%), NE (35%), EPN (29%), 5-HT (54%), DOPAC (37%) and HVA (46%) in hippocampus, observed in arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) treated rats exhibited a trend of recovery in rats simultaneously treated with arsenic and curcumin (100 mg/kg body weight, p.o., 28 days). Increased levels of NO in corpus striatum (2.4-fold), frontal cortex (6.1-fold) and hippocampus (6.2-fold) in arsenic-treated rats were found decreased in rats simultaneously treated with arsenic and curcumin. It is evident that curcumin modulates levels of brain biogenic amines and NO in arsenic-exposed rats and these results further strengthen its neuroprotective efficacy. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Napoleon Bonaparte's exposure to arsenic during 1816.

    Science.gov (United States)

    Leslie, A C; Smith, H

    1978-12-11

    Analysis of hair from Napoleon showed that he was exposed to considerable amounts of arsenic during 1816. The distribution pattern of the arsenic in the hair is similar to that found after the daily ingestion of excessive amounts of arsenic.

  11. Individual differences in arsenic metabolism and lung cancer in a case-control study in Cordoba, Argentina

    International Nuclear Information System (INIS)

    Steinmaus, Craig; Yuan Yan; Kalman, Dave; Rey, Omar A.; Skibola, Christine F.; Dauphine, Dave; Basu, Anamika; Porter, Kristin E.; Hubbard, Alan; Bates, Michael N.; Smith, Martyn T.; Smith, Allan H.

    2010-01-01

    In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although in most people this process is not complete. Previous studies have identified associations between the proportion of urinary MMA (%MMA) and increased risks of several arsenic-related diseases, although none of these reported on lung cancer. In this study, urinary arsenic metabolites were assessed in 45 lung cancer cases and 75 controls from arsenic-exposed areas in Cordoba, Argentina. Folate has also been linked to arsenic-disease susceptibility, thus an exploratory assessment of associations between single nucleotide polymorphisms in folate metabolizing genes, arsenic methylation, and lung cancer was also conducted. In analyses limited to subjects with metabolite concentrations above detection limits, the mean %MMA was higher in cases than in controls (17.5% versus 14.3%, p = 0.01). The lung cancer odds ratio for subjects with %MMA in the upper tertile compared to those in the lowest tertile was 3.09 (95% CI, 1.08-8.81). Although the study size was too small for a definitive conclusion, there was an indication that lung cancer risks might be highest in those with a high %MMA who also carried cystathionine β-synthase (CBS) rs234709 and rs4920037 variant alleles. This study is the first to report an association between individual differences in arsenic metabolism and lung cancer, a leading cause of arsenic-related mortality. These results add to the increasing body of evidence that variation in arsenic metabolism plays an important role in arsenic-disease susceptibility.

  12. Extending lactation in pasture-based dairy cows. II: Effect of genetic strain and diet on plasma hormone and metabolite concentrations.

    Science.gov (United States)

    Kay, J K; Phyn, C V C; Roche, J R; Kolver, E S

    2009-08-01

    Fifty-six genetically divergent New Zealand and North American Holstein-Friesian (HF) cows grazed pasture, and were offered 0, 3, or 6 kg of concentrate DM/cow per day for an extended lactation (605 +/- 8.3 d in milk; mean +/- standard error of the mean). Weekly blood samples collected from individual cows from wk 1 to 10 postpartum (early lactation), and from wk 47 to 63 postpartum (extended lactation) were analyzed for nonesterified fatty acids (NEFA), glucose, insulin, leptin, growth hormone (GH), insulin-like growth factor-I (IGF-I), calcium, and urea. During early lactation, NEFA and GH concentrations were greater and IGF-I concentrations were less, and increased at a slower rate in North American HF. During this 10-wk period, there were no strain effects on plasma glucose, leptin, insulin, or calcium. During the extended lactation period, North American HF had greater NEFA and GH concentrations; there were strain x diet interactions for insulin and leptin, and a tendency for a strain x diet interaction for glucose. These interactions were primarily due to greater plasma insulin, leptin, and glucose concentrations in the New Zealand HF fed 6 kg of concentrate DM/cow per day, a result of excessive body condition in this treatment. In this period, there was no strain effect on plasma IGF-I, calcium, or urea concentration. During early lactation, there was a linear increase in glucose and IGF-I, and a linear decrease in GH and urea with increasing concentrate in the diet. However, plasma calcium, NEFA, insulin, and leptin remained unchanged. During the extended lactation period, there was an effect of feed supplementation on GH and urea, which decreased linearly with increasing concentrate in the diet. There was, however, no supplementation effect on NEFA, calcium, or IGF-I. These data indicate potential strain differences in recoupling of the somatotropic axis, insulin resistance, and energy partitioning, and may help explain the physiology behind the previously

  13. Environmental variation of arsenic levels in human blood determined by neutron activation analysis

    DEFF Research Database (Denmark)

    Heydorn, Kaj

    1970-01-01

    Denmark. Arsenic was determined by neutron activation analysis with radiochemical separation and re-irradiation yield determination. The precision and accuracy of the results have been carefully evaluated in order to permit quantitative tests for the significance of the observed differences. The results......Arsenic levels in blood plasma and red cells from patients with Blackfoot disease, a peripheral arteriosclerosis endemic to a small area in Taiwan, were studied in relation to healthy individuals from the same and other parts of Taiwan and compared with arsenic levels in a control group from...... from Taiwan followed a logarithmic normal distribution, and no difference was found between Blackfoot patients and their healthy family members. However, their overall arsenic levels were higher than the Taiwan average, presumably because of arsenic in their drinking water. Much lower levels were found...

  14. Determination of piperphentonamine and metabolites M1 and M6 in human plasma and urine by LC/MS/MS and its application in a pharmacokinetics study in Chinese healthy volunteers.

    Science.gov (United States)

    Shi, Aixin; Hu, Xin; Li, Kexin; Li, Jian; Han, Liping; Wan, Huayin; Li, Rubing

    2012-11-01

    Piperphentonamine hydrochloride (PPTA) is a new calcium sensitizer. A liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for determination of piperphentonamine and its metabolites M1 and M6 was developed for the first time and applied to a pharmacokinetics study. Protein precipitation was used for pre-treatment of plasma samples, and solid phase extraction method was used for pre-treatment of urine samples. The chromatographic separation was achieved on a C(18) column using gradient elution in this study: A: 1% acetic acid aqueous solution, and B: acetonitrile. The whole analysis lasted for 10.5min and the gradient flow rate was 0.25mL/min constantly. The detection was performed of a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via a positive electrospray ionization source. The results were that the m/z ratios of monitored precursor ions and product ions of PPTA, M1 and M6 were 354.0→191.8, 356.0→148.7 and 358.0→148.7, respectively. From the standard curve, the concentration ranges of both PPTA and M1 in blood and urine samples were 0.1-500ng/mL and 0.1-200ng/mL, respectively; the concentration ranges of M6 in blood sample and urine sample were 0.2-500ng/mL and 0.2-200ng/mL, respectively; and the correlation coefficient of standard curve was r>0.99. A total of 31 healthy Chinese subjects participated in the pharmacokinetic study of single bolus intravenous injection of piperphentonamine hydrochloride. They were divided into three dosage groups and given 0.2, 0.4 and 0.6mg/kg of PPTA. After drug administration, concentrations of PPTA, M1 and M6 in human plasma and urine samples were determined to evaluation the pharmacokinetic characteristics of PPTA and its metabolites M1 and M6. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Development and validation of a high-performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of irinotecan and its main metabolites in human plasma and its application in a clinical pharmacokinetic study.

    Directory of Open Access Journals (Sweden)

    Elena Marangon

    Full Text Available Irinotecan is currently used in several cancer regimens mainly in colorectal cancer (CRC. This drug has a narrow therapeutic range and treatment can lead to side effects, mainly neutropenia and diarrhea, frequently requiring discontinuing or lowering the drug dose. A wide inter-individual variability in irinotecan pharmacokinetic parameters and pharmacodynamics has been reported and associated to patients' genetic background. In particular, a polymorphism in the UGT1A1 gene (UGT1A1*28 has been linked to an impaired detoxification of SN-38 (irinotecan active metabolite to SN-38 glucuronide (SN-38G leading to increased toxicities. Therefore, therapeutic drug monitoring of irinotecan, SN-38 and SN-38G is recommended to personalize therapy. In order to quantify simultaneously irinotecan and its main metabolites in patients' plasma, we developed and validated a new, sensitive and specific HPLC-MS/MS method applicable to all irinotecan dosages used in clinic. This method required a small plasma volume, addition of camptothecin as internal standard and simple protein precipitation. Chromatographic separation was done on a Gemini C18 column (3 μM, 100 mm x 2.0 mm using 0.1% acetic acid/bidistilled water and 0.1% acetic acid/acetonitrile as mobile phases. The mass spectrometer worked with electrospray ionization in positive ion mode and selected reaction monitoring. The standard curves were linear (R2 ≥0.9962 over the concentration ranges (10-10000 ng/mL for irinotecan, 1-500 ng/mL for SN-38 and SN-38G and 1-5000 ng/mL for APC and had good back-calculated accuracy and precision. The intra- and inter-day precision and accuracy, determined on three quality control levels for all the analytes, were always <12.3% and between 89.4% and 113.0%, respectively. Moreover, we evaluated this bioanalytical method by re-analysis of incurred samples as an additional measure of assay reproducibility. This method was successfully applied to a pharmacokinetic study in

  16. Speciation of arsenic in biological samples.

    Science.gov (United States)

    Mandal, Badal Kumar; Ogra, Yasumitsu; Anzai, Kazunori; Suzuki, Kazuo T

    2004-08-01

    Speciation of arsenicals in biological samples is an essential tool to gain insight into its distribution in tissues and its species-specific toxicity to target organs. Biological samples (urine, hair, fingernail) examined in the present study were collected from 41 people of West Bengal, India, who were drinking arsenic (As)-contaminated water, whereas 25 blood and urine samples were collected from a population who stopped drinking As contaminated water 2 years before the blood collection. Speciation of arsenicals in urine, water-methanol extract of freeze-dried red blood cells (RBCs), trichloroacetic acid treated plasma, and water extract of hair and fingernail was carried out by high-performance liquid chromatography (HPLC)-inductively coupled argon plasma mass spectrometry (ICP MS). Urine contained arsenobetaine (AsB, 1.0%), arsenite (iAs(III), 11.3), arsenate (iAs(V), 10.1), monomethylarsonous acid (MMA(III), 6.6), monomethylarsonic acid (MMA(V), 10.5), dimethylarsinous acid (DMA(III), 13.0), and dimethylarsinic acid (DMA(V), 47.5); fingernail contained iAs(III) (62.4%), iAs(V) (20.2), MMA(V) (5.7), DMA(III) (8.9), and DMA(V) (2.8); hair contained iAs(III) (58.9%), iAs(V) (34.8), MMA(V) (2.9), and DMA(V) (3.4); RBCs contained AsB (22.5%) and DMA(V) (77.5); and blood plasma contained AsB (16.7%), iAs(III) (21.1), MMA(V) (27.1), and DMA(V) (35.1). MMA(III), DMA(III), and iAs(V) were not found in any plasma and RBCs samples, but urine contained all of them. Arsenic in urine, fingernails, and hair are positively correlated with water As, suggesting that any of these measurements could be considered as a biomarker to As exposure. Status of urine and exogenous contamination of hair urgently need speciation of As in these samples, but speciation of As in nail is related to its total As (tAs) concentration. Therefore, total As concentrations of nails could be considered as biomarker to As exposure in the endemic areas.

  17. Speciation of arsenic in biological samples

    International Nuclear Information System (INIS)

    Mandal, Badal Kumar; Ogra, Yasumitsu; Anzai, Kazunori; Suzuki, Kazuo T.

    2004-01-01

    Speciation of arsenicals in biological samples is an essential tool to gain insight into its distribution in tissues and its species-specific toxicity to target organs. Biological samples (urine, hair, fingernail) examined in the present study were collected from 41 people of West Bengal, India, who were drinking arsenic (As)-contaminated water, whereas 25 blood and urine samples were collected from a population who stopped drinking As contaminated water 2 years before the blood collection. Speciation of arsenicals in urine, water-methanol extract of freeze-dried red blood cells (RBCs), trichloroacetic acid treated plasma, and water extract of hair and fingernail was carried out by high-performance liquid chromatography (HPLC)-inductively coupled argon plasma mass spectrometry (ICP MS). Urine contained arsenobetaine (AsB, 1.0%), arsenite (iAs III , 11.3), arsenate (iAs V , 10.1), monomethylarsonous acid (MMA III , 6.6), monomethylarsonic acid (MMA V , 10.5), dimethylarsinous acid (DMA III , 13.0), and dimethylarsinic acid (DMA V , 47.5); fingernail contained iAs III (62.4%), iAs V (20.2), MMA V (5.7), DMA III (8.9), and DMA V (2.8); hair contained iAs III (58.9%), iAs V (34.8), MMA V (2.9), and DMA V (3.4); RBCs contained AsB (22.5%) and DMA V (77.5); and blood plasma contained AsB (16.7%), iAs III (21.1), MMA V (27.1), and DMA V (35.1). MMA III , DMA III , and iAs V were not found in any plasma and RBCs samples, but urine contained all of them. Arsenic in urine, fingernails, and hair are positively correlated with water As, suggesting that any of these measurements could be considered as a biomarker to As exposure. Status of urine and exogenous contamination of hair urgently need speciation of As in these samples, but speciation of As in nail is related to its total As (tAs) concentration. Therefore, total As concentrations of nails could be considered as biomarker to As exposure in the endemic areas

  18. Urinary arsenic speciation profiles in mice subchronically exposed to low concentrations of sodium arsenate in drinking water

    Directory of Open Access Journals (Sweden)

    Huijie Wu

    2011-09-01

    Full Text Available Arsenic is a proven human carcinogen. Although the mechanism of its carcinogenicity is still largely unknown, methylation is thought to have an important role to play in arsenic toxicity. In this study, urinary methylation profiles were investigated in female C57BL/6J black mice given drinking water containing 500 μg arsenate (AsV/L, 250 μg AsV/L, or 100 μg AsV/L as sodium arsenate for 2 months. The concentrations of arsenic chosen reflected those in the drinking water often encountered in arsenic-endemic areas. Urine samples were collected from the mice at the end of the exposure period, and the arsenic species were analyzed by high performance liquid chromatography-inductively coupled plasma-mass spectrometry. All detectable arsenic species showed strong linear correlation with the administered dosage. The methylation patterns were similar in all three groups with a slight decrease of dimethylarsinic acid/AsV ratio in the 500-μg/L group, which corresponded to the significantly higher arsenic retention in the tissue. The results indicate that urinary arsenic could be used as a good biomarker for internal dose and potential biological effects. Different doses of arsenic exposure could result in different degrees of methylation, excretion, and tissue retention, and this may contribute to the understanding of arsenic carcinogenicity.

  19. The effects of feeding time on milk production, total-tract digestibility, and daily rhythms of feeding behavior and plasma metabolites and hormones in dairy cows.

    Science.gov (United States)

    Niu, M; Ying, Y; Bartell, P A; Harvatine, K J

    2014-12-01

    The timing of feed intake entrains circadian rhythms regulated by internal clocks in many mammals. The objective of this study was to determine if the timing of feeding entrains daily rhythms in dairy cows. Nine Holstein cows were used in a replicated 3 × 3 Latin square design with 14-d periods. An automated system recorded the timing of feed intake over the last 7 d of each period. Treatments were feeding 1×/d at 0830 h (AM) or 2030 h (PM) and feeding 2×/d in equal amounts at 0830 and 2030 h. All treatments were fed at 110% of daily intake. Cows were milked 2×/d at 0500 and 1700 h. Milk yield and composition were not changed by treatment. Daily intake did not differ, but twice-daily feeding tended to decrease total-tract digestibility of organic matter and neutral detergent fiber (NDF). A treatment by time of day interaction was observed for feeding behavior. The amount of feed consumed in the first 2h after feeding was 70% greater for PM compared with AM feeding. A low rate of intake overnight (2400 to 0500 h; 2.2 ± 0.74% daily intake/h, mean ± SD) and a moderate rate of intake in the afternoon (1200 to 1700 h; 4.8 ± 1.1% daily intake/h) was noted for all treatments, although PM slightly reduced the rate during the afternoon period compared with AM. A treatment by time of day interaction was seen for fecal NDF and indigestible NDF (iNDF) concentration, blood urea nitrogen, plasma glucose and insulin concentrations, body temperature, and lying behavior. Specifically, insulin increased and glucose decreased more after evening feeding than after morning feeding. A cosine function within a 24-h period was used to characterize daily rhythms using a random regression. Rate of feed intake during spontaneous feeding, fecal NDF and iNDF concentration, plasma glucose, insulin, NEFA, body temperature, and lying behavior fit a cosine function within a 24-h period that was modified by treatment. In conclusion, feeding time can reset the daily rhythms of feeding and

  20. Determination and Validation of a Solid-phase Extraction Gas Chromatography-mass Spectrometry for the Quantification of Methadone and Its Principal Metabolite in Human Plasma

    Directory of Open Access Journals (Sweden)

    Fouad Chiadmi

    2015-01-01

    Full Text Available This study aimed to develop a solid-phase extraction gas chromatography-selected ion monitoring-mass spectrometry method for the determination of methadone (MDN and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP in human plasma. The linear response was obtained over the concentration range from 10 to 2000 ng/mL for MDN and EDDP. The absolute recoveries of MDN and EDDP were 95.9%-98.9% and 94.8%-102.4%, with relative standard deviation (RSD ranging from 1.8% to 2.7% and 1.8% to 3.9%, respectively. The intra- and interday precisions were found to be less than 5% for both analytes. The limits of detection of MDN and EDDP were 4 and 5 ng/mL, respectively. The presented method was convenient for therapeutic drug monitoring and pharmacokinetic studies in patients on heroin-assisted MDN therapy.

  1. Arsenic biotransformation by a cyanobacterium Nostoc sp. PCC 7120.

    Science.gov (United States)

    Xue, Xi-Mei; Yan, Yu; Xiong, Chan; Raber, Georg; Francesconi, Kevin; Pan, Ting; Ye, Jun; Zhu, Yong-Guan

    2017-09-01

    Nostoc sp. PCC 7120 (Nostoc), a typical filamentous cyanobacterium ubiquitous in aquatic system, is recognized as a model organism to study prokaryotic cell differentiation and nitrogen fixation. In this study, Nostoc cells incubated with arsenite (As(III)) for two weeks were extracted with dichloromethane/methanol (DCM/MeOH) and the extract was partitioned between water and DCM. Arsenic species in aqueous and DCM layers were determined using high performance liquid chromatography - inductively coupled plasma mass spectrometer/electrospray tandem mass spectrometry (HPLC-ICPMS/ESIMSMS). In addition to inorganic arsenic (iAs), the aqueous layer also contained monomethylarsonate (MAs(V)), dimethylarsinate (DMAs(V)), and the two arsenosugars, namely a glycerol arsenosugar (Oxo-Gly) and a phosphate arsenosugar (Oxo-PO4). Two major arsenosugar phospholipids (AsSugPL982 and AsSugPL984) were detected in DCM fraction. Arsenic in the growth medium was also investigated by HPLC/ICPMS and shown to be present mainly as the inorganic forms As(III) and As(V) accounting for 29%-38% and 29%-57% of the total arsenic respectively. The total arsenic of methylated arsenic, arsenosugars, and arsenosugar phospholipids in Nostoc cells with increasing As(III) exposure were not markedly different, indicating that the transformation to organoarsenic in Nostoc was not dependent on As(III) concentration in the medium. Our results provide new insights into the role of cyanobacteria in the biogeochemical cycling of arsenic. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Arsenic, microbes and contaminated aquifers

    Science.gov (United States)

    Oremland, Ronald S.; Stolz, John F.

    2005-01-01

    The health of tens of millions of people world-wide is at risk from drinking arsenic-contaminated well water. In most cases this arsenic occurs naturally within the sub-surface aquifers, rather than being derived from identifiable point sources of pollution. The mobilization of arsenic into the aqueous phase is the first crucial step in a process that eventually leads to human arsenicosis. Increasing evidence suggests that this is a microbiological phenomenon.

  3. Profiling adrenal 11β-hydroxyandrostenedione metabolites in prostate cancer cells, tissue and plasma: UPC2-MS/MS quantification of 11β-hydroxytestosterone, 11keto-testosterone and 11keto-dihydrotestosterone.

    Science.gov (United States)

    du Toit, Therina; Bloem, Liezl M; Quanson, Jonathan L; Ehlers, Riaan; Serafin, Antonio M; Swart, Amanda C

    2017-02-01

    Adrenal C 19 steroids serve as precursors to active androgens in the prostate. Androstenedione (A4), 11β-hydroxyandrostenedione (11OHA4) and 11β-hydroxytestosterone (11OHT) are metabolised to potent androgen receptor (AR) agonists, dihydrotestosterone (DHT), 11-ketotestosterone (11KT) and 11-ketodihydrotestosterone (11KDHT). The identification of 11OHA4 metabolites, 11KT and 11KDHT, as active androgens has placed a new perspective on adrenal C11-oxy C 19 steroids and their contribution to prostate cancer (PCa). We investigated adrenal androgen metabolism in normal epithelial prostate (PNT2) cells and in androgen-dependent prostate cancer (LNCaP) cells. We also analysed steroid profiles in PCa tissue and plasma, determining the presence of the C 19 steroids and their derivatives using ultra-performance liquid chromatography (UHPLC)- and ultra-performance convergence chromatography tandem mass spectrometry (UPC 2 -MS/MS). In PNT2 cells, sixty percent A4 (60%) was primarily metabolised to 5α-androstanedione (5αDIONE) (40%), testosterone (T) (10%), and androsterone (AST) (10%). T (30%) was primarily metabolised to DHT (10%) while low levels of A4, 5αDIONE and 3αADIOL (≈20%) were detected. Conjugated steroids were not detected and downstream products were present at <0.05μM. Only 20% of 11OHA4 and 11OHT were metabolised with the former yielding 11keto-androstenedione (11KA4), 11KDHT and 11β-hydroxy-5α-androstanedione (11OH-5αDIONE) and the latter yielding 11OHA4, 11KT and 11KDHT with downstream products <0.03μM. In LNCaP cells, A4 (90%) was metabolised to AST-glucuronide via the alternative pathway while T was detected as T-glucuronide with negligible conversion to downstream products. 11OHA4 (80%) and 11OHT (60%) were predominantly metabolised to 11KA4 and 11KT and in both assays more than 50% of 11KT was detected in the unconjugated form. In tissue, we detected C11-oxy C 19 metabolites at significantly higher levels than the C 19 steroids, with

  4. The effects of feeding rations that differ in fiber and fermentable starch within a day on milk production and the daily rhythm of feed intake and plasma hormones and metabolites in dairy cows.

    Science.gov (United States)

    Niu, M; Ying, Y; Bartell, P A; Harvatine, K J

    2017-01-01

    A daily pattern of feed intake, milk synthesis, and plasma metabolites and hormones occurs in dairy cows fed a total mixed ration once or twice a day. The objective of this study was to determine if feeding multiple rations within a day, complementing these rhythms, would improve milk production. Twelve Holstein cows were used in a replicated 3×3 Latin square design with 21-d periods. Cows were housed in tie stalls with feed tubs, and feed weight was recorded every 10 s for observation of feeding behavior. Rations were a low fiber and high fermentable starch ration [LFHS; 27.4% neutral detergent fiber (NDF) and 31.7% starch based on 55.7% corn silage and 14.1% steam-flaked corn], a high fiber and low fermentable starch ration (HFLS; 31.7% NDF and 22.3% starch based on 44% corn silage, 26.3% alfalfa haylage, and no steam-flaked corn), and a total mixed ration that was a 1:3 ratio of LFHS and HFLS (30.7% NDF, 24.5% starch). The control treatment (CON) cows were fed the total mixed ration at 0700h, the high/low treatment (HL) fed HFLS ration at 0700h and LFHS ration at 2200h, and the low/high (LH) treatment fed LFHS ration at 0700h and HFLS ration at 1100h (LFHS and HFLS rations fed at a 1:3 ratio). No effect was found of treatment on daily milk, but LH decreased milk fat concentration and yield compared with HL (0.2 percentage units and 0.24kg, respectively). Daily dry matter and NDF intake and total-tract digestibility did not differ between treatments. The HL treatment reduced intake at the morning-conditioned meal after feeding and reduced intake before the evening feeding. A treatment by time of day interaction was found for fecal NDF and indigestible NDF concentration, blood urea nitrogen (BUN), plasma insulin, and fatty acid concentration, and body temperature. The CON and LH treatments increased the daily amplitude of fecal NDF by 1.0 and 1.1 percentage units compared with HL. Plasma insulin was higher in HL than CON at 0100 and 0400h, but lower at 1300 and

  5. Development and validation of a sensitive UHPLC-MS/MS method for the simultaneous analysis of tramadol, dextromethorphan chlorpheniramine and their major metabolites in human plasma in forensic context: application to pharmacokinetics.

    Science.gov (United States)

    Heneedak, Hala M; Salama, Ismail; Mostafa, Samia; El-Kady, Ehab; El-Sadek, Mohamed

    2015-07-01

    The prerequisites for forensic confirmatory analysis by LC/MS/MS with respect to European Union guidelines are chromatographic separation, a minimum number of two MS/MS transitions to obtain the required identification points and predefined thresholds for the variability of the relative intensities of the MS/MS transitions (MRM transitions) in samples and reference standards. In the present study, a fast, sensitive and robust method to quantify tramadol, chlorpheniramine, dextromethorphan and their major metabolites, O-desmethyltramadol, dsmethyl-chlorpheniramine and dextrophan, respectively, in human plasma using ibuprofen as internal standard (IS) is described. The analytes and the IS were extracted from plasma by a liquid-liquid extraction method using ethyl acetate-diethyl-ether (1:1). Extracted samples were analyzed by ultra-high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS). Chromatographic separation was performed by pumping the mobile phase containing acetonitrile, water and formic acid (89.2:11.7:0.1) for 2.0 min at a flow rate of 0.25 μL/min into a Hypersil-Gold C18 column, 20 × 2.0 mm (1.9 µm) from Thermoscientific, New York, USA. The calibration curve was linear for the six analytes. The intraday precision (RSD) and accuracy (RE) of the method were 3-9.8 and -1.7-4.5%, respectively. The analytical procedure herein described was used to assess the pharmacokinetics of the analytes in 24 healthy volunteers after a single oral dose containing 50 mg of tramadol hydrochloride, 3 mg chlorpheniramine maleate and 15 mg of dextromethorphan hydrobromide. Copyright © 2014 John Wiley & Sons, Ltd.

  6. Determination of 20 trace elements and arsenic species for a realgar-containing traditional Chinese medicine Niuhuang Jiedu tablets by direct inductively coupled plasma-mass spectrometry and high performance liquid chromatography-inductively coupled plasma-mass spectrometry.

    Science.gov (United States)

    Jin, Pengfei; Liang, Xiaoli; Xia, Lufeng; Jahouh, Farid; Wang, Rong; Kuang, Yongmei; Hu, Xin

    2016-01-01

    Niuhuang Jiedu tablet (NHJDT) is a realgar-containing traditional Chinese medicine. A direct inductively coupled plasma-mass spectrometry (ICP-MS) method for the simultaneous determination of 20 trace elements (Mg, K, Ca, Na, Fe, As, Zn, Sr, Ba, Cu, Mn, Ni, Pb, V, Cr, Se, Co, Mo, Cd, Hg) in NHJDT, as well as in water, gastric fluid and intestinal fluid was established. Meanwhile, a high performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) method was developed for the determination of arsenite (As(III)), arsenate (As(V)), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and for the identification of arsenobetaine (AsB) and arsenocholine (AsC) in these extracts. Both methods were fully validated in the respect of linearity, sensitivity, precision, stability and accuracy. The reliability of the ICP-MS method was further evaluated using a certified standard reference material prepared from dried tomato leaves (NIST, SRM 1572a). The analysis showed that some manufacturers formulated lower amount of realgar than required in the Chinese Pharmacopoeia (ChP) in their preparations. In addition, almost same extraction profiles for total As and inorganic As were found in water and in gastrointestinal fluids, while higher extraction rates for other 19 elements were observed in gastrointestinal fluids. Our findings show that the toxicities of Hg, Cu, Cd and Pb in NHJDP are low, while the real As toxicity in NHJDT should be deeply investigated. Copyright © 2015 Elsevier GmbH. All rights reserved.

  7. Toxicity of so-called edible hijiki seaweed (Sargassum fusiforme) containing inorganic arsenic.

    Science.gov (United States)

    Yokoi, Katsuhiko; Konomi, Aki

    2012-07-01

    The UK Food Standards Agency and its counterparts in other countries have warned consumers not to eat hijiki (Sargassum fusiforme; synonym Hizikia fusiformis), a Sargasso seaweed, because it contains large amounts of inorganic arsenic. We investigated dietary exposure of hijiki in weaning male F344/N rats fed an AIN-93G diet supplemented with 3% (w/w) hijiki powder for 7 weeks, compared with those fed only an AIN-93G diet. Body weight, body temperature, blood and tissue arsenic concentrations, plasma biochemistry and hematological parameters were measured. We found that feeding rats a 3% hijiki diet led to a marked accumulation of arsenic in blood and tissues, and evoked a high body temperature and abnormal blood biochemistry including elevated plasma alkaline phosphatase activity and inorganic phosphorus, consistent with arsenic poisoning. These findings should prompt further investigations to identify the health hazards related to consumption of hijiki and related Sargassum species in humans. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Quantitative Determination of Arsenic in Bottled Drinking Water Using Atomic Absorption Spectroscopy

    Directory of Open Access Journals (Sweden)

    Maria Guţu Claudia

    2013-10-01

    Full Text Available Background: Many studies have been performed in the past few years, to determine arsenic speciation in drinking water, food chain and environment, arsenic being a well-recognized carcinogenic and toxic agent mainly in its inorganic species. The instrumental techniques used for arsenic determination, such as hydride generation atomic absorption spectrometry (HGAAS, graphite furnace atomic absorption spectrometry (GFAAS and inductively coupled plasma mass spectrometry (ICP-MS, can provide a great sensitivity only on the total amount. Objective: The aim of this study was to develop a simple and rapid method and to analyze the concentration of total inorganic arsenic in bottled drinking water. Methods: Total arsenic was determined in samples from six different types of commercially available bottled drinking water using atomic absorption spectrometry with electrothermal or hydride generation vaporisation. All drinking water samples were acidified with 0.1M nitric acid to match the acidity of the standards. Results: The method was linear within the studied range (1-5 μg/L, R = 0.9943. The quantification limits for arsenic determination were 0.48 μg/L (HGAAS and 0.03 μg/L (GFAAS. The evaluated arsenic content in drinking water was within the accepted limits provided by law. Conclusions: A simple and sensitive method for the quantification of arsenic in drinking water using atomic absorbtion spectroscopy was described, which can be further used in toxicological studies. As an additional advantage, the system is very fast, efficient and environmental friendly

  9. Polyamine Metabolites Profiling for Characterization of Lung and Liver Cancer Using an LC-Tandem MS Method with Multiple Statistical Data Mining Strategies: Discovering Potential Cancer Biomarkers in Human Plasma and Urine

    Directory of Open Access Journals (Sweden)

    Huarong Xu

    2016-08-01

    Full Text Available Polyamines, one of the most important kind of biomarkers in cancer research, were investigated in order to characterize different cancer types. An integrative approach which combined ultra-high performance liquid chromatography—tandem mass spectrometry detection and multiple statistical data processing strategies including outlier elimination, binary logistic regression analysis and cluster analysis had been developed to discover the characteristic biomarkers of lung and liver cancer. The concentrations of 14 polyamine metabolites in biosamples from lung (n = 50 and liver cancer patients (n = 50 were detected by a validated UHPLC-MS/MS method. Then the concentrations were converted into independent variables to characterize patients of lung and liver cancer by binary logic regression analysis. Significant independent variables were regarded as the potential biomarkers. Cluster analysis was engaged for further verifying. As a result, two values was discovered to identify lung and liver cancer, which were the product of the plasma concentration of putrescine and spermidine; and the ratio of the urine concentration of S-adenosyl-l-methionine and N-acetylspermidine. Results indicated that the established advanced method could be successfully applied to characterize lung and liver cancer, and may also enable a new way of discovering cancer biomarkers and characterizing other types of cancer.

  10. Simultaneous determination of the novel tyrosine kinase inhibitor meditinib and its active metabolite demethylation meditinib in monkey plasma by liquid chromatography-tandem mass spectrometry and its application to pharmacokinetic studies.

    Science.gov (United States)

    Liang, Feng; Kong, Qi; Guo, Yongqi; Wang, Yu; Sun, Dejie; Liu, Shi; Cai, Jinling; Guan, Yongbiao; Ding, Rigao

    2015-08-01

    Meditinib (ME) is a novel tyrosine kinase inhibitor used as an antichronic myeloid leukemia drug. A simple, sensitive and specific LC/MS/MS method was developed and validated for the analysis of ME and its metabolite demethylation meditinib (PI) in monkey plasma using naltrexone as the internal standard. Sample preparation involved protein precipitation with methanol. The analysis was carried out on an Agilent C8 column (3.5 µm, 2.1 × 50 mm). Elution was achieved with a mobile phase gradient varying the proportion of a water solution containing 0.1% formic acid (solvent A) and a 0.1% formic acid in methanol solution (solvent B) at a flow rate of 300 μL/min. The method had a linear calibration curve over the concentration range of 2-1000 ng/mL for ME and 2-1000 ng/mL for PI. The lower limits of quantification of ME and PI were 2 and 2 ng/mL, respectively. The intra- and inter-day precision values were 85%. The assay has been successfully used for pharmacokinetic evaluation of ME and PI using the monkey as an animal model, and those data are reported for the first time. Copyright © 2015 John Wiley & Sons, Ltd.

  11. Isolation and identification of indigenous prokaryotic bacteria from arsenic-contaminated water resources and their impact on arsenic transformation.

    Science.gov (United States)

    Jebelli, Mohammad Ahmadi; Maleki, Afshin; Amoozegar, Mohammad Ali; Kalantar, Enayatollah; Shahmoradi, Behzad; Gharibi, Fardin

    2017-06-01

    Arsenic is a known human carcinogen. Arsenite [As(III), H 3 AsO 3 ] and arsenate [As(V), H 2 AsO 4 - and HAsO 4 2- ] are the two predominant compounds of As found in surface water and groundwater. The aim of this study was to explore a bioremediation strategy for biotransformation of arsenite to arsenate by microorganisms. In this study, Babagorgor Spring, located west of Iran, was selected as the arsenic-contaminated source and its physicochemical characteristics and in situ microbiological composition were analyzed. Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES) analysis indicated that the arsenic level was 614μg/l. Fourteen arsenic tolerant indigenous bacteria were isolated from arsenic-contaminated water using chemically defined medium (CDM), supplemented with 260-3900mg/l arsenite and 1560-21800mg/l arsenate. Among the isolates, a strain As-11 exhibited high ability of arsenic transformation. Biochemical tests were used for bacterial identification and confirmation was conducted by 16S rRNA sequence analysis. Results confirmed that As-11 was related to the genus Pseudomonas. This bacterium showed maximum tolerable concentration to arsenite up to 3250mg/l and arsenate up to 20280mg/l. Under heterotrophic conditions, the bacterium exhibited 48% of As(III) and 78% of As(V) transformation from the medium amended with 130 and 312mg/l of sodium arsenite and sodium arsenate, respectively. Moreover, under chemolithotrophic conditions, bacterium was able to transform 41% of 130mg/l of As(III) from the medium amended with nitrate as the terminal electron acceptor. Pseudomonas strain As-11 was reported as an arsenic transformer, for the first time. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Plasma membrane ATPases

    DEFF Research Database (Denmark)

    Palmgren, Michael Broberg; Bækgaard, Lone; Lopez Marques, Rosa Laura

    2011-01-01

    The plasma membrane separates the cellular contents from the surrounding environment. Nutrients must enter through the plasma membrane in order to reach the cell interior, and toxic metabolites and several ions leave the cell by traveling across the same barrier. Biological pumps in the plasma me...

  13. A Phytoremediation Strategy for Arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Meagher, Richard B.

    2005-06-01

    A Phytoremediation Strategy for Arsenic Progress Report May, 2005 Richard B. Meagher Principal Investigator Arsenic pollution affects the health of several hundred millions of people world wide, and an estimated 10 million Americans have unsafe levels of arsenic in their drinking water. However, few environmentally sound remedies for cleaning up arsenic contaminated soil and water have been proposed. Phytoremediation, the use of plants to extract and sequester environmental pollutants, is one new technology that offers an ecologically sound solution to a devastating problem. We propose that it is less disruptive to the environment to harvest and dispose of several thousand pounds per acre of contaminated aboveground plant material, than to excavate and dispose of 1 to 5 million pounds of contaminated soil per acre (assumes contamination runs 3 ft deep). Our objective is to develop a genetics-based phytoremediation strategy for arsenic removal that can be used in any plant species. This strategy requires the enhanced expression of several transgenes from diverse sources. Our working hypothesis is that organ-specific expression of several genes controlling the transport, electrochemical state, and binding of arsenic will result in the efficient extraction and hyperaccumulation of arsenic into aboveground plant tissues. This hypothesis is supported by theoretical arguments and strong preliminary data. We proposed six Specific Aims focused on testing and developing this arsenic phytoremediation strategy. During the first 18 months of the grant we made significant progress on five Specific Aims and began work on the sixth as summarized below. Specific Aim 1: Enhance plant arsenic resistance and greatly expand sinks for arsenite by expressing elevated levels of thiol-rich, arsenic-binding peptides. Hyperaccumulation of arsenic depends upon making plants that are both highly tolerant to arsenic and that have the capacity to store large amounts of arsenic aboveground

  14. Maternal Arsenic Exposure, Arsenic Methylation Efficiency, and Birth Outcomes in the Biomarkers of Exposure to ARsenic (BEAR) Pregnancy Cohort in Mexico

    Science.gov (United States)

    Laine, Jessica E.; Bailey, Kathryn A.; Rubio-Andrade, Marisela; Olshan, Andrew F.; Smeester, Lisa; Drobná, Zuzana; Herring, Amy H.; Stýblo, Miroslav; García-Vargas, Gonzalo G.

    2014-01-01

    Background: Exposure to inorganic arsenic (iAs) from drinking water is a global public health problem, yet much remains unknown about the extent of exposure in susceptible populations. Objectives: We aimed to establish the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort in Gómez Palacio, Mexico, to better understand the effects of iAs exposure on pregnant women and their children. Methods: Two hundred pregnant women were recruited for this study. Concentrations of iAs in drinking water (DW-iAs) and maternal urinary concentrations of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) were determined. Birth outcomes were analyzed for their relationship to DW-iAs and to the concentrations and proportions of maternal urinary arsenicals. Results: DW-iAs for the study subjects ranged from iAs that exceeded the World Health Organization’s recommended guideline of 10 μg As/L. DW-iAs was significantly associated with the sum of the urinary arsenicals (U-tAs). Maternal urinary concentrations of MMAs were negatively associated with newborn birth weight and gestational age. Maternal urinary concentrations of iAs were associated with lower mean gestational age and newborn length. Conclusions: Biomonitoring results demonstrate that pregnant women in Gómez Palacio are exposed to potentially harmful levels of DW-iAs. The data support a relationship between iAs metabolism in pregnant women and adverse birth outcomes. The results underscore the risks associated with iAs exposure in vulnerable populations. Citation: Laine JE, Bailey KA, Rubio-Andrade M, Olshan AF, Smeester L, Drobná Z, Herring AH, Stýblo M, García-Vargas GG, Fry RC. 2015. Maternal arsenic exposure, arsenic methylation efficiency, and birth outcomes in the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Mexico. Environ Health Perspect 123:186–192; http://dx.doi.org/10.1289/ehp.1307476 PMID:25325819

  15. The potential biological mechanisms of arsenic-induced diabetes mellitus

    International Nuclear Information System (INIS)

    Tseng, C.-H.

    2004-01-01

    Although epidemiologic studies carried out in Taiwan, Bangladesh, and Sweden have demonstrated a diabetogenic effect of arsenic, the mechanisms remain unclear and require further investigation. This paper reviewed the potential biological mechanisms of arsenic-induced diabetes mellitus based on the current knowledge of the biochemical properties of arsenic. Arsenate can substitute phosphate in the formation of adenosine triphosphate (ATP) and other phosphate intermediates involved in glucose metabolism, which could theoretically slow down the normal metabolism of glucose, interrupt the production of energy, and interfere with the ATP-dependent insulin secretion. However, the concentration of arsenate required for such reaction is high and not physiologically relevant, and these effects may only happen in acute intoxication and may not be effective in subjects chronically exposed to low-dose arsenic. On the other hand, arsenite has high affinity for sulfhydryl groups and thus can form covalent bonds with the disulfide bridges in the molecules of insulin, insulin receptors, glucose transporters (GLUTs), and enzymes involved in glucose metabolism (e.g., pyruvate dehydrogenase and α-ketoglutarate dehydrogenase). As a result, the normal functions of these molecules can be hampered. However