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Sample records for ethyl glucuronide determination

  1. Determination of Ethyl Glucuronide in Hair for Detection of Alcohol Consumption in Patients After Liver Transplantation.

    Science.gov (United States)

    Andresen-Streichert, Hilke; von Rothkirch, Gregor; Vettorazzi, Eik; Mueller, Alexander; Lohse, Ansgar W; Frederking, Dorothea; Seegers, Barbara; Nashan, Bjoern; Sterneck, Martina

    2015-08-01

    Early detection of alcohol misuse in orthotopic liver transplantation recipients is essential to offer patients support and prevent organ damage. Here, ethyl glucuronide, a metabolite of ethanol found in hair (hEtG), was evaluated for detection of alcohol consumption. In 104 transplant recipients, 31 with underlying alcoholic liver disease (ALD) and 73 with non-ALD, hEtG was determined in addition to the alcohol markers urine EtG, blood ethanol, methanol, and carbohydrate-deficient transferrin. Results were compared with patients' self-reports in a questionnaire and with physicians' assessments. By physicians' assessments, 22% of the patients were suspected of consuming alcohol regularly, although only 6% of the patients acknowledged consumption of a moderate or high amount of alcohol. By testing all markers except for hEtG, alcohol consumption was detected in 7% of the patients. When hEtG testing was added to the assessment, consumption was detected in 17% of the patients. Hair-EtG determination alone revealed chronic alcohol consumption of >10 g/d in 15% of the patients. ALD patients had a positive hEtG result significantly more often than non-ALD patients did (32% versus 8%; P = 0.003). Also, the concentration of hEtG was higher in ALD patients (P = 0.049) and revealed alcohol abuse with consumption of >60 g ethanol per day in 23% of ALD and 3% of non-ALD patients. Patients' self-reports and physicians' assessments had a low sensitivity of 27% and 67%, respectively, for detecting regular alcohol intake as indicated by hEtG. Hair-EtG determination improved the detection of liver transplant patients who used alcohol, and revealed regular alcohol consumption in 32% of ALD and 8% of non-ALD patients.

  2. Determination of ethyl glucuronide in human hair samples: A multivariate analysis of the impact of extraction conditions on quantitative results.

    Science.gov (United States)

    Mueller, Alexander; Jungen, Hilke; Iwersen-Bergmann, Stefanie; Raduenz, Lars; Lezius, Susanne; Andresen-Streichert, Hilke

    2017-02-01

    Ethyl glucuronide (EtG), a minor metabolite of ethanol, is used as a direct alcohol biomarker for the prolonged detection of ethanol consumption. Hair testing for EtG offers retrospective, long-term detection of ethanol exposition for several months and has gained practical importance in forensic and clinical toxicology. Since quantitative results of EtG hair testings are included in interpretations, a rugged quantitation of EtG in hair matrix is important. As generally known, sample preparation is critical in hair testing, and the scope of this study was on extraction of EtG from hair matrix. The influence of extraction solvent, ultrasonication, incubation temperature, incubation time, solvent amount and hair particle size on quantitative results was investigated by a multifactorial experimental design using a validated analytical method and twelve different batches of authentic human hair material. Eight series of extraction experiments in a Plackett-Burman setup were carried out on each hair material with the studied factors at high or low levels. The effect of pulverization was further studied by two additional experimental series. Five independent samplings were performed for each run, resulting in a total number of 600 determinations. Considerable differences in quantitative EtG results were observed, concentrations above and below interpretative cut-offs were obtained from the same hair materials using different extraction conditions. Statistical analysis revealed extraction solvent and temperature as the most important experimental factors with significant influence on quantitative results. The impact of pulverization depended on other experimental factors and the different hair matrices themselves proved to be important predictors of extraction efficiency. A standardization of extraction procedures should be discussed, since it will probably reduce interlaboratory variabilities and improve the quality and acceptance of hair EtG analysis. Copyright © 2016

  3. Validation of a headspace solid-phase microextraction-GC-MS/MS for the determination of ethyl glucuronide in hair according to forensic guidelines.

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    Agius, Ronald; Nadulski, Thomas; Kahl, Hans-Gerhard; Schräder, Johannes; Dufaux, Bertin; Yegles, Michel; Pragst, Fritz

    2010-03-20

    The analysis of ethyl glucuronide (EtG) in hair is a powerful tool for chronic alcohol abuse control because of the typical wide detection window of the hair matrix and due to the possibility of segmentation, allowing evaluation of alcohol consumption in different periods. Additionally, EtG in hair is often the only diagnostic parameter of choice for alcohol abuse when other clinical parameters such as ALT, AST, gammaGT and CDT (asialotransferrin and disialotransferrin) are in the normal range and EtG in urine negative. In this paper, we describe the development, optimization and validation of a new method based on hair extraction with water, clean-up by solid phase extraction (SPE), derivatization with heptafluorobutyric anhydride and headspace solid-phase microextraction (HS-SPME) in combination with GC-MS/MS according to forensic guidelines. The assay linearity of EtG was confirmed over the range from 2.8 to 1000 pg/mg hair, with a coefficient of determination (r(2)) above 0.999. The LLOQ was 2.8 pg/mg and the LLOD was 0.6 pg/mg. An error profile calculated according to the "Guide to the Expression of Uncertainty in Measurement" (GUM) at 99% confidence intervals for the range 5-750 pg/mg hair did not exceed 10%. This range corresponds to more than 98% of the positive samples analysed. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  4. Influence of Body Mass Index on Hair Ethyl Glucuronide Concentrations.

    Science.gov (United States)

    Crunelle, Cleo L; Neels, Hugo; Maudens, Kristof; De Doncker, Mireille; Cappelle, Delphine; Matthys, Frieda; Dom, Geert; Fransen, Erik; Michielsen, Peter; De Keukeleire, Steven; Covaci, Adrian; Yegles, Michel

    2017-01-01

    Analysis of ethyl glucuronide (EtG) concentrations in hair is increasingly used to estimate the consumption of alcohol of the prior months. Linear correlations between the amount of alcohol consumed and the concentration of EtG in hair have been reported, and several variables that may influence this correlation have been investigated: e.g. cosmetic hair treatments, gender influences or hair color. Here, we investigate the influence of body mass index (BMI) on this correlation. A post hoc analysis on the influence of BMI on the relation between amounts of alcohol consumed and the measured EtG concentrations in hair in 199 participants. Our data show higher EtG concentrations in participants with high BMI (≥25) compared to participants with low BMI (hair EtG concentrations. Ethyl glucuronide concentrations in hair (hEtG) can be used to estimate the consumption of alcohol of the prior months. Body mass index (BMI) influences this relation and BMI should be taken into account when interpreting hEtG concentrations in participants with high BMI (≥25) compared to participants with low BMI (<25). © The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  5. Ethyl glucuronide in hair. A sensitive and specific marker of chronic heavy drinking.

    Science.gov (United States)

    Morini, Luca; Politi, Lucia; Polettini, Aldo

    2009-06-01

    This study aims to define a cut-off concentration for ethyl glucuronide in hair to determine if there was a history of heavy drinking. Pavia, Italy. We analysed hair samples from 98 volunteers among teetotallers, social drinkers and heavy drinkers, whose ethanol daily intake (EDI) was estimated by means of a written questionnaire. Ethyl glucuronide hair concentration (HEtG) was measured by liquid chromatography-tandem mass spectrometry (lower limit of quantification: 3 pg/mg) using a fully validated method. The HEtG level providing the best compromise between sensitivity (0.92) and specificity (0.96) at detecting an EDI of 60 g or higher during the last 3 months was 27 pg/mg. None of the factors examined among those known to affect ethanol metabolism and/or the diagnostic power of other markers of ethanol use or hair analyses, including age, gender, body mass index, tobacco smoke, prevalent beverage, hair colour, cosmetic treatments and hygienic habits was found to influence marker performance significantly. However, the slight differences in HEtG performance observed for some factors (e.g. body mass index, smoke and hair treatments) require further studies on larger groups of individuals in order to assess their influence more precisely. Our results confirm further that HEtG is a sensitive and specific marker of chronic heavy drinking.

  6. Voucher-Based Reinforcement for Alcohol Abstinence Using the Ethyl-Glucuronide Alcohol Biomarker

    Science.gov (United States)

    McDonell, Michael G.; Howell, Donelle N,; McPherson, Sterling; Cameron, Jennifer M.; Srebnik, Debra; Roll, John M.; Ries, Richard K.

    2012-01-01

    This study assessed the effects of a contingency management (CM) intervention for alcohol consumption in 10 alcohol-dependent participants. An ABCA design was used. Vouchers were provided contingent on results of ethyl glucuronide (EtG) urine tests (an alcohol biomarker with a 2-day detection period) and alcohol breath tests during the C phase.…

  7. Development and validation of a gas chromatography-negative chemical ionization tandem mass spectrometry method for the determination of ethyl glucuronide in hair and its application to forensic toxicology.

    Science.gov (United States)

    Kharbouche, Hicham; Sporkert, Frank; Troxler, Stéphanie; Augsburger, Marc; Mangin, Patrice; Staub, Christian

    2009-08-01

    Ethyl glucuronide (EtG) is a minor and direct metabolite of ethanol. EtG is incorporated into the growing hair allowing retrospective investigation of chronic alcohol abuse. In this study, we report the development and the validation of a method using gas chromatography-negative chemical ionization tandem mass spectrometry (GC-NCI-MS/MS) for the quantification of EtG in hair. EtG was extracted from about 30 mg of hair by aqueous incubation and purified by solid-phase extraction (SPE) using mixed mode extraction cartridges followed by derivation with perfluoropentanoic anhydride (PFPA). The analysis was performed in the selected reaction monitoring (SRM) mode using the transitions m/z 347-->163 (for the quantification) and m/z 347-->119 (for the identification) for EtG, and m/z 352-->163 for EtG-d(5) used as internal standard. For validation, we prepared quality controls (QC) using hair samples taken post mortem from 2 subjects with a known history of alcoholism. These samples were confirmed by a proficiency test with 7 participating laboratories. The assay linearity of EtG was confirmed over the range from 8.4 to 259.4 pg/mg hair, with a coefficient of determination (r(2)) above 0.999. The limit of detection (LOD) was estimated with 3.0 pg/mg. The lower limit of quantification (LLOQ) of the method was fixed at 8.4 pg/mg. Repeatability and intermediate precision (relative standard deviation, RSD%), tested at 4 QC levels, were less than 13.2%. The analytical method was applied to several hair samples obtained from autopsy cases with a history of alcoholism and/or lesions caused by alcohol. EtG concentrations in hair ranged from 60 to 820 pg/mg hair.

  8. Urine tested positive for ethyl glucuronide and ethyl sulphate after the consumption of "non-alcoholic" beer.

    Science.gov (United States)

    Thierauf, Annette; Gnann, Heike; Wohlfarth, Ariane; Auwärter, Volker; Perdekamp, Markus Grosse; Buttler, Klaus-Juergen; Wurst, Friedrich M; Weinmann, Wolfgang

    2010-10-10

    In abstinence maintenance programs, for reissuing the driving licence and in workplace monitoring programs abstinence from ethanol and its proof are demanded. Various monitoring programs that mainly use ethyl glucuronide (EtG) as alcohol consumption marker have been established. To abstain from ethanol, but not from the taste of alcoholic beverages, in particular non-alcoholic beer has become more and more popular. In Germany, these "alcohol-free" beverages may still have an ethanol content of up to 0.5vol.% without the duty of declaration. Due to severe negative consequences resulting from positive EtG tests, a drinking experiment with 2.5L of non-alcoholic beer per person was performed to address the question of measurable concentrations of the direct metabolites EtG and EtS (ethyl sulphate) in urine and blood. Both alcohol consumption markers - determined by LC-MS/MS - were found in high concentrations: maximum concentrations in urine found in three volunteers were EtG 0.30-0.87mg/L and EtS 0.04-0.07mg/L, i.e., above the often applied cut-off value for the proof of abstinence of 0.1mg EtG/L. In the urine samples of one further volunteer, EtG and EtS concentrations cumulated over-night and reached up to 14.1mg/L EtG and 16.1mg/L EtS in the next morning's urine. Ethanol concentrations in blood and urine samples were negative (determined by HS-GC-FID and by an ADH-based method). Copyright © 2010. Published by Elsevier Ireland Ltd.

  9. Sample preparation method for the combined extraction of ethyl glucuronide and drugs of abuse in hair.

    Science.gov (United States)

    Meier, Ulf; Briellmann, Thomas; Scheurer, Eva; Dussy, Franz

    2017-10-09

    Often in hair analysis, a small hair sample is available while the analysis of a multitude of structurally diverse substances with different concentration ranges is demanded. The analysis of the different substances often requires different sample preparation methods, increasing the amount of required hair sample. When segmental hair analysis is necessary, the amount of hair sample needed is further increased. Therefore, the required sample amount for a full analysis can quickly exceed what is available. To combat this problem, a method for the combined hair sample preparation using a single extraction procedure for analysis of ethyl glucuronide with liquid chromatography-multistage fragmentation mass spectrometry/multiple reaction monitoring (LC-MS3 /MRM) and common drugs of abuse with LC-MRM was developed. The combined sample preparation is achieved by separating ethyl glucuronide from the drugs of abuse into separate extracts by fractionation in the solid-phase extraction step during sample clean-up. A full validation for all substances for the parameters selectivity, linearity, limit of detection, limit of quantification, accuracy, precision, matrix effects, and recovery was successfully completed. The following drugs of abuse were included in the method: Amphetamine; methamphetamine; 3,4-methylenedioxy-N-methylamphetamine (MDMA); 3,4-methylenedioxyamphetamine (MDA); 3,4-methylenedioxy-N-ethylamphetamine (MDE); morphine; 6-monoacetylmorphine; codeine; acetylcodeine; cocaine; benzoylecgonine; norcocaine; cocaethylene; methadone; 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and methylphenidate. In conclusion, as only 1 sample preparation is needed with 1 aliquot of hair, the presented sample preparation allows an optimal analysis of both ethyl glucuronide and of the drugs of abuse, even when the sample amount is a limiting factor. Copyright © 2017 John Wiley & Sons, Ltd.

  10. Analysis and interpretation of specific ethanol metabolites, ethyl sulfate, and ethyl glucuronide in sewage effluent for the quantitative measurement of regional alcohol consumption.

    Science.gov (United States)

    Reid, Malcolm J; Langford, Katherine H; Mørland, Jørg; Thomas, Kevin V

    2011-09-01

    The quantitative measurement of urinary metabolites in sewage streams and the subsequent estimation of consumption rates of the parent compounds have previously been demonstrated for pharmaceuticals and narcotics. Ethyl sulfate and ethyl glucuronide are excreted in urine following the ingestion of alcohol, and are useful biomarkers for the identification of acute alcohol consumption. This study reports a novel ion-exchange-mediated chromatographic method for the quantitative measurement of ethyl sulfate and ethyl glucuronide in sewage effluent, and presents a novel calculation method for the purposes of relating the resulting sewage concentrations with rates of alcohol consumption in the region. A total of 100 sewage samples covering a 25-day period were collected from a treatment plant servicing approximately 500,000 people, and analyzed for levels of ethyl sulfate and ethyl glucuronide. The resulting data were then used to estimate combined alcohol consumption rates for the region, and the results were compared with alcohol related sales statistics for the same region. Ethyl glucuronide was found to be unstable in sewage effluent. Ethyl sulfate was stable and measurable in all samples at concentrations ranging from 16 to 246 nM. The highest concentrations of the alcohol biomarker were observed during weekend periods. Sixty one percent of the total mass of ethyl sulfate in sewage effluent corresponds to alcohol consumption on Friday and Saturday. Sales statistics for alcohol show that consumption in the region is approximately 6,750 kg/d. The quantity of ethyl sulfate passing through the sewage system is consistent with consumption of 4,900 to 7,800 kg/d.   Sewage epidemiology assessments of ethyl sulfate can provide accurate estimates of community alcohol consumption, and detailed examination of the kinetics of this biomarker in sewage streams can also identify time-dependent trends in alcohol consumption patterns. 2011 by the Research Society on Alcoholism.

  11. A specific immunoassay for the determination of morphine and its glucuronides in human blood.

    Science.gov (United States)

    Beike, J; Blaschke, G; Mertz, A; Köhler, H; Brinkmann, B

    1998-01-01

    The development of specific antisera for immunochemical determination of morphine, morphine-3-glucuronide and morphine-6-glucuronide is described. Morphine was N-demethylated to normorphine and N-alkylated to give N-aminopropyl-normorphine as hapten for antisera against morphine. As haptens for antisera against morphine-3-glucuronide and morphine-6-glucuronide, N-aminopropyl-nor-morphine was glucuronidated in position 3 or 6 respectively. Each of these three haptens were coupled to BSA employing the glutaraldehyde method to obtain three different immunogens. Immunisation of rabbits with these conjugates gave anti-morphine, anti-morphine-3-glucuronide and anti-morphine-6-glucuronide antisera, which were tested in a competitive, heterogeneous radioimmunoassay. Tracers for this radioimmunoassay procedure were synthesised by substitution of morphine and morphine-6-glucuronide in position 2 with 125I and indirect iodination of the morphine-3-glucuronide hapten according to the method of Bolton and Hunter. The resulting antisera show very specific reactions with morphine, morphine-3-glucuronide and morphine-6-glucuronide. Cross reactivities of each antiserum with structurally related opiates and opioides are very low. The cross reactivities of the anti-morphine antiserum against morphine-3-glucuronide, morphine-6-glucuronide, codeine, codeine-6-glucuronide or dihydrocodeine were less than 0.3%, the anti-morphine-3-glucuronide antiserum against morphine, morphine-6-glucuronide, codeine, codeine-6-glucuronide or dihydrocodeine less than 0.1% and the anti-morphine-6-glucuronide antiserum against morphine, morphine-3-glucuronide, codeine or dihydrocodeine less than 0.1%, against codeine-6-glucuronide less than 2.3%. The determination of morphine, morphine-3-glucuronide and morphine-6-glucuronide in blood samples (limit of detection= 3, 1, 0.5 ng/g) of nine cases of fatal heroin overdose with this radioimmunoassay method and the comparison with a GC/MS method is described.

  12. Ethyl glucuronide in hair and fingernails as a long-term alcohol biomarker.

    Science.gov (United States)

    Berger, Lisa; Fendrich, Michael; Jones, Joseph; Fuhrmann, Daniel; Plate, Charles; Lewis, Douglas

    2014-03-01

    This study aimed to evaluate the performance of ethyl glucuronide (EtG) in hair and fingernails as a long-term alcohol biomarker. Cross-sectional survey with probability sampling. Midwestern United States. Participants were 606 undergraduate college students between the ages of 18 and 25 years at the time of selection for potential study participation. EtG concentrations in hair and fingernails were measured by liquid chromatography-tandem mass spectrometry at three thresholds [30 picograms (pg) per milligram (mg); 20 pg/mg; and 8 pg/mg]. Any weekly alcohol use, increasing-risk drinking and high-risk drinking on average during the past 12 weeks was assessed by participant interview using the time-line follow-back method. In both hair and fingernails at all three EtG thresholds, sensitivity was greatest for the high-risk drinking group [hair: 0.43, confidence interval (CI)=0.17, 0.69 at 30 pg/mg, 0.71, CI=0.47, 0.95 at 20 pg/mg; 0.93, CI=0.79, 1.00 at 8 pg/mg; fingernails: 1.00, CI=1.00-1.00 at 30, 20 and 8 pg/mg] and specificity was greatest for any alcohol use (hair: 1.00, CI=1.00, 1.00 at 30 and 20 pg/mg; 0.97, CI=0.92-0.99 at 8 pg/mg; fingernails: 1.00, CI=1.00-1.00 at 30, 20 and 8 pg/mg). Areas under the receiver operating characteristic curves were significantly higher for EtG concentration in fingernails than hair for any weekly alcohol use (P = 0.02, DeLong test, two-tailed) and increasing-risk drinking (P = 0.02, DeLong test, two-tailed). Ethyl glucuronide, especially in fingernails, may have potential as a quantitative indicator of alcohol use. © 2013 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

  13. Measurement of ethyl glucuronide in vitreous humor with liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Keten, Alper; Tumer, Ali Riza; Balseven-Odabasi, Aysun

    2009-12-15

    It is important to detect alcohol intake in postmortem investigations. However it can be difficult to interpret the results of alcohol analysis in putrefied corpses. To avoid this difficulty, there have been studies on detection of ethyl glucuronide (EtG), a non-oxidative metabolite of ethyl alcohol. The aim of this study was investigate EtG levels in vitreous humor (VH), a valuable material in postmortem investigations, and to compare VH EtG levels with blood and urine EtG levels. Blood, urine and VH specimens were collected from 110 cases. Twenty-four cases in which ethyl alcohol was detected were included in the study. Although ethanol could not be detected, one case was added after having positive results of EtG levels in urine and VH as if he was claimed that he was an alcoholic and he had taken alcohol when he died but it could not be detected after 6 days of hospitalization. Liquid chromatography-mass spectrometry was used to investigate EtG in blood, urine and VH specimens from 25 cases. VH EtG was in measurable amounts in 19 cases (n: 25). In fact, VH EtG levels ranged from 0.05 to 1.90 mg/L and were below the limit of detection (LOD is 0.03 mg/L) in six cases (n: 25). Blood EtG was in measurable amounts in 21 cases (n: 25). Blood EtG levels ranged from 0.64 to 5.82 mg/L and were below the limit of detection (LOD is 0.083 mg/L) in four cases. EtG was detected in urine in 17 cases (n: 19). Urine EtG levels ranged from 0.25 to 623 mg/L and were below the limit of detection (LOD is 0.12 mg/L) in one case. There was a significant relation between VH EtG levels and blood and urine EtG levels. The results of the study showed that postmortem VH EtG can be measured to reveal alcohol intake.

  14. Hair ethyl glucuronide concentrations in teetotalers: Should we re-evaluate the lower cut-off?

    Science.gov (United States)

    Crunelle, Cleo L; Yegles, Michel; De Doncker, Mireille; Cappelle, Delphine; Covaci, Adrian; van Nuijs, Alexander L N; Neels, Hugo

    2017-05-01

    Ethyl glucuronide in hair (hEtG) can be used to assess the retrospective consumption of alcohol. A lower cut-off of 7pg/mg hair in the 0-3cm proximal scalp hair segment has been used for repeated alcohol consumption in the previous three months. While a concentration below this cut-off is stated not to contradict self reported abstinence, it is often used to assess whether an individual has remained abstinent in the period prior to hair sampling. Here, we address hEtG concentrations in alcohol consuming individuals and critically evaluate this cut-off value. Ten individuals remained abstinent from alcohol for 12 weeks. A lock of hair was cut before the start of the study, and the regrown hairs were cut after twelve weeks of abstinence. Hair EtG concentrations were measured both at baseline and after 12 weeks of abstinence. Study compliance was assessed by urine analysis every 2-3 days by liquid chromatography-tandem mass spectrometry with a lower limit of quantification (LLOQ) of 0.1μg/mL. HEtG concentrations were assessed in the first 3cm hair using gas chromatography-tandem mass spectrometry with an LLOQ of 0.2pg/mg. At the beginning of the study, participants had hEtG concentrations ranging between low, but measurable hEtG concentrations (up to 4.5pg/mg hair), which was in the participant with the highest pre-study alcohol consumption. As only regrown hairs were cut, it is not likely that this was due to residual EtG from the pre-study period. Although the number of specimens was low, this study reports measurable hEtG concentrations following total abstinence, although not exceeding the current 7pg/mg cut-off for hair. A suitable sensitive method (GC-MS/MS) is preferred when assessing alcohol abstinence. We propose that the current cut-off of 7pg/mg should be discussed further, and, in view of the small study sample, evaluated using a larger sample size. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Ethyl glucuronide in human hair after daily consumption of 16 or 32 g of ethanol for 3 months.

    Science.gov (United States)

    Kronstrand, Robert; Brinkhagen, Linda; Nyström, Fredrik H

    2012-02-10

    The overall objectives of the study were to develop a sensitive method for ethyl glucuronide (EtG) determination in hair and then investigate if a low or moderate intake of ethanol could be differentiated from total abstinence. Forty-four subjects were included in the study, 12 males (7 drinkers and 5 abstinent) and 32 females (14 drinkers and 18 abstinent). The study lasted 3 months and the female drinkers consumed one glass (16 g of ethanol) and the males consumed two glasses (32 g of ethanol) of wine (13.5-14%) daily. Hair samples were collected as close as possible above the skin and the proximal 2 cm were analyzed for EtG. Hair was cut into pieces of about 0.5 cm length and washed before incubation overnight in water and then extracted on Clean Screen EtG Carbon columns. The LC/MS/MS system consisted of a Waters ACQUITY UPLC connected to an API 4000 triple quadrupole instrument. Two transitions for EtG and one for the internal standard EtG-D(5) were measured. The method was linear from 60 to 10,000 pg/sample. Imprecision studies were performed at three levels as well as with an authentic sample. Total imprecision was 16% at 200 pg/sample, 8% at 1000 pg/sample, 6% at 8000 pg/sample and 13% at 29 pg/mg in the authentic sample. Of those who drank two glasses of wine every day, four had measurable amounts of EtG in their hair (5-11 pg/mg), and in only one of the females drinking one glass of wine EtG was quantified (3 pg/mg). Among the 23 abstinent subjects two had traces of EtG in the hair. We conclude that persons who ingested 16 or 32 g of ethanol daily for 3 months presented with low concentrations of EtG in hair, well below the proposed threshold for overconsumption set at 30 pg/mg. In addition, none of those who ingested 16 g/day had concentrations over the proposed abstinence threshold of 7 pg/mg. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  16. Detecting alcohol abuse: traditional blood alcohol markers compared to ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) measurement in hair.

    Science.gov (United States)

    Hastedt, Martin; Büchner, Mara; Rothe, Michael; Gapert, René; Herre, Sieglinde; Krumbiegel, Franziska; Tsokos, Michael; Kienast, Thorsten; Heinz, Andreas; Hartwig, Sven

    2013-12-01

    Alcohol abuse is a common problem in society; however, the technical capabilities of evaluating individual alcohol consumption using objective biomarkers are rather limited at present. In recent years research has focused on alcohol markers using hair analysis but data on performance and reliable cut-off values are still lacking. In this study 169 candidates were tested to compare traditional biomarkers, such as carbohydrate-deficient-transferrin (CDT), gamma glutamyl transferase (GGT), aspartate amino transferase, alanine amino transferase and the mean corpuscular volume of the erythrocytes, with alcohol markers detectable in hair such as ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs). This study revealed that EtG, GGT and CDT showed the best results, demonstrating areas under the curve calculated from receiver operating characteristics of 0.941, 0.943 and 0.899 respectively. The lowest false-negative and false-positive rates were obtained by using a combined interpretation system for hair EtG and FAEEs. All markers demonstrated only low to moderate correlations. Optimum cut-off values for differentiation between social and chronic excessive drinking calculated for hair EtG and FAEEs were 28 pg/mg and 0.675 ng/mg, respectively. The critical values published in the "Consensus on Alcohol Markers 2012" by the Society of Hair Testing were confirmed.

  17. An evaluation of washing and extraction techniques in the analysis of ethyl glucuronide and fatty acid ethyl esters from hair samples.

    Science.gov (United States)

    Bossers, L C A M; Paul, R; Berry, A J; Kingston, R; Middendorp, C; Guwy, A J

    2014-03-15

    Ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) are alcohol metabolites measured in hair and are after a decade of research thought to be the best markers in hair to indicate alcoholism and abstinence Forensic Sci. Int. 218 (2012) 2. A great body of work concerning EtG and FAEEs detection in hair has been performed. However, no recent extensive comparison has been made concerning washing and extraction procedures. This work shows that the washing procedure of dichloromethane followed by a methanol rinse of the hair sample removes more than 16% of the FAEEs and 50% of the total EtG that is present in and on the hair. A review of ten washing protocols (where the removal is categorised: high, medium or low) showed that a relatively high percentage of FAEEs was removed and "medium" amount of EtG compared to the other washing protocols. This work shows promising results for the extraction of the FAEEs and the combined extraction of FAEEs and EtG by using 30min of sonication with methanol. More FAEEs were recovered from hair with methanol than with any other extraction solvent including the commonly used dimethyl sulfoxide/heptane mixture. When the sonication time was increased a higher percentage of transesterification of the FAEEs was observed, the extraction was "dirtier" as solids and a colour change was observed whereas the extraction efficiency did not increase. Therefore, washing the hair sample with dichloromethane and methanol followed by an addition of 1ml of methanol and sonication for 30min to extract the FAEEs and EtG from hair is recommended for FAEEs as well as for the combined analysis of EtG and FAEEs. A linear calibration curve (r(2)>0.99) was obtained for all analytes. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. A wearable biochemical sensor for monitoring alcohol consumption lifestyle through Ethyl glucuronide (EtG) detection in human sweat

    Science.gov (United States)

    Panneer Selvam, Anjan; Muthukumar, Sriram; Kamakoti, Vikramshankar; Prasad, Shalini

    2016-03-01

    We demonstrate for the first time a wearable biochemical sensor for monitoring alcohol consumption through the detection and quantification of a metabolite of ethanol, ethyl glucuronide (EtG). We designed and fabricated two co-planar sensors with gold and zinc oxide as sensing electrodes. We also designed a LED based reporting for the presence of EtG in the human sweat samples. The sensor functions on affinity based immunoassay principles whereby monoclonal antibodies for EtG were immobilized on the electrodes using thiol based chemistry. Detection of EtG from human sweat was achieved through chemiresistive sensing mechanism. In this method, an AC voltage was applied across the two coplanar electrodes and the impedance across the sensor electrodes was measured and calibrated for physiologically relevant doses of EtG in human sweat. EtG detection over a dose concentration of 0.001-100 μg/L was demonstrated on both glass and polyimide substrates. Detection sensitivity was lower at 1 μg/L with gold electrodes as compared to ZnO, which had detection sensitivity of 0.001 μg/L. Based on the detection range the wearable sensor has the ability to detect alcohol consumption of up to 11 standard drinks in the US over a period of 4 to 9 hours.

  19. Determinants of urinary 1-hydroxypyrene glucuronide in South Korean children.

    NARCIS (Netherlands)

    Lee, K.H.; Vermeulen, R.C.H.|info:eu-repo/dai/nl/216532620; Lenters, V.C.|info:eu-repo/dai/nl/314850171; Cho, S.H.; Strickland, P.; Kang, D.

    2009-01-01

    OBJECTIVES: This study was conducted to investigate the dominant sources of the urinary pyrene metabolite, 1-hydroxypyrene glucuronide (1-OHPG), in South Korean children. METHODS: Urine samples were collected from 102 non-smoking children (aged 10-14). Urinary 1-OHPG was assayed by synchronous

  20. Ethanol and ethyl glucuronide urine concentrations after ethanol-based hand antisepsis with and without permitted alcohol consumption.

    Science.gov (United States)

    Gessner, Stephan; Below, Elke; Diedrich, Stephan; Wegner, Christian; Gessner, Wiebke; Kohlmann, Thomas; Heidecke, Claus-Dieter; Bockholdt, Britta; Kramer, Axel; Assadian, Ojan; Below, Harald

    2016-09-01

    During hand antisepsis, health care workers (HCWs) are exposed to alcohol by dermal contact and by inhalation. Concerns have been raised that high alcohol absorptions may adversely affect HCWs, particularly certain vulnerable individuals such as pregnant women or individuals with genetic deficiencies of aldehyde dehydrogenase. We investigated the kinetics of HCWs' urinary concentrations of ethanol and its metabolite ethyl glucuronide (EtG) during clinical work with and without previous consumption of alcoholic beverages by HCWs. The median ethanol concentration was 0.7 mg/L (interquartile range [IQR], 0.5-1.9 mg/L; maximum, 9.2 mg/L) during abstinence and 12.2 mg/L (IQR, 1.5-139.6 mg/L; maximum, 1,020.1 mg/L) during alcohol consumption. During abstinence, EtG reached concentrations of up to 958 ng/mL. When alcohol consumption was permitted, the median EtG concentration of all samples was 2,593 ng/mL (IQR, 890.8-3,576 ng/mL; maximum, 5,043 ng/mL). Although alcohol consumption was strongly correlated with both EtG and ethanol in urine, no significant correlation for the frequency of alcoholic hand antisepsis was observed in the linear mixed models. The use of ethanol-based handrub induces measurable ethanol and EtG concentrations in urine. Compared with consumption of alcoholic beverages or use of consumer products containing ethanol, the amount of ethanol absorption resulting from handrub applications is negligible. In practice, there is no evidence of any harmful effect of using ethanol-based handrubs as much as it is clinically necessary. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  1. Ethyl glucuronide in vitreous humor and blood postmortem specimens: analysis by liquid chromatography-electrospray tandem mass spectrometry and interpreting results of neo-formation of ethanol

    Directory of Open Access Journals (Sweden)

    Sara Vezzoli

    2015-03-01

    Full Text Available Introduction. The determination of ethyl glucuronide (EtG, a stable and sensitive marker that is specific to alcohol intake, finds many applications both in the forensic toxicology and clinical fields. Aim. The aim of the study is to examine the possibility of using a cadaveric biological matrix, vitreous humor (VH, to determine EtG as a marker of recent ethanol use. Methods. The blood, taken from the femoral vein, and the VH were obtained from 63 autopsy cases. Analysis of the EtG was performed using an LC/MS/MS system. Analyses of the ethanol and putrefaction biomarkers, such as acetaldehyde and n-propanol, were performed using the HS-GC/FID technique in both the matrices. Results. In 17 cases, both ethanol and EtG were absent in both matrices.Nineteen cases presented ethanol in blood from 0.05 to 0.30 g/L, EtG-Blood concentration from 0.02 to 3.27 mg/L, and EtG-VH concentration from 0.01 mg/L to 2.88 mg/L. Thirteen cases presented ethanol in blood > 0.05 g/L but EtG concentration in blood and VH lower than 0.01 mg/L, are part of these 8 samples presented acetic aldehyde and n- propanol in blood or VH, means identification of putrefaction indicators. Fourteen cases presented ethanol in blood > 0.46 and EtG concentration in blood and VH higher than 0.01 mg/L. Conclusions. The determination of EtG in biological material is important in those cases where the intake of ethanol appears doubtful, as it allows us to exclude the possibility of any post-mortem formation of ethanol.

  2. Regiospecificity of Human UDP-glucuronosyltransferase Isoforms in Chalcone and Flavanone Glucuronidation Determined by Metal Complexation and Tandem Mass Spectrometry

    Science.gov (United States)

    Niemeyer, Emily D.; Brodbelt, Jennifer S.

    2013-01-01

    The glucuronidation of a series of chalcones (2'-hydroxychalcone, 2',4'-dihydroxychalcone, 3,2'-dihydroxychalcone, 4,2'-dihydroxychalcone, and cardamonin) and their corresponding cyclized flavanones (7-hydroxyflavanone, 3'-hydroxyflavanone, 4'-hydroxyflavanone, and alpinetin) by nine human UDP-glucuronosyltransferase (UGT) 1A enzymes was evaluated. A post-column metal complexation LC-MS/MS strategy was used successfully to produce characteristic mass spectrometric product ions that were utilized in combination with elution order trends to identify chalcone and flavanone monoglucuronides unambiguously, thus allowing determination of the regioselectivities of the UGT1A isoforms. The presence of hydroxy groups on the A or B-ring had a significant effect on the glucuronide product yield and the site where glucuronidation occurred. For example, for reaction with UGT1A9, formation of the 2'-O-glucuronide was increased for dihydroxychalcones with A-ring hydroxy substituents. In contrast, although UGT1A8 reacted with 3,2'-dihydroxychalcone and 4,2'-dihydroxychalcone to yield 2'-O-glucuronide products, the presence of a B-ring hydroxy group at the 4' position on cardamonin and 2',4'-dihydroxychalcone quenched the reaction at the OH-2' position. Moreover, the A-ring OH-4 group promoted glucuronidation at the 2' position for the reaction of 4,2'-dihydroxychalcone with UGT1A1 and 1A3. For UGT1A7, hydroxy group substituents on the chalcone A-ring also promoted cyclization and formation of the corresponding flavanone glucuronide. PMID:23713759

  3. A validated method for simultaneous determination of codeine, codeine-6-glucuronide, norcodeine, morphine, morphine-3-glucuronide and morphine-6-glucuronide in post-mortem blood, vitreous fluid, muscle, fat and brain tissue by LC-MS.

    Science.gov (United States)

    Frost, Joachim; Løkken, Trine N; Brede, Wenche R; Hegstad, Solfrid; Nordrum, Ivar S; Slørdal, Lars

    2015-04-01

    The toxicodynamics and, to a lesser degree, toxicokinetics of the widely used opiate codeine remain a matter of controversy. To address this issue, analytical methods capable of providing reliable quantification of codeine metabolites alongside codeine concentrations are required. This article presents a validated method for simultaneous determination of codeine, codeine metabolites codeine-6-glucuronide (C6G), norcodeine and morphine, and morphine metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in post-mortem whole blood, vitreous fluid, muscle, fat and brain tissue by high-performance liquid chromatography mass spectrometry. Samples were prepared by solid-phase extraction. The validated ranges were 1.5-300 ng/mL for codeine, norcodeine and morphine, and 23-4,600 ng/mL for C6G, M3G and M6G, with exceptions for norcodeine in muscle (3-300 ng/mL), morphine in muscle, fat and brain (3-300 ng/mL) and M6G in fat (46-4,600 ng/mL). Within-run and between-run accuracy (88.1-114.1%) and precision (CV 0.6-12.7%), matrix effects (CV 0.3-13.5%) and recovery (57.8-94.1%) were validated at two concentration levels; 3 and 150 ng/mL for codeine, norcodeine and morphine, and 46 and 2,300 ng/mL for C6G, M3G and M6G. Freeze-thaw and long-term stability (6 months at -80°C) was assessed, showing no significant changes in analyte concentrations (-12 to +8%). The method was applied in two authentic forensic autopsy cases implicating codeine in both therapeutic and presumably lethal concentration levels. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Determination of tapentadol and tapentadol-O-glucuronide in human serum samples by UPLC-MS/MS.

    Science.gov (United States)

    Hillewaert, Vera; Pusecker, Klaus; Sips, Luc; Verhaeghe, Tom; de Vries, Ronald; Langhans, Manfred; Terlinden, Rolf; Timmerman, Philip

    2015-02-15

    Tapentadol is a novel, centrally acting analgesic with 2 mechanisms of action, MOR agonism and noradrenaline (NA) reuptake inhibition in a single molecule. It is the first member of a new therapeutic class, MOR-NRI. A high throughput liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay was developed and validated for the quantitative analysis of tapentadol and its O-glucuronide metabolite in human serum. Simultaneous quantification was deemed to be challenging because of the large difference in concentrations between tapentadol and its O-glucuronide metabolite in clinical samples. Therefore, a method was established using a common processed sample, but with different injection volumes and chromatographic conditions for each analyte. Tapentadol and tapentadol-O-glucuronide were determined by protein precipitation of 0.100ml of the samples with acetonitrile. The internal standards used are D₆-tapentadol and D₆-tapentadol-O-glucuronide. The validated concentration range was 0.200-200 ng/ml (tapentadol) and 10.0-10,000 ng/ml (tapentadol-O-glucuronide). Chromatographic separation was achieved by gradient elution on a Waters Acquity UPLC BEH C18 (1.7 μm, 2.1 × 50 mm) column, with mobile phase consisting of 0.01 M ammonium formate (adjusted to pH 4 using formic acid) (A) and methanol (B). A separate injection was done for measurement of each analyte, with a different gradient and run time. The analytes were detected by using an electrospray ion source on a triple quadrupole mass spectrometer operating in positive ionization mode. The run time was 1.6 min for tapentadol and 1.5 min for tapentadol-O-glucuronide. The high sensitivity and acceptable performance of the assay allowed its application to the analysis of serum samples in clinical trials. The validated method was used for analysis of tapentadol in over 17,000 samples. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Protective effects of luteolin-7-O-beta-D-glucuronide methyl ester from the ethyl acetate fraction of Lycopi Herba against pro-oxidant reactive species and low-density lipoprotein peroxidation.

    Science.gov (United States)

    Lee, Min-Ja; Lee, Hye-Sook; Park, Sun-Dong; Moon, Hyung-In; Park, Won-Hwan

    2010-10-01

    In this study the potent scavenging activity of "Lycopi Herba" (LH) extract was studied using the following: evaluation of the total phenolics, measuring the antioxidant activity by Trolox equivalent antioxidant concentration, measuring the scavenging effects on reactive oxygen species, on reactive nitrogen species, and measuring the inhibitory effect on Cu(2+) induced human low-density lipoprotein oxidation in vitro. The ethyl acetate fraction from the LH extracts were found to have a potent scavenging activity against all of the reactive species tested, as well as an inhibitory effect on LDL oxidation. Therefore, we isolated and identified luteolin-7-O-beta-D-glucuronide methyl ester as the major compound from the ethyl acetate fraction of LH and their antioxidant activities were evaluated.

  6. Direct determination of glucuronide and sulfate of p-hydroxymethamphetamine in methamphetamine users' urine.

    Science.gov (United States)

    Shima, Noriaki; Tsutsumi, Hiroe; Kamata, Tooru; Nishikawa, Mayumi; Katagi, Munehiro; Miki, Akihiro; Tsuchihashi, Hitoshi

    2006-01-02

    Two conjugates of p-hydroxymethamphetamine (p-OHMA), p-OHMA-glucuronide (p-OHMA-Glu) and p-OHMA-sulfate (p-OHMA-Sul) have been identified in methamphetamine (MA) users' urine by using liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS-MS). The synthesis of p-OHMA-Glu and p-OHMA-Sul, and an LC-MS procedure for the simultaneous determination of MA and its four metabolites, amphetamine (AP), p-OHMA, p-OHMA-Glu and p-OHMA-Sul, in urine have also been established. After deproteinizing urine samples with methanol, LC-MS employing a C(18) semi-micro column with a gradient elution program provided the successful separations and MS determinations of these analytes within 20 min. Based on the established method, p-OHMA-Sul was detected at higher concentrations than p-OHMA-Glu in all of the three urine samples tested. These data suggest that sulfation is a major pathway in the MA phase II metabolism.

  7. Screening for Hazardous Drinking in Nursing Home Residents: Evaluating the Validity of the Current Cutoffs of the Alcohol Use Disorder Identification Test-Consumption Questions by Using Ethyl Glucuronide in Hair.

    Science.gov (United States)

    Dreher-Weber, Monika; Laireiter, Anton-Rupert; Kühberger, Anton; Kunz, Isabella; Yegles, Michel; Binz, Tina; Rumpf, Hans-Jürgen; Hoffmann, Rainer; Praxenthaler, Verena; Lang, Siegfried; Wurst, Friedrich M

    2017-09-01

    Because of physiological changes, elderly people are much more exposed to the adverse effects of alcohol. Therefore, hazardous drinking is defined at lower levels as compared to younger adults. This work aimed to evaluate the validity of the current cutoff levels of the Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) questions to detect hazardous drinking in the elderly by using ethyl glucuronide in hair (HEtG). In a border region between Austria and Germany, 344 nursing home residents were included from 33 of the 107 nursing homes. Residents were asked to answer the AUDIT-C questions, hair samples were obtained, and nursing staff members were asked for their assessments of the residents' alcohol consumption. Hair samples were analyzed for HEtG using gas chromatography-mass spectrometry. Receiver-operating characteristic (ROC) curve analysis was performed to determine the validity of cutoff values for the AUDIT-C to detect an alcohol consumption of ≥10 g of alcohol/d. A total of 11.3% of the nursing home residents (n = 344) drank ≥10 g of alcohol/d (4.9% >60 g of alcohol/d, 6.4% 10 to 60 g of alcohol/d, 88.7% alcohol/d)). For the drinking limit of ≥10 g of alcohol/d, ROC curve analysis showed a balanced sensitivity and specificity, with an AUDIT-C cutoff of ≥4 for men (sensitivity: 70%, specificity: 83.6%; AUC = 0.823, CI = 0.718 to 0.928, p alcohol consumption and evaluated 40% of the chronic-excessive alcohol consumers (>60 g of alcohol/d) as being abstinent. Our data suggest that an AUDIT-C cutoff of ≥4 for men and ≥2 for women can be recommended to detect the consumption of ≥10 g of alcohol/d in the elderly. Because the nursing staff to a large extent underestimates the alcohol consumption among nursing home residents, further teaching of the staff, improvement of screening instruments for the elderly, and the use of objective biomarkers might be helpful for recognizing hazardous drinking and can thus help improve the

  8. Isolation and determination of benzo(a)pyrene glucuronide and sulfate conjugates in soybean leaves

    Energy Technology Data Exchange (ETDEWEB)

    Negishi, T.; Nakano, M.; Kobayashi, S.; Kim, C.H.

    1987-08-01

    BaP is metabolized in mammalian systems by the mixed function oxidase system of liver microsomes. This system catalyzes the oxidation of BaP via epoxide intermediate to phenol, diol and quinone metabolites. One of these 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro-BaP is thought to act as the ultimate carcinogen by binding covalently to cellular DNA. It is also known that Cunninghamella elegans oxidized BaP to its phenol, diol and quinone metabolites. In addition, the alcohols were detected as glucuronide and sulfate conjugates. These metabolites are remarkably similar to those observed in higher organisms. On the other hand, some investigators have demonstrated that plants take up BaP and anthracene from soil or culture medium containing these compounds. This paper reports the finding that soybeans grown in BaP polluted soil take it up and metabolize to its phenol, diol and the glucuronide and sulfate conjugates of the alcohols.

  9. 78 FR 9938 - Ethyl Alcohol for Fuel Use: Determination of the Base Quantity of Imports

    Science.gov (United States)

    2013-02-12

    ... COMMISSION Ethyl Alcohol for Fuel Use: Determination of the Base Quantity of Imports AGENCY: United States... is equal to 7 percent of the U.S. domestic market for fuel ethyl alcohol during the 12-month period...'' of imports of fuel ethyl alcohol, and the Commission transmitted it determinations to the U.S...

  10. Steroid and steroid glucuronide profiles in urine during pregnancy determined by liquid chromatography-electrospray ionization-tandem mass spectrometry.

    Science.gov (United States)

    Jäntti, Sirkku E; Hartonen, Minna; Hilvo, Mika; Nygren, Heli; Hyötyläinen, Tuulia; Ketola, Raimo A; Kostiainen, Risto

    2013-11-13

    An ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-MS/MS) method was developed for the analysis of steroids and their glucuronides in urine samples. The method provides high sensitivity and fast analysis, as both steroids and their glucuronides can be analyzed directly without hydrolysis or complex sample preparation. The method was applied in profiling of targeted and nontargeted steroids and steroid glucuronides during pregnancy. The concentrations of 11 of 27 targeted steroids and steroid glucuronides and the concentrations of 25 nontargeted steroid glucuronides increased about 10-400 fold during the pregnancy. The concentrations of most of these 36 compounds began to increase in the first days of the pregnancy, increased gradually during the pregnancy, achieved a maximum in late pregnancy, and decreased sharply after delivery. Exceptionally, the concentrations of allopregnanolone and 17-hydroxypregnenolone started to increase later than those of the other steroids. Moreover, the concentrations of E2 glucuronides began to decrease one week before the delivery, in contrast to most of the steroids and steroid glucuronides, whose concentrations dropped sharply during the delivery. Concentrations of 34 compounds decreased noticeably when the subject was on sick leave owing a series of painful contractions. The results suggest that steroids and especially steroid glucuronides may provide a valuable diagnostic tool to follow the course of pregnancy. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Selective determination of ethyl acetate, acetone, ethanol, and methyl ethyl ketone using quartz crystal nanobalance combined with principle component analysis.

    Science.gov (United States)

    Mirmohseni, A; Razzaghi, M A; Pourata, R; Rastgouye-Hojagan, M; Zavareh, S

    2009-07-15

    Quartz crystal nanobalance (QCN) sensors are considered as powerful mass sensitive sensors to determine materials in the subnanogram level. In the current study a method based on QCN modified with polyethylene glycol (PEG) has been developed to determine organic vapors (ethyl acetate, acetone, ethanol and methyl ethyl ketone). The frequency shift of QCN was found to be linear against analytes concentrations in the range between 4 to 35 mg/L for acetone vapor and 4-70 mg/L for 3 other vapors. The correlation coefficients for ethyl acetate, acetone, ethanol, and methyl ethyl ketone were 0.9971, 0.9976, 0.9984 and 0.9927, respectively. The principal component analysis was also utilized to process the frequency response data of the organic vapors. Using principal component analysis, it was found that over 95% of the data variance could still be explained by use of two principal components (PC1 and PC2). Subsequently, the successful discrimination of ethyl acetate and other compounds was possible through the principal component analysis of the transient responses of the PEG-modified QCN sensor.

  12. Buprenorphine metabolites, buprenorphine-3-glucuronide and norbuprenorphine-3-glucuronide, are biologically active

    Science.gov (United States)

    Brown, Sarah M.; Holtzman, Michael; Kim, Thomas; Kharasch, Evan D.

    2012-01-01

    Background The long-lasting high affinity opioid buprenorphine has complex pharmacology including ceiling effects with respect to analgesia and respiratory depression. Plasma concentrations of the major buprenorphine metabolites norbuprenorphine, buprenorphine-3-glucuronide, and norbuprenorphine-3-glucuronide approximate or exceed those of the parent drug. Buprenorphine glucuronide metabolites pharmacology is undefined. This investigation determined binding and pharmacological activity of the two glucuronide metabolites, and in comparison with buprenorphine and norbuprenorphine. Methods Competitive inhibition of radioligand binding to human mu, kappa, delta opioid and nociceptin receptors was used to determine glucuronide binding affinities for these receptors. Common opiate effects were assessed in vivo in Swiss Webster mice. Antinociception was assessed using a tail-flick assay, respiratory effects were measured using unrestrained whole-body plethysmography, and sedation was assessed by inhibition of locomotion measured by open-field testing. Results Buprenorphine-3-glucuronide had high affinity for human mu (Ki = 4.9±2.7 pM), delta (Ki = 270±0.4 nM), and nociceptin (Ki = 36±0.3 μM) but not kappa receptors. Norbuprenorphine-3-glucuronide had affinity for human kappa (Ki = 300±0.5 nM) and nociceptin (Ki= 18±0.2 μM) but not mu or delta receptors. At the dose tested, buprenorphine-3-glucuronide had a small antinociceptive effect. Neither glucuronide had significant effects on respiratory rate, but norbuprenorphine-3-glucuronide decreased tidal volume. Norbuprenorphine-3-glucuronide also caused sedation. Conclusions Both glucuronide metabolites of buprenorphine are biologically active at doses relevant to metabolite exposures which occur after buprenorphine. Activity of the glucuronides may contribute to the overall pharmacology of buprenorphine. PMID:22037640

  13. Genetic influences on individual differences in nicotine glucuronidation.

    Science.gov (United States)

    Lessov-Schlaggar, Christina N; Benowitz, Neal L; Jacob, Peyton; Swan, Gary E

    2009-10-01

    Nicotine and its primary oxidative metabolites are metabolized in part by glucuronidation. Genetic variation in UGT isoenzymes that catalyze glucuronidation activity suggests that variation in glucuronidation rate is in part genetically determined. The relative contribution of genetic and environmental sources to individual differences in the rate of glucuronidation of nicotine, cotinine, and trans-3'-hydroxycotinine was estimated in a twin study of nicotine pharmacokinetics. Glucuronidation rate was defined using measures that either accounted for variability in renal clearance or assumed the same relative renal clearance of parent drug and glucuronide conjugate across individuals. The former definition resulted in highly correlated nicotine and cotinine glucuronidation measures that were substantially influenced by the combined effect of additive (heritable) and non-additive (dominant and epistatic) genetic effects. These findings suggest that genetic variation in UGT isoenzymes that act in additive and interactive ways is an important determinant of individual variability in nicotine and cotinine metabolism via glucuronidation pathways.

  14. Determination of ethyl carbamate in some fermented Korean foods and beverages.

    Science.gov (United States)

    Kim, Y K; Koh, E; Chung, H J; Kwon, H

    2000-06-01

    Ethyl carbamate has been associated with cancer for several decades. It is mainly found in fermented foods and beverages. In view of the importance of fermented foods in the Korean diet and the significant level of ethyl carbamate expected, we determined ethyl carbamate concentrations in some of the staple food items and estimated the daily intake for the Korean population. Ethyl carbamate in commercial samples of kimchi, soy sauce, vinegar, soybean paste, and alcoholic beverages were determined by gas chromatography-mass spectrometry/selective ion monitoring (GC-MS/SIM). Homemade soy sauce and kimchi were also analysed. The maximum ethyl carbamate concentrations observed were 73 micrograms/kg in soy sauce, 7.9 micrograms/kg in soybean paste, 2.5 micrograms/l in vinegar, 16.2 micrograms/kg in kimchi and 15.4 mu/l in Korean traditional alcoholic beverages. Combining these values with the average daily food intake data, we estimated that the maximum daily exposure of Korean population to ethyl carbamate is 2.8 micrograms/day, which is not a negligible amount considering the 'virtually safe dose' derived by animal experiment ranges between 1.2 and 4.8 micrograms/day. It would be desirable to closely monitor ethyl carbamate levels in Korean foods and to find ways to reduce the daily intake.

  15. Determination of Bioactive Components of Ethyl Acetate Fraction of Punica granatum Rind Extract

    OpenAIRE

    J. Sangeetha; K. Vijayalakshmi

    2011-01-01

    Punica granatum belongs to a Punicaceae family. The Punica granatum is valued as a powerful medicinal plant and used in folk medicines. Hence the present investigation was carried out to determine the possible chemical components from ethyl acetate fraction of Punica granatum rind extract by GC-MS Technique. This analysis revealed that ethyl acetate fraction of Punica granatum rind extract contain Pyrogallol (41.88%), 5-Hydroxymethylfurfural (14.10%), D-Allose (9.17%), 2-Methoxy-1, 4-Benzened...

  16. Simultaneous determination of morinidazole, its N-oxide, sulfate, and diastereoisomeric N(+)-glucuronides in human plasma by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Gao, Ruina; Zhong, Dafang; Liu, Ke; Xia, Yu; Shi, Rongwei; Li, Hua; Chen, Xiaoyan

    2012-11-01

    Morinidazole is a new third-generation 5-nitroimidazole antimicrobial drug. To investigate the pharmacokinetic profiles of morinidazole and its major metabolites in humans, a liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination of morinidazole, its N-oxide metabolite (M4-1), a sulfate conjugate (M7), and two diastereoisomeric N(+)-glucuronides (M8-1 and M8-2) in human plasma. A simple acetonitrile-induced protein precipitation was employed to extract five analytes and internal standard metronidazole from 50μL human plasma. To avoid the interference from the in-source dissociation of the sulfate and achieve the baseline-separation of diastereoisomeric N(+)-glucuronides, all the analytes were separated from each other with the mobile phase consisting of 10mM ammonium formate and acetonitrile using gradient elution on a Hydro-RP C(18) column (50mm×2mm, 4μm) with a total run time of 5min. The API 4000 triple quadrupole mass spectrometer was operated under the multiple reaction-monitoring mode using the electrospray ionization technique. The developed method was linear in the concentration ranges of 10.0-12,000ng/mL for morinidazole, 1.00-200ng/mL for M4-1, 2.50-500ng/mL for M7, 3.00-600ng/mL for M8-1, and 10.0-3000ng/mL for M8-2. The intra- and inter-day precisions for each analyte met the accepted value. Results of the stability of morinidazole and its metabolites in human plasma were also presented. The method was successfully applied to the clinical pharmacokinetic studies of morinidazole injection in healthy subjects, patients with moderate hepatic insufficiency, and patients with severe renal insufficiency, respectively. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Validation of a rapid and sensitive LC-MS/MS method for determination of exemestane and its metabolites, 17β-hydroxyexemestane and 17β-hydroxyexemestane-17-O-β-D-glucuronide: application to human pharmacokinetics study.

    Directory of Open Access Journals (Sweden)

    Ling-Zhi Wang

    Full Text Available A novel, rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS method was developed and validated for the evaluation of exemestane pharmacokinetics and its metabolites, 17β-dihydroexemestane (active metabolite and 17β-dihydroexemestane-17-O-β-D-glucuronide (inactive metabolite in human plasma. Their respective D3 isotopes were used as internal standards. Chromatographic separation of analytes was achieved using Thermo Fisher BDS Hypersil C18 analytic HPLC column (100 × 2.1 mm, 5 μm. The mobile phase was delivered at a rate of 0.5 mL/min by gradient elution with 0.1% aqueous formic acid and acetonitrile. The column effluents were detected by API 4000 triple quadrupole mass spectrometer using electrospray ionisation (ESI and monitored by multiple reaction monitoring (MRM in positive mode. Mass transitions 297 > 121 m/z, 300 > 121 m/z, 299 > 135 m/z, 302 > 135 m/z, 475 > 281 m/z, and 478 > 284 m/z were monitored for exemestane, exemestane-d3, 17β-dihydroexemestane, 17β-dihydroexemestane-d3, 17β-dihydroexemestane-17-O-β-D-glucuronide, and 17β-dihydroexemestane-17-O-β-D-glucuronide-d3 respectively. The assay demonstrated linear ranges of 0.4-40.0 ng/mL, for exemestane; and 0.2-15.0 ng/mL, for 17β-dihydroexemestane and 17β-dihydroexemestane-17-O-β-D-glucuronide, with coefficient of determination (r2 of > 0.998. The precision (coefficient of variation were ≤10.7%, 7.7% and 9.5% and the accuracies ranged from 88.8 to 103.1% for exemestane, 98.5 to 106.1% for 17β-dihydroexemestane and 92.0 to 103.2% for 17β-dihydroexemestane-17-O-β-D-glucuronide. The method was successfully applied to a pharmacokinetics/dynamics study in breast cancer patients receiving exemestane 25 mg daily orally. For a representative patient, 20.7% of exemestane in plasma was converted into 17β-dihydroexemestane and 29.0% of 17β-dihydroexemestane was inactivated as 17β-dihydroexemestane-17-O-β-D-glucuronide 24 hours after ingestion of

  18. LC-H-1 NMR used for determination of the elution order of S-naproxen glucuronide isomers in two isocratic reversed-phase LC-systems

    DEFF Research Database (Denmark)

    Mortensen, R. W.; Corcoran, O.; Cornett, Claus

    2001-01-01

    The reactive metabolite S-naproxen-beta -1-O-acyl glucuronide was purified from human urine using solid phase extraction (SPE) and preparative HPLC. The structure was confirmed by 600 MHz H-1 NMR. Directly coupled 600 MHz HPLC-H-1 NMR was used to assign the peaks in chromatograms obtained when...... analysing a sample containing S-naproxen aglycone and the 1-, 2-, 3-, and 4-isomers of S-naproxen-beta -1-O-acyl glucuronide in two simple isocratic reversed phase HPLC-systems. Using mobile phase I (50 mM formate buffer pH 5.75/acetonitrile 75:25 v/v) the elution order was: 4-O-acyl isomers, beta -1-O......-acyl glucuronide, 3-O-acyl isomers, 2-O-acyl isomers, and S-naproxen aglycone. Using mobile phase II (25 mM potassium phosphate pH 7.40/acetonitrile 80:20 v/v) the elution order was: alpha/beta -4-O-acyl isomers, S-naproxen aglycone, beta -1-O-acyl glucuronide, 3-O-acyl isomers, and alpha/beta -2-O-acyl isomers...

  19. Characterization of raloxifene glucuronidation. Potential role of UGT1A8 genotype on raloxifene metabolism in vivo

    OpenAIRE

    Sun, Dongxiao; Jones, Nathan R.; Manni, Andrea; Lazarus, Philip

    2013-01-01

    Raloxifene is a 2nd-generation selective estrogen receptor modulator used for the prevention and treatment of osteoporosis and the prevention of breast cancer in postmenopausal women. Raloxifene is extensively metabolized by glucuronidation to form raloxifene-6-glucuronide (ral-6-Gluc) and raloxifene-4′-glucuronide (ral-4′-Gluc). The goal of the present study was to determine whether functional polymorphisms in active UGTs could play a role in altered raloxifene glucuronidation in vivo. Using...

  20. Development of a UPLC–MS/MS method for determining ɣ-hydroxybutyric acid (GHB) and GHB glucuronide concentrations in hair and application to forensic cases

    DEFF Research Database (Denmark)

    Wang, Xin; Johansen, Sys Stybe; Linnet, Kristian

    2016-01-01

    We present a series of forensic cases measuring concentrations in hair of γ-hydroxybutyric acid (GHB) and its glucuronide. The compounds were extracted from hair by incubation for 1.5 h in a 25:25:50 (v/v/v) mixture of methanol/acetonitrile/2 mM ammonium formate (8 % acetonitrile, pH 5.3). The co......We present a series of forensic cases measuring concentrations in hair of γ-hydroxybutyric acid (GHB) and its glucuronide. The compounds were extracted from hair by incubation for 1.5 h in a 25:25:50 (v/v/v) mixture of methanol/acetonitrile/2 mM ammonium formate (8 % acetonitrile, pH 5...

  1. Tequila volatile characterization and ethyl ester determination by solid phase microextraction gas chromatography/mass spectrometry analysis.

    Science.gov (United States)

    Vallejo-Cordoba, Belinda; González-Córdova, Aarón Fernando; del Carmen Estrada-Montoya, María

    2004-09-08

    Solid phase microextraction (SPME) and gas chromatography were used for tequila volatile characterization and ethyl ester quantitation. Several factors determined the differences in tequila volatile profiles obtained by the SPME technique, namely, sampling mode, fiber coating, and fiber exposure time. Each of these factors determined the most suitable conditions for the analysis of volatile profiles in tequila. Volatile extraction consisted of placing 40 mL of tequila in a sealed vial kept at 40 degrees C. A poly(dimethylsiloxane) fiber was immersed in the liquid for 60 min and desorbed for 5 min into the gas chromatograph. The identified volatiles by mass spectrometry were mainly alcohols, esters, and ketones. The calibration curves for ethyl hexanoate, octanoate, and decanoate followed linear relationships with highly significant (p tequila samples. Quantitative differences in ethyl esters were found for the four most commonly known tequila types: silver, gold, aged, and extra-aged.

  2. Ultrasound-assisted emulsification-microextraction for the sensitive determination of ethyl carbamate in alcoholic beverages.

    Science.gov (United States)

    Liao, Qie Gen; Li, Wei Hong; Luo, Lin Guang

    2013-08-01

    A method based on ultrasound-assisted emulsification-microextraction (USAEME) was proposed in this contribution for the determination of ethyl carbamate (EC) in alcoholic beverages using gas chromatography coupled to triple quadrupole mass spectrometry. To achieve the determination of EC in alcoholic beverages, the influences on the extraction efficiency of type and volume of extraction solvent, temperature, ionic strength, alcohol content, and extraction time were studied, once the extraction solvent had been selected. The optimized conditions were 200.0 μL of chloroform at 30 °C during 5 min with 15% (m/v) sodium chloride addition. The detection limit, relative standard deviations, linear range, and recoveries under the optimized conditions were 0.03 μg L(-1), 4.2-6.1%, 0.1-50.0 μg L(-1), and 80.5-87.9%, respectively. Moreover, the feasibility of the present method was also validated by real samples. To the best of our knowledge, this is the first time that USAEME has been applied to determine a strongly hydrophilic compound in alcoholic beverages.

  3. Inhibition of 2-methoxyestradiol glucuronidation by probenecid.

    Science.gov (United States)

    Qian, Yuli; Sherbini, Ahmad; Matin, Bahar; Zhao, Yanli; Castellot, John; Greenblatt, David J

    2015-11-01

    2-Methoxyestradiol (2ME2), a metabolite of estradiol, has antitumour activity in vitro. However, potential clinical applicability has been limited by low oral bioavailability. Probenecid was evaluated in vitro as an inhibitor of 2ME2 glucuronidation for purposes of enhancing 2ME2 oral bioavailability. Human liver microsomes were used to determine kinetic parameters for transformation of 2ME2 to its glucuronide metabolites (M1, M2) and inhibition of the reactions by probenecid. M1 and M2 formation from 2ME2 proceeded with features of substrate inhibition. Probenecid inhibited metabolite formation, with mean inhibition constant (Ki ) values of 0.9 and 2.6 mM, respectively. Inhibition was reversible, with mixed competitive-non-competitive characteristics. The Ki values for probenecid inhibition of 2ME2 glucuronide formation, when compared to maximum probenecid plasma concentrations anticipated clinically, indicate that probenecid co-administration has the potential to augment systemic plasma levels of 2ME2 after oral dosage in humans. © 2015 Royal Pharmaceutical Society.

  4. Determination of coumarin, vanillin, and ethyl vanillin in vanilla extract products: liquid chromatography mass spectrometry method development and validation studies.

    Science.gov (United States)

    de Jager, Lowri S; Perfetti, Gracia A; Diachenko, Gregory W

    2007-03-23

    A LC-MS method was developed for the determination of coumarin, vanillin, and ethyl vanillin in vanilla products. Samples were analyzed using LC-electrospray ionization (ESI)-MS in the positive ionization mode. Limits of detection for the method ranged from 0.051 to 0.073 microg mL(-1). Using the optimized method, 24 vanilla products were analyzed. All samples tested negative for coumarin. Concentrations ranged from 0.38 to 8.59 mg mL(-1) (x =3.73) for vanillin and 0.33 to 2.27 mg mL(-1) (x =1.03) for ethyl vanillin. The measured concentrations are compared to values calculated using UV monitoring and to results reported in a similar survey in 1988. Analytical results, method precision, and accuracy data are presented.

  5. Determination of benzene, toluene ,ethyl benzene and xylene (BTEX) in ambient air painting workshops car compared to the air surrounding residential areas during winter 1394 in Yazd city

    National Research Council Canada - National Science Library

    MH Salmani; MH Ehrampoush; MH Mosadeg; S MH Sharifi

    2017-01-01

    Abstract Title: Determination of benzene, toluene ,ethyl benzene and xylene (BTEX) in ambient air painting workshops car compared to the air surrounding residential areas during winter 1394 in Yazd city...

  6. Blood-brain distribution of morphine-6-glucuronide in sheep

    DEFF Research Database (Denmark)

    Villesen, H H; Foster, D J R; Upton, R N

    2006-01-01

    At present there are few data regarding the rate and extent of brain-blood partitioning of the opioid active metabolite of morphine, morphine-6-glucuronide (M6G). In this study the cerebral kinetics of M6G were determined, after a short-term intravenous infusion, in chronically instrumented consc...... conscious sheep....

  7. Spectrophotometric Determination of Nitrogen Oxides in the Air with 2-N-Ethyl-5-Naphthol-7-Sulfonic Acid

    Science.gov (United States)

    Huang, Y.; Shi, W.; Zhang, C.; Wen, H.

    2017-09-01

    For the determination of nitrogen oxides in the air, the structure of diazo and coupling compounds was studied and tested by experiments. The conditions and methods of diazo and coupling reactions were investigated. Furthermore, a spectrophotometric method using sulfanilamide as a diazo compound and 2-N-ethyl-5-naphthol-7-sulfonic acid (N-ethyl J acid) as a coupling compound was proposed. The maximum absorption wavelength of sulfanilamide-Nethyl J acid azo compound was at 478 nm. The molar absorptivity was 4.31 × 104 L/(mol × cm) with a recovery of 98.7-100.9% and RSD of 1.85%. For nitrogen oxides, the determinate limit of this measurement was 0.015 mg/m3 and the determinate range 0.024-2.0 mg/m3. Moreover, a high degree of correlation was observed between the results obtained by the proposed method and the standard methods. The proposed method can be easily applied to determine nitrogen oxides in the air.

  8. The chemiluminescence determination of 2-chloroethyl ethyl sulfide using luminol-AgNO3-silver nanoparticles system

    Science.gov (United States)

    Maddah, Bozorgmehr; Shamsi, Javad; Barsang, Mehran Jam; Rahimi-Nasrabadi, Mehdi

    2015-05-01

    A highly sensitive chemiluminescence (CL) method for the determination of 2-chloroethyl ethyl sulfide (2-CEES) was presented. It was found that 2-chloroethyl ethyl sulfide (2-CEES) could inhibit the CL of the luminol-AgNO3 system in the presence of silver nanoparticles in alkaline solution, which made it applicable for determination of 2-CEES. The presented method is simple, convenient, rapid and sensitive. Under the optimized conditions, the calibration curve was linear in the range of 0.0001-1 ng mL-1, with the correlation coefficient of 0.992; while the limit of detection (LOD), based on signal-to-noise ratio (S/N) of 3, was 6 × 10-6 ng mL-1. Also, the relative standard deviation (RSD, n = 5) for determination of 2-CEES (0.50 ng mL-1) was 3.1%. The method was successfully applied for the determination of 2-CEES in environmental aqueous samples.

  9. [Simultaneous determination of ethyl carbamate and chloropropanols in flavorings by gas chromatography-triple quadrupole tandem mass spectrometry].

    Science.gov (United States)

    Xu, Xiaomin; He, Huali; Ruan, Yudi; Huang, Baifen; Zhang, Jingshun; Cai, Zengxuan; Ren, Yiping

    2013-11-01

    A simultaneous determination method for ethyl carbamate (EC) and chloropropanols (3-monochloropropane-1, 2-diol (3-MCPD) and 2-monochloropropane-1, 3-diol (2-MCPD)) in flavorings was developed by gas chromatography-triple quadrupole tandem mass spectrometry (GC-MS/MS). After spiked with internal standard, the sample was extracted by matrix solid-phase dispersion extraction technique with an Extrelut NT column. Hexane was used to wash the fat soluble matrix interferences and then an ethyl acetate-ethyl ether (20: 80, v/v) mixture was added to elute the analytes. The concentrated extract was detected by GC-MS/MS in multiple reaction monitoring (MRM) mode. The limits of detection (LODs) were 2, 5 and 5 microg/kg for EC, 3-MCPD and 2-MCPD, respectively. The linear ranges were 5 - 1 000 microg/kg (r = 0.9997), 10-1000 microg/kg (r = 0.999 1) and 10-1000 microg/kg (r = 0.999 5) for EC, 3-MCPD and 2-MCPD, respectively. In soy sauce, yellow rice wine, salami sauce and flavoring of instant noodle matrices, the recoveries (RSDs, n = 7) in MRM mode at the levels of 20, 100 and 400 microg/kg were 87.7%-104% (4.3%-10.7%), 90.1%-109% (2.6%-10.2%), and 90.9%-103% (3.0%-9.5%), respectively. EC, 3-MCPD and 2-MCPD were found in some real samples of the soy sauce, wine and flavoring of instant noodle. EC or 3-MCPD was found in some of the salami samples. The method is accurate, fast and suitable for the simultaneous determination of EC, 3-MCPD and 2-MCPD in flavorings.

  10. A New Rapid In Vitro Assay for Assessing Reactivity of Acyl Glucuronides.

    Science.gov (United States)

    Zhong, Sheng; Jones, Russell; Lu, Wenzhe; Schadt, Simone; Ottaviani, Giorgio

    2015-11-01

    Idiosyncratic drug toxicity is a major challenge for the pharmaceutical industry since complex and multifactorial steps are involved, the dose-dependency is unclear, and its occurrence is not reliably predictable. Whereas the exact mechanisms leading to idiosyncratic toxicity remain elusive in many cases, there are often hints at the involvement of reactive metabolites, such as acyl glucuronides formed by conjugation of carboxylic acids with glucuronic acid. Because the patient-related susceptibilities leading to idiosyncratic toxicity are not sufficiently understood, the best option for the pharmaceutical industry is to minimize drug-related risk factors such as potential acyl glucuronide formation. Here, we describe a rapid in vitro assay for the assessment of the reactivity of acyl glucuronides, on the basis of acyl glucuronide migration, that can support the selection of low-risk drug candidates in the drug discovery phase. Twenty marketed compounds with a wide range of half-lives were tested, their acyl glucuronide migration rates were determined and compared with the half-lives of the respective acyl glucuronides. Ranking of acyl glucuronide stability using this method compared well with the results from existing methodologies. With this method, migration rates >20% would indicate higher risk of reactivity. This simpler approach using the acyl glucuronide migration rate is not dependent on authentic standards, therefore eliminating the requirement for either lengthy chemical synthesis or in vitro biosynthesis and purification of the 1-O-β-glucuronide. This methodology provides a rapid in vitro assay to assess acyl glucuronide stability and reactivity that is well suited for use early in the drug discovery phase. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  11. Trace determination of ethyl methanesulfonate in Viracept 250 mg tablets by gas chromatography-mass spectrometry.

    Science.gov (United States)

    Rebiere, H; Maggio, A-F; Gimeno, P; Levaillant, D; Civade, C; Bonnet, P-A; Tissier, M-H

    2008-02-01

    Ethyl methanesulfonate (EMS) is a potential human mutagenic and carcinogenic compound which has been found by Roche laboratories in nelfinavir mesylate, the active pharmaceutical ingredient of Viracept. In order to verify the quality of the medicinal product, a gas chromatographic method using mass spectrometry detection was developed for the trace analysis of EMS in Viracept 250 mg tablets from Roche laboratories. Combined with suitable sample preparation including a liquid/liquid extraction this method allows the EMS quantification with a reporting limit of 5 ppm. The extract is injected on a gas chromatographic system with a CP624-CB capillary column. Selected Ion Monitoring mode was used for the EMS quantification. Some validation elements of the method are reported. The validation study was performed over a range from 5 ppm to 100 ppm.

  12. Determination of Ethyl Carbamate in Alcoholic Beverages and Fermented Foods Sold in Korea.

    Science.gov (United States)

    Ryu, Dayeon; Choi, Bogyoung; Kim, Eunjoo; Park, Seri; Paeng, Hwijin; Kim, Cho-Il; Lee, Jee-Yeon; Yoon, Hae Jung; Koh, Eunmi

    2015-09-01

    Ethyl carbamate (EC) classified as a probable human carcinogen (Group 2A) is naturally formed in alcoholic beverages and fermented foods during fermentation process and/or during storage. The objective of this study was to analyze EC in 34 food items including 14 alcoholic beverages and 20 fermented foods sold in Korea. Each food was collected from 18 supermarkets in 9 metropolitan cities in Korea, and then made into composite. According to food composition and alcohol content, samples were divided into four matrices such as apple juice, milk, Soju (liquor containing about 20% alcohol), and rice porridge. The maximum EC value of 151.06 µg/kg was found in Maesilju (liquor made from Maesil and Soju). Whisky and Bokbunjaju (Korean black raspberry wine) contained 9.90 µg/kg and 6.30 µg/kg, respectively. EC was not detected in other alcoholic beverages. Of 20 fermented foods, Japanese-style soy sauce had highest level of 15.59 µg/kg and traditional one contained 4.18 µg/kg. Soybean paste had 1.18 µg/kg, however, EC was not found in other fermented foods.

  13. Determination of Ethyl Carbamate in Alcoholic Beverages and Fermented Foods Sold in Korea

    Science.gov (United States)

    Ryu, Dayeon; Choi, Bogyoung; Kim, Eunjoo; Park, Seri; Paeng, Hwijin; Kim, Cho-il; Lee, Jee-yeon; Yoon, Hae Jung

    2015-01-01

    Ethyl carbamate (EC) classified as a probable human carcinogen (Group 2A) is naturally formed in alcoholic beverages and fermented foods during fermentation process and/or during storage. The objective of this study was to analyze EC in 34 food items including 14 alcoholic beverages and 20 fermented foods sold in Korea. Each food was collected from 18 supermarkets in 9 metropolitan cities in Korea, and then made into composite. According to food composition and alcohol content, samples were divided into four matrices such as apple juice, milk, Soju (liquor containing about 20% alcohol), and rice porridge. The maximum EC value of 151.06 µg/kg was found in Maesilju (liquor made from Maesil and Soju). Whisky and Bokbunjaju (Korean black raspberry wine) contained 9.90 µg/kg and 6.30 µg/kg, respectively. EC was not detected in other alcoholic beverages. Of 20 fermented foods, Japanese-style soy sauce had highest level of 15.59 µg/kg and traditional one contained 4.18 µg/kg. Soybean paste had 1.18 µg/kg, however, EC was not found in other fermented foods. PMID:26483888

  14. Ontogeny of midazolam glucuronidation in preterm infants

    NARCIS (Netherlands)

    S.N. de Wildt (Saskia); G.L. Kearns (Greg); D.J. Murry (Darryl); G. Koren (Gideon); J.N. van den Anker (John)

    2010-01-01

    textabstractPurpose: In preterm infants, the biotransformation of midazolam (M) to 1-OH-midazolam (OHM) by cytochrome P450 3A4 (CYP3A4) is developmentally immature, but it is currently unknown whether the glucuronidation of OHM to 1-OH-midazolam glucuronide (OHMG) is also decreased. The aim of our

  15. Identification of human UDP-glucuronosyltransferase isoform(s) responsible for the C-glucuronidation of phenylbutazone.

    Science.gov (United States)

    Nishiyama, Takahito; Kobori, Tomihiro; Arai, Kouji; Ogura, Kenichiro; Ohnuma, Tomokazu; Ishii, Kazuo; Hayashi, Kenichiro; Hiratsuka, Akira

    2006-10-01

    Glucuronidation is a major metabolic pathway in the biotransformation of many xenobiotics and endogeneous compounds. There have been many studies on the formation of O-, N- or S-glucuronides and identification of the UDP-glucuronosyltransferase (UGT) isoforms responsible for the formation of these glucuronides. However, there is no information available on which UGT isoform(s) catalyzes C-glucuronidation. In the present study, 16 human UGTs (UGTs 1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B10, 2B11, 2B15, 2B17 and 2B28) were cloned and expressed in baculovirus-infected insect cells and investigated to determine their C-glucuronidating activity toward phenylbutazone (PB). Among the UGT isoforms investigated, only UGT1A9 catalyzed PB C-glucuronidation. Human liver and kidney microsomes, which are well known to express UGT1A9, had C-glucuronidating activity toward PB. However, the jejunum, which did not express UGT1A9, had no C-glucuronidating activity. These results demonstrate for the first time that PB C-glucuronidation is catalyzed by only UGT1A9.

  16. Pharmacokinetics of acetaminophen, codeine, and the codeine metabolites morphine and codeine-6-glucuronide in healthy Greyhound dogs

    OpenAIRE

    KuKanich, Butch

    2010-01-01

    The purpose of this study was to determine the pharmacokinetics of codeine and the active metabolites morphine and codeine-6-glucuronide after IV codeine administration and the pharmacokinetics of acetaminophen (APAP), codeine, morphine, and codeine-6-glucuronide after oral administration of combination product containing acetaminophen and codeine to dogs.

  17. A new chemiluminescence method for determination of clonazepam and diazepam based on 1-Ethyl-3-Methylimidazolium Ethylsulfate/copper as catalyst

    Science.gov (United States)

    Chaichi, M. J.; Alijanpour, S. O.

    2014-01-01

    A novel chemiluminescence (CL) reaction, Benzodiazepines-H2O2-1-Ethyl-3-Methylimidazolium Ethylsulfate/copper, for determination of clonazepam and diazepam at nanogram per milliliter level in batch-type system have been described. The method relies on the catalytic effect of 1-Ethyl-3-Methylimidazolium Ethylsulfate/copper on the chemiluminescence reaction of Benzodiazepines, the oxidation of Benzodiazepines with hydrogen peroxide in natural medium. The influences of various experimental parameters such as solution pH, the ratio of 1-Ethyl-3 Methylimidazolium ethylsulfate concentration to copper ion, the type of buffer and the concentration of CL reagents were investigated. Under the optimum condition, the proposed method was satisfactorily applied for the determination of these drugs in tablets and urine without the interference of their potential impurities.

  18. Toxicological investigation of Di(ethyl-hexyl) phthalate in rats. The determination of doses-without-effect for various enzyme parameters

    NARCIS (Netherlands)

    Jansen EHJM; van den Ham WA; de Fluiter P; Laan CA; van Leeuwen FXR

    1992-01-01

    Two animal experiments are described in which male rates have been exposed to di(2-ethyl-hexyl)phthalate (DEHP) for 2 and 4 weeks. A number of enzyme parameters in liver homogenates have been determined which have a relation with the proliferation of peroxisomes in hepatocytes, such as palmitoyl

  19. Relative importance of intestinal and hepatic glucuronidation-impact on the prediction of drug clearance.

    Science.gov (United States)

    Cubitt, Helen E; Houston, J Brian; Galetin, Aleksandra

    2009-05-01

    To assess the extent of intestinal and hepatic glucuronidation in vitro and resulting implications on glucuronidation clearance prediction. Alamethicin activated human intestinal (HIM) and hepatic (HLM) microsomes were used to obtain intrinsic glucuronidation clearance (CL(int,UGT)) for nine drugs using substrate depletion. The in vitro extent of glucuronidation (fm(UGT)) was determined using P450 and UGT cofactors. Utility of hepatic CL(int) for the prediction of in vivo clearance was assessed. fm(UGT) (8-100%) was comparable between HLM and HIM with the exception of troglitazone, where a nine-fold difference was observed (8% and 74%, respectively). Scaled intestinal CL(int,UGT) (per g tissue) was six- and nine-fold higher than hepatic for raloxifene and troglitazone, respectively, and comparable to hepatic for naloxone. The remaining drugs had a higher hepatic than intestinal CL(int,UGT) (average five-fold). For all drugs with P450 clearance, hepatic CL(int,CYP) was higher than intestinal (average 15-fold). Hepatic CL(int,UGT) predicted on average 22% of observed in vivo CL(int); with the exception of raloxifene and troglitazone, where the prediction was only 3%. Intestinal glucuronidation should be incorporated into clearance prediction, especially for compounds metabolised by intestine specific UGTs. Alamethicin activated microsomes are useful for the assessment of intestinal glucuronidation and fm(UGT) in vitro.

  20. Determination of Monomers Reactivity Ratios in Ethyl Acrylate-Methacrylic Acid Copolymerization by Off-Line 1H NMR

    Directory of Open Access Journals (Sweden)

    Samaneh Ashenagar

    2017-03-01

    Full Text Available The physical, chemical and mechanical properties of polymer systems depend on the micro-structural characteristics of their macromolecular chains. Along with the most characteristic kinetic parameters in copolymerization reactions are the reactivity ratios, which give a clear idea of the average composition and the monomer sequence distribution in copolymer systems. This research studies the solution radical copolymerization of methacrylic acid (MAA-ethyl acrylate (EA system at low conversion with 2,2'-azobisisobutyronitrile (AIBN as thermal initiator at 60°C in deuterated dimethyl sulfoxide (DMSO-d6 as a reaction solvent. In this case, the monomer reactivity ratios were determined using linear off-line 1H nuclear magnetic resonance spectroscopy (1H NMR methods such as Mayo-Louis, Finemann-Ross, Inverted Finemann-Ross , Ezrielev-Brokhina-Roskin, Joshi-Joshi, Kelen-Tudos, extended Kelen- Tudos, Mao-Huglin at low and high conversions. The next estimation process in off-line 1H NMR methods were performed by applying techniques based on ordinary least square (OLS and generalized least square (GLS. The results showed that the GLS approach compared to the OLS increased regression coefficients (R2 and the order of magnitude of parameter variances obtained from GLS was many times lower than that obtained from OLS. In addition, the monomer reactivity ratios obtained by the Mao-Huglin method and the GLS approach showed the best linear estimation.

  1. Determination of the release mechanism of Theophylline from pellets coated with Surelease®-A water dispersion of ethyl cellulose.

    Science.gov (United States)

    Kazlauske, Jurgita; Cafaro, Maria Margherita; Caccavo, Diego; Marucci, Mariagrazia; Lamberti, Gaetano; Barba, Anna Angela; Larsson, Anette

    2017-08-07

    The aim of this study was to investigate the water transport over free standing films based on the aqueous ethyl cellulose (EC) coating Surelease® and the drug (Theophylline) release mechanism from coated pellets. It was found that the main drug release rate from pellets was controlled by a diffusion mechanism. However, the drug release rate was altered by addition of sodium chloride to the external release medium. A decrease in the drug release rate when sodium chloride is added to the release medium has traditionally been used to indicate an osmotic drug release mechanism. However, our findings that the release rate decreased by sodium chloride addition could be explained by sodium chloride diffusing through the coating layer into the inner parts of the pellets, decreasing the solubility of Theophylline. This gave a reduced drug concentration gradient over the coating layer and thus a slower release rate. Furthermore, this study shows, as expected, that the transport of water through Surelease® films into the pellets was faster than the transport out of Theophylline (approx. seven times), which was the reason why the pellets were swelling during the release. It was also shown that the drug release rate, determined for both whole dose release and for single pellets, decreased with increasing thickness (from 16 to 51μm) of the coating layer controlling the drug release rate. Copyright © 2017. Published by Elsevier B.V.

  2. Development and validation of a HPLC–QTOF-MS method for the determination of GHB-β-O-glucuronide and GHB-4-sulfate in plasma and urine

    DEFF Research Database (Denmark)

    Mehling, Lena-Maria; Piper, Thomas; Dib, Josef

    2017-01-01

    -Sulf in urine, the reference standard material of GHB-Sulf was synthesized, together with its deuterated analogue, GHB-Sulf-d6. This reference standard material, together with GHB-Gluc and GHB-Gluc-d4, was employed to develop and validate a quantitative method for determining both target analytes in plasma......Gamma-hydroxybutyric acid (GHB) is used as a so-called knock-out drug in drug-facilitated sexual assault. Due to GHB’s short detection window in blood and urine, crime verification remains problematic in many cases. Phase II metabolites can enhance the detectability and prolong the detection window...... weeks, and both phase II metabolites were found to be stable under refrigerated conditions. This method proved to be suitable for this purpose, and allowed for the first time the analysis and quantification of two different GHB metabolites from plasma and urine samples....

  3. Identification and characterization of human UDP-glucuronosyltransferases responsible for the in-vitro glucuronidation of arctigenin.

    Science.gov (United States)

    Xin, Hong; Xia, Yang-Liu; Hou, Jie; Wang, Ping; He, Wei; Yang, Ling; Ge, Guang-Bo; Xu, Wei

    2015-12-01

    This study aimed to characterize the glucuronidation pathway of arctigenin (AR) in human liver microsomes (HLM) and human intestine microsomes (HIM). HLM and HIM incubation systems were employed to catalyse the formation of AR glucuronide. The glucuronidation activity of commercially recombinant UGT isoforms towards AR was screened. A combination of chemical inhibition assay and kinetic analysis was used to determine the UGT isoforms involved in the glucuronidation of AR in HLM and HIM. AR could be extensively metabolized to one mono-glucuronide in HLM and HIM. The mono-glucuronide was biosynthesized and characterized as 4'-O-glucuronide. UGT1A1, 1A3, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7 and 2B17 participated in the formation of 4'-O-G, while UGT2B17 demonstrated the highest catalytic activity in this biotransformation. Both kinetic analysis and chemical inhibition assays demonstrated that UGT1A9, UGT2B7 and UGT2B17 played important roles in AR-4'-O-glucuronidation in HLM. Furthermore, HIM demonstrated moderate efficiency for AR-4'-O-glucuronidation, implying that AR may undergo a first-pass metabolism during the absorption process. UGT1A9, UGT2B7 and UGT2B17 were the major isoforms responsible for the 4'-O-glucuronidation of AR in HLM, while UGT2B7 and UGT2B17 were the major contributors to this biotransformation in HIM. © 2015 Royal Pharmaceutical Society.

  4. Efflux Transport Characterization of Resveratrol Glucuronides in UDP-Glucuronosyltransferase 1A1 Transfected HeLa Cells: Application of a Cellular Pharmacokinetic Model to Decipher the Contribution of Multidrug Resistance-Associated Protein 4.

    Science.gov (United States)

    Wang, Shuai; Li, Feng; Quan, Enxi; Dong, Dong; Wu, Baojian

    2016-04-01

    Resveratrol undergoes extensive metabolism to form biologically active glucuronides in humans. However, the transport mechanisms for resveratrol glucuronides are not fully established. Here, we aimed to characterize the efflux transport of resveratrol glucuronides using UGT1A1-overexpressing HeLa cells (HeLa1A1 cells), and to determine the contribution of multidrug resistance-associated protein (MRP) 4 to cellular excretion of the glucuronides. Two glucuronide isomers [i.e., resveratrol 3-O-glucuronide (R3G) and resveratrol 4'-O-glucuronide (R4'G)] were excreted into the extracellular compartment after incubation of resveratrol (1-100 μM) with HeLa1A1 cells. The excretion rate was linearly related to the level of intracellular glucuronide, indicating that glucuronide efflux was a nonsaturable process. MK-571 (a dual inhibitor of UGT1A1 and MRPs) significantly decreased the excretion rates of R3G and R4'G while increasing their intracellular levels. Likewise, short-hairpin RNA (shRNA)-mediated silencing of MRP4 caused a significant reduction in glucuronide excretion but an elevation in glucuronide accumulation. Furthermore, β-glucuronidase expressed in the cells catalyzed the hydrolysis of the glucuronides back to the parent compound. A cellular pharmacokinetic model integrating resveratrol transport/metabolism with glucuronide hydrolysis/excretion was well fitted to the experimental data, allowing derivation of the efflux rate constant values in the absence or presence of shRNA targeting MRP4. It was found that a large percentage of glucuronide excretion (43%-46%) was attributed to MRP4. In conclusion, MRP4 participated in cellular excretion of R3G and R4'G. Integration of mechanistic pharmacokinetic modeling with transporter knockdown was a useful method to derive the contribution percentage of an exporter to overall glucuronide excretion. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  5. In silico prediction of acyl glucuronide reactivity

    Science.gov (United States)

    Potter, Tim; Lewis, Richard; Luker, Tim; Bonnert, Roger; Bernstein, Michael A.; Birkinshaw, Timothy N.; Thom, Stephen; Wenlock, Mark; Paine, Stuart

    2011-11-01

    Drugs and drug candidates containing a carboxylic acid moiety, including many widely used non-steroidal anti-inflammatory drugs (NSAIDs) are often metabolized to form acyl glucuronides (AGs). NSAIDs such as Ibuprofen are amongst the most widely used drugs on the market, whereas similar carboxylic acid drugs such as Suprofen have been withdrawn due to adverse events. Although the link between these AG metabolites and toxicity is not proven, there is circumstantial literature evidence to suggest that more reactive acyl glucuronides may, in some cases, present a greater risk of exhibiting toxic effects. We wished therefore to rank the reactivity of potential new carboxylate-containing drug candidates, and performed kinetic studies on synthetic acyl glucuronides to benchmark our key compounds. Driven by the desire to quickly rank the reactivity of compounds without the need for lengthy synthesis of the acyl glucuronide, a correlation was established between the degradation half-life of the acyl glucuronide and the half life for the hydrolysis of the more readily available methyl ester derivative. This finding enabled a considerable broadening of chemical property space to be investigated. The need for kinetic measurements was subsequently eliminated altogether by correlating the methyl ester hydrolysis half-life with the predicted 13C NMR chemical shift of the carbonyl carbon together with readily available steric descriptors in a PLS model. This completely in silico prediction of acyl glucuronide reactivity is applicable within the earliest stages of drug design with low cost and acceptable accuracy to guide intelligent molecular design. This reactivity data will be useful alongside the more complex additional pharmacokinetic exposure and distribution data that is generated later in the drug discovery process for assessing the overall toxicological risk of acidic drugs.

  6. Synthesis, structure characterization, and enzyme screening of clenbuterol glucuronides.

    Science.gov (United States)

    Alonen, Anna; Gartman, Minna; Aitio, Olli; Finel, Moshe; Yli-Kauhaluoma, Jari; Kostiainen, Risto

    2009-07-12

    Two clenbuterol O-glucuronide diastereomers were synthesized by the Koenigs-Knorr reaction. Structures and glucuronidation sites of the glucuronides were characterized by tandem mass spectrometry and nuclear magnetic resonance spectroscopy. The two diastereomers were used as standard compounds in studies of stereoselective glucuronidation of clenbuterol with liver microsomes from different species and with 15 human recombinant UDP-glucuronosyltransferases. In this study, chemical and enzymatic reactions produced only O-glucuronides of clenbuterol, although on the basis of the chemical structure of the aglycone, both O- and N-glucuronides of clenbuterol could be formed. Differences in the production of diastereomers of clenbuterol glucuronides were observed among liver microsomes from the various animals. Dog and bovine liver microsomes were significantly active, and also stereoselective, each producing only one but a different diastereomer. Liver microsomes from rabbit and rat were also rather actively glucuronidating clenbuterol, but human, pig, and moose liver microsomes produced only minor amounts of glucuronides. Human liver microsomes produced only one clenbuterol glucuronide diastereomer, and the same was true of the human UDP-glucuronosyltransferases that were active (formation of glucuronide: 1A9 > 1A10 > 1A7). The marked differences in the stereoselective glucuronidation of clenbuterol show that UDP-glucuronosyltransferases in the livers of different animals do not have the same functions, activities, or distribution. This needs to be taken into account, particularly in toxicology testing.

  7. Assessment of the stability of the ethanol metabolite ethyl sulfate in standardised degradation tests.

    Science.gov (United States)

    Halter, Claudia C; Laengin, Andreas; Al-Ahmad, Ali; Wurst, Friedrich M; Weinmann, Wolfgang; Kuemmerer, Klaus

    2009-04-15

    Ethyl sulfate (EtS) is a non-oxidative metabolite of ethanol, used for forensic purposes as an ethanol consumption marker in addition to the ethanol metabolite ethyl glucuronide (EtG) which after certain scientific publications is prone to biological degradation. As ethanol is widely consumed in many western cultures, knowledge about the stability of ethyl sulfate against biodegradation is of importance for forensic investigations-where EtS until now was thought to be stable against bacterial degradation. Using standardized test methods from the panel of OECD tests, the stability of EtS against bacterial degradation was assessed in this study. These experiments showed that EtS was stable in the closed bottle test (CBT) (OECD 301 D), but not in the manometric respiratory test (MRT) (OECD 301 F) with higher bacterial density. With respect to forensic investigations the assumption of EtS stability could be disproved and the possibility of bacterial degradation of EtS should be taken into account when alcohol uptake some hours prior to death needs to be ruled out by determination of alcohol consumption markers in putrefied corpses, where ethanol concentration could have been generated post-mortem by fermentation processes.

  8. Interindividual variability in the glucuronidation of (S) oxazepam contrasted with that of (R) oxazepam.

    Science.gov (United States)

    Patel, M; Tang, B K; Grant, D M; Kalow, W

    1995-10-01

    Although conjugation with glucuronic acid is a major process for converting many xenobiotics into hydrophilic, excretable metabolites, relatively little has been reported concerning interindividual variability of glucuronidation in human populations. Oxazepam, a therapeutically active metabolite of diazepam, is one of a number of C3-hydroxylated benzodiazepines for which glucuronide conjugation is the predominant pathway of biotransformation. The drug is normally formulated as a racemic mixture of inactive (R) and active (S) enantiomers. In the present study we have investigated the use of oxazepam as a potential probe drug for studying the variability of glucuronide conjugation, and for demonstrating the extent to which genetic factors may be responsible. In preliminary studies we determined oxazepam pharmacokinetics metabolite profiles after administration of racemic (R,S) oxazepam to eleven human volunteers. The (S) glucuronide was preferentially formed and excreted in nine of the eleven subjects. The ratios of (S) to (R) glucuronide metabolites (S/R ratios) were 3.87 +/- 0.79 (mean +/- SD) and 3.52 +/- 0.60 in urine and plasma, respectively. However, both ratios were significantly lower in two subjects (p reaction may reflect defects at the genetic level, leading to structural changes in the isozyme(s) of UDP-glucuronyltransferase that catalyse this reaction.

  9. New Flavonol Glucuronides from the Flower Buds of Syzygium aromaticum (Clove).

    Science.gov (United States)

    Ryu, Byeol; Kim, Hye Mi; Lee, Jin Su; Lee, Chan Kyu; Sezirahiga, Jurdas; Woo, Jeong-Hwa; Choi, Jung-Hye; Jang, Dae Sik

    2016-04-20

    Repeated chromatography of the EtOAc-soluble fraction from the 70% EtOH extract of the flower buds of Syzygium aromaticum (clove) led to the isolation and characterization of four new flavonol glucuronides, rhamnetin-3-O-β-d-glucuronide (1), rhamnazin-3-O-β-d-glucuronide (2), rhamnazin-3-O-β-d-glucuronide-6″-methyl ester (3), and rhamnocitrin-3-O-β-d-glucuronide-6″-methyl ester (4), together with 15 flavonoids (5-19) having previously known chemical structures. The structures of the new compounds 1-4 were determined by interpretation of spectroscopic data, particularly by 1D- and 2D-NMR studies. Six flavonoids (6, 7, 9, 14, 18, and 19) were isolated from the flower buds of S. aromaticum for the first time in this study. The flavonoids were examined for their cytotoxicity against human ovarian cancer cells (A2780) using MTT assays. Among the isolates, pachypodol (19) showed the most potent cytotoxicity on A2780 cells with an IC50 value of 8.02 μM.

  10. Determination of benzene, toluene ,ethyl benzene and xylene (BTEX in ambient air painting workshops car compared to the air surrounding residential areas during winter 1394 in Yazd city .

    Directory of Open Access Journals (Sweden)

    MH Salmani

    2017-01-01

    Full Text Available Abstract Title: Determination of benzene, toluene ,ethyl benzene and xylene (BTEX in ambient air painting workshops car compared to the air surrounding residential areas during winter 1394 in Yazd city . MH.Salmani1 , MH. Ehrampoush2, MH.Mosadegh3 , SMH. Sharifi4* 1Depatment of Health , School of Health , Shahid Sadoughi University of Medical Sciences,YAZD, IRAN 2Depatment of Health , School of Health , Shahid Sadoughi University of Medical Sciences,YAZD, IRAN 3Depatment of Pharmacology , School of Pharmacy , Shahid Sadoughi University of Medical Sciences,YAZD, IRAN 4Student of M.Sc Environmental Health Enginiering , international branch , Shahid Sadoughi University of Medical Sciences,YAZD, IRAN ( Responder Introduction: benzene, toluene , ethyl benzene and xylene (BTEX such as volatile organic compounds and air pollutants are important that have similar chemical and physical properties. The compounds in solvents, petrochemicals and colors plentiful and are released and even in small amounts as well as the risks to industry employees and the surrounding residential areas along their industry (50 meters radius around. The purpose of this study was to determine the amount of these pollutants in ambient air car paint workshops, as well as residential areas around the city of Yazd. Materials and Methods: In this study, environmental air from air painting workshops Yazd city cars in winter 1394 and residential areas surrounding air workshop by Tedlar bags and personal sampling pump were collected and using gas chromatography (GC / FID analysis and evaluation of data were then with statistical software SPSS-16 were analyzed. Results: The results showed that the average concentration and standard deviation of pollutants benzene, toluene , ethyl benzene and xylene in the ambient air painting workshops are (2/14 ± 0/73 , (4/09 ± 1/97, (1/08 ± 0/290 and (3/05 ± 1/00 ppm  and the average concentration and standard deviation of pollutants benzene

  11. Glucuronidated Flavonoids in Neurological Protection: Structural Analysis and Approaches for Chemical and Biological Synthesis.

    Science.gov (United States)

    Docampo, Maite; Olubu, Adiji; Wang, Xiaoqiang; Pasinetti, Giulio; Dixon, Richard A

    2017-09-06

    Both plant and mammalian cells express glucuronosyltransferases that catalyze glucuronidation of polyphenols such as flavonoids and other small molecules. Oral administration of select polyphenolic compounds leads to the accumulation of the corresponding glucuronidated metabolites at μM and sub-μM concentrations in the brain, associated with amelioration of a range of neurological symptoms. Determining the mechanisms whereby botanical extracts impact cognitive wellbeing and psychological resiliency will require investigation of the modes of action of the brain-targeted metabolites. Unfortunately, many of these compounds are not commercially available. This article describes the latest approaches for the analysis and synthesis of glucuronidated flavonoids. Synthetic schemes include both standard organic synthesis, semisynthesis, enzymatic synthesis and use of synthetic biology utilizing heterologous enzymes in microbial platform organisms.

  12. Multiplexed Targeted Quantitative Proteomics Predicts Hepatic Glucuronidation Potential.

    Science.gov (United States)

    Margaillan, Guillaume; Rouleau, Michèle; Klein, Kathrin; Fallon, John K; Caron, Patrick; Villeneuve, Lyne; Smith, Philip C; Zanger, Ulrich M; Guillemette, Chantal

    2015-09-01

    Phase II metabolism is prominently governed by UDP-glucuronosyltransferases (UGTs) in humans. These enzymes regulate the bioactivity of many drugs and endogenous small molecules in many organs, including the liver, a major site of regulation by the glucuronidation pathway. This study determined the expression of hepatic UGTs by targeted proteomics in 48 liver samples and by measuring the glucuronidation activity using probe substrates. It demonstrates the sensitivity and accuracy of nano-ultra-performance liquid chromatography with tandem mass spectrometry to establish the complex expression profiles of 14 hepatic UGTs in a single analysis. UGT2B7 is the most abundant UGT in our collection of livers, expressed at 69 pmol/mg microsomal proteins, whereas UGT1A1, UGT1A4, UGT2B4, and UGT2B15 are similarly abundant, averaging 30-34 pmol/mg proteins. The average relative abundance of these five UGTs represents 81% of the measured hepatic UGTs. Our data further highlight the strong relationships in the expression of several UGTs. Most notably, UGT1A4 correlates with most measured UGTs, and the expression levels of UGT2B4/UGT2B7 displayed the strongest correlation. However, significant interindividual variability is observed for all UGTs, both at the level of enzyme concentrations and activity (coefficient of variation: 45%-184%). The reliability of targeted proteomics quantification is supported by the high correlation between UGT concentration and activity. Collectively, these findings expand our understanding of hepatic UGT profiles by establishing absolute hepatic concentrations of 14 UGTs and further suggest coregulated expression between most abundant hepatic UGTs. Data support the value of multiplexed targeted quantitative proteomics to accurately assess specific UGT concentrations in liver samples and hepatic glucuronidation potential. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  13. Simultaneous determination of plasma epinephrine and norepinephrine using an integrated strategy of a fully automated protein precipitation technique, reductive ethylation labeling and UPLC-MS/MS.

    Science.gov (United States)

    Ji, Chengjie; Walton, Justin; Su, Yi; Tella, Max

    2010-06-18

    A novel, automated, simple, sensitive, specific, accurate, precise and high-throughput liquid chromatography tandem mass spectrometry (LC-MS/MS)-based method has been developed for simultaneous determination of epinephrine (E) and norepinephrine (NE) in plasma by using the combination of a fully automated protein precipitation technique for plasma sample preparation, reductive ethylation labeling with UPLC-MS/MS. A simple protein precipitation procedure was used to clean up 50 microL calibration samples prepared in stripped human plasma and 50 microL quality control plasma samples containing 25 microL plasma and 25 microL stabilizing additives. The supernatants were subsequently dried down and then reconstituted with commercially available and cost-effective reductive ethylation labeling reagents, followed by UPLC-MS/MS analysis. All liquid handling during sample preparation was automated using a Hamilton MicroLab Star Robotic workstation, which included the preparation of standards and quality control samples, shaking of 96-well plates, adding and transferring liquids. Processing time, which included the preparation of standards and quality control samples, protein precipitation and reductive ethylation labeling, is less than 2 h per 96-well plate. The chromatographic run time is 3.5 min per sample. The limits of detection of UPLC-MS/MS-based methods for E and NE, with/without reductive ethylation labeling, are 0.025/0.40 and 0.025/2.00 ng mL(-1), respectively. Reductive ethylation labeling of amino groups of E and NE affords 16 and 80 times increased detection sensitivity of corresponding native counterparts during the UPLC-MS/MS analysis. The linearity of this method was established from 0.05 to 25 ng mL(-1) for E and NE with accuracy and precision within 15% at all concentrations. The intra-run and inter-run assay accuracy (%RE) and coefficient of variations (CV%) are all within 15% for all QC samples prepared in commercially purchased plasma samples. 2010

  14. The development of a high-performance liquid chromatography-tandem mass spectrometric method for simultaneous quantification of morphine, morphine-3-β-glucuronide, morphine-6-β-glucuronide, hydromorphone, and normorphine in serum.

    Science.gov (United States)

    Sartori, David; Lewis, Tamorah; Breaud, Autumn; Clarke, William

    2015-12-01

    Development and validation of a selective, robust high-performance liquid chromatography-tandem mass spectrometric (HPLC/MS-MS) method for the quantification of morphine, morphine-3-β-glucuronide, morphine-6-β-glucuronide, hydromorphone, and normorphine in human serum. Drug-free human serum samples spiked with morphine, morphine-3-β-glucuronide, morphine-6-β-glucuronide, hydromorphone, and normorphine were prepared by protein precipitation using methanol containing the internal standards. Samples were injected onto a Thermo Scientific AccuCore PFP column for chromatographic separation. Detection was achieved using a Thermo Scientific TSQ Vantage mass spectrometer. Assay validation followed the new Clinical and Laboratory Standards Institute (CLSI) C62-A guidelines. The analytical measuring range for all analytes was determined to be 5 to 1000 ng/mL. Intra- and inter-assay precision for three quality control levels were ≤ 7.0% and ≤ 13.5%, respectively. Carryover, stability, linearity, matrix effects, extraction and processing efficiency and method comparison characteristics were acceptable relative to the CLSI C62 guidelines. The validation of this HPLC-MS/MS method demonstrated a robust and rapid assay for the quantification of morphine, morphine-3-β-glucuronide, morphine-6-β-glucuronide, hydromorphone, and normorphine. Copyright © 2015 The Canadian Society of Clinical Chemists. All rights reserved.

  15. Solid phase extraction, multidimensional gas chromatography mass spectrometry determination of four novel aroma powerful ethyl esters. Assessment of their occurrence and importance in wine and other alcoholic beverages.

    Science.gov (United States)

    Campo, Eva; Cacho, Juan; Ferreira, Vicente

    2007-01-26

    A method for the quantitative determination of four powerful aromatic ethyl esters recently identified in some wines has been developed, validated and applied to the determination of these compounds in different samples of wine, whisky and brandy. Ethyl 2-, 3-, and 4-methylpentanoate and ethyl cyclohexanoate are extracted from 100ml of sample by solid phase extraction (SPE) on a 200mg LiChrolut EN bed. Major compounds are eliminated by rinsing with a water-methanol (50:50) solution containing 1% sodium bicarbonate, and analytes are eluted with 1.5ml of dichloromethane. Fifty microlitres of this extract are then injected in a multidimensional gas chromatography-mass spectromety (GC-GC-MS) system. Recoveries in the SPE are quantitative. Method repeatability is satisfactory (5-12% for a 5-10ngl(-1) level, and less than 7% for 25-50ngl(-1) level), the method linearity holds along the whole range of occurrence of analytes (2-2700ngl(-1)), and the signal is independent on the matrix. Method detection limits are below 1ngl(-1) in all cases. Results suggest that these compounds are formed by the slow esterification with ethanol of the corresponding acids formed by different microorganisms. The levels of these compounds are above the corresponding thresholds in most samples of aged wines or distillates, but are particularly high in some sweet wines, whiskeys and brandies where they may constitute the most important contributors to the sweet-fruity notes reaching concentrations up to 85-350 times higher than the corresponding odor thresholds.

  16. Amino acid positions 69-132 of UGT1A9 are involved in the C-glucuronidation of phenylbutazone.

    Science.gov (United States)

    Nishiyama, Takahito; Fujishima, Miki; Masuda, Yasuhiro; Izawa, Tadashi; Ohnuma, Tomokazu; Ogura, Kenichiro; Hiratsuka, Akira

    2008-10-01

    Phenylbutazone (PB) is known to be biotransformed to its O- and C-glucuronide. Recently, we reported that PB C-glucuronide formation is catalyzed by UGT1A9. Interestingly, despite UGT1A8 sharing high amino acid sequence identity with UGT1A9, UGT1A8 had no PB C-glucuronidating activity. In the present study, we constructed eight UGT1A9/UGT1A8 chimeras and evaluated which region is important for PB C-glucuronide formation. All of the chimeras and UGT1A8 and UGT1A9 had 7-hydroxy-(4-trifluoromethyl)coumarin (HFC) O-glucuronidating activity. The K(m) values for HFC glucuronidation of UGT1A8, UGT1A9 and their chimeras were divided into two types, UGT1A8 type (high K(m)) and UGT1A9 type (low K(m)), and these types were determined according to whether their amino acids at positions 69-132 were those of UGT1A8 or UGT1A9. Likewise, PB O-glucuronidating activity was also detected by all of the chimeras, and their K(m) values were divided into two types. On the contrary, PB C-glucuronidating activity was detected by UGT1A9((1-132))/1A8((133-286)), UGT1A9((1-212))/1A8((213-286)), UGT1A8((1-68))/1A9((69-286)), and UGT1A8((1-68))/1A9((69-132))/1A8((133-286)) chimeras. The region 1A9((69-132)) was common among chimeras having PB C-glucuronidating activity. Of interest is that UGT1A9((1-68))/1A8((69-132))/1A9((133-286)) had lost PB C-glucuronidation activity, but retained activities of PB and HFC O-glucuronidation. These results strongly suggested that amino acid positions 69-132 of UGT1A9 are responsible for chemoselectivity for PB and affinity to substrates such as PB and HFC.

  17. Characterization of raloxifene glucuronidation: potential role of UGT1A8 genotype on raloxifene metabolism in vivo.

    Science.gov (United States)

    Sun, Dongxiao; Jones, Nathan R; Manni, Andrea; Lazarus, Philip

    2013-07-01

    Raloxifene is a second-generation selective estrogen receptor modulator used for the prevention and treatment of osteoporosis and the prevention of breast cancer in postmenopausal women. Raloxifene is extensively metabolized by glucuronidation to form raloxifene-6-glucuronide (ral-6-Gluc) and raloxifene-4'-glucuronide (ral-4'-Gluc). The goal of the present study was to determine whether functional polymorphisms in active UGTs could play a role in altered raloxifene glucuronidation in vivo. Using homogenates from HEK293 UGT-overexpressing cell lines, raloxifene was shown to be glucuronidated primarily by the hepatic UGTs 1A1 and 1A9 and the extra-hepatic UGTs 1A8 and 1A10; no detectable raloxifene glucuronidation activity was found for UGT2B enzymes. Functional UGT1A1 transcriptional promoter genotypes were significantly (Ptrend = 0.005) associated with ral-6-Gluc formation in human liver microsomes, and, consistent with the decreased raloxifene glucuronidation activities observed in vitro with cell lines overexpressing UGT1A8 variants, the UGT1A8*2 variant was significantly (P = 0.023) correlated with total raloxifene glucuronide formation in human jejunum homogenates. While ral-4'-Gluc exhibited 1:100th the anti-estrogenic activity of raloxifene itself as measured by binding to the estrogen receptor, raloxifene glucuronides comprised about 99% of the circulating raloxifene dose in raloxifene-treated subjects, with ral-4'-Gluc comprising ~70% of raloxifene glucuronides. Plasma ral-6-Gluc (Ptrend = 0.0025), ral-4'-Gluc (Ptrend = 0.001), and total raloxifene glucuronides (Ptrend = 0.001) were increased in raloxifene-treated subjects who were predicted slow metabolizers [UGT1A8 (*1/*3)] versus intermediate metabolizers [UGT1A8 (*1/*1) or UGT1A8 (*1/*2)] versus fast metabolizers [UGT1A8 (*2/*2). These data suggest that raloxifene metabolism may be dependent on UGT1A8 genotype and that UGT1A8 genotype may play an important role in overall response to raloxifene. ©2013

  18. Characterization of raloxifene glucuronidation. Potential role of UGT1A8 genotype on raloxifene metabolism in vivo

    Science.gov (United States)

    Sun, Dongxiao; Jones, Nathan R; Manni, Andrea; Lazarus, Philip

    2014-01-01

    Raloxifene is a 2nd-generation selective estrogen receptor modulator used for the prevention and treatment of osteoporosis and the prevention of breast cancer in postmenopausal women. Raloxifene is extensively metabolized by glucuronidation to form raloxifene-6-glucuronide (ral-6-Gluc) and raloxifene-4′-glucuronide (ral-4′-Gluc). The goal of the present study was to determine whether functional polymorphisms in active UGTs could play a role in altered raloxifene glucuronidation in vivo. Using homogenates from HEK293 UGT-overexpressing cell lines, raloxifene was shown to be glucuronidated primarily by the hepatic UGTs 1A1 and 1A9 and the extra-hepatic UGTs 1A8 and 1A10; no detectable raloxifene glucuronidation activity was found for UGT2B enzymes. Functional UGT1A1 transcriptional promoter genotypes were significantly (ptrend=0.005) associated with ral-6-Gluc formation in human liver microsomes, and, consistent with the decreased raloxifene glucuronidation activities observed in vitro with cell line over-expressing UGT1A8 variants, the UGT1A8*2 variant was significantly (p=0.023) correlated with total raloxifene glucuronide formation in human jejunum homogenates. While ral-4′-Gluc exhibited 1/100th the anti-estrogenic activity of raloxifene itself as measured by binding to the estrogen receptor, raloxifene glucuronides comprised ∼99% of the circulating raloxifene dose in raloxifene-treated subjects, with ral-4′-Gluc comprising ∼70% of raloxifene glucuronides. Plasma ral-6-Gluc (ptrend=0.0025), ral-4′-Gluc (ptrend=0.001), and total raloxifene glucuronides (ptrend=0.001) were increased in raloxifene-treated subjects who were predicted slow metabolizers [UGT1A8 (*1/*3)] vs intermediate metabolizers [UGT1A8 (*1/*1) or UGT1A8 (*1/*2)] vs fast metabolizers [UGT1A8 (*2/*2). These data suggest that raloxifene metabolism may be dependent on UGT1A8 genotype and that UGT1A8 genotype may play an important role in overall response to raloxifene. PMID:23682072

  19. Bisphenol A glucuronidation in patients with Parkinson's disease.

    Science.gov (United States)

    Landolfi, Annamaria; Troisi, Jacopo; Savanelli, Maria Cristina; Vitale, Carmine; Barone, Paolo; Amboni, Marianna

    2017-12-01

    Bisphenol A (BPA) is a widely distributed estrogen-mimetic molecule, with well-established effects on the dopaminergic system. It can be found in canned food, dental sealants, thermal paper, etc. BPA undergoes liver conjugation with glucuronic acid and is subsequently excreted in the urine. In the present study we quantified the concentration of free and conjugated Bisphenol A in blood of patients affected by Parkinson Disease, using their spouses as controls. An interview was performed to determine possible confounders in BPA exposure. Free and conjugated BPA were quantified by gas chromatography coupled with mass spectrometry. Parkinson's Disease patients carried a statistically significant lower amount of conjugated Bisphenol A compared to controls. The two populations were mostly homogeneous in terms of exposure to possible Bisphenol A sources. The only exceptions were exposure to canned tuna and canned tomatoes PD patients consumed significantly more of both (pBisphenol A glucuronidation was found after stratification by typology of anti-Parkinson's drug taken and after conversion to the Levodopa Equivalent Daily Dose. BPA glucuronidation was decreased in patients with Parkinson disease. The possible unique mechanisms underlying Bisphenol A metabolism in PD patients deserve further elucidation. Moreover, further study is needed to assess a possible BPA role in Parkinson's Disease pathogenesis, due to its documented dopaminergic toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ethyl alcohol containing ethyl acetate. 584.200... Ethyl alcohol containing ethyl acetate. The feed additive ethyl alcohol containing ethyl acetate meets... having had added the equivalent of 4.25 gallons of 100 percent ethyl acetate. It is used in accordance...

  1. Genetic Influences on Individual Differences in Nicotine Glucuronidation

    National Research Council Canada - National Science Library

    Lessov-Schlaggar, Christina N; Benowitz, Neal L; Jacob, Peyton; Swan, Gary E

    2009-01-01

    .... The relative contribution of genetic and environmental sources to individual differences in the rate of glucuronidation of nicotine, cotinine, and trans-32- hydroxycotinine was estimated in a twin...

  2. Glucuronidation, a new metabolic pathway for pyrrolizidine alkaloids.

    Science.gov (United States)

    He, Yu-Qi; Yang, Li; Liu, Hui-Xin; Zhang, Jiang-Wei; Liu, Yong; Fong, Alan; Xiong, Ai-Zhen; Lu, Yan-Liu; Yang, Ling; Wang, Chang-Hong; Wang, Zheng-Tao

    2010-03-15

    Pyrrolizidine alkaloids (PAs) possess significant hepatotoxicity to humans and animals after metabolic activation by liver P450 enzymes. Metabolism pathways of PAs have been studied for several decades, including metabolic activation, hydroxylation, N-oxidation, and hydrolysis. However, the glucuronidation of intact PAs has not been investigated, although glucuronidation plays an important role in the elimination and detoxication of xenobiotics. In this study, PAs glucuronidation was investigated, and three important points were found. First, we demonstrated that senecionine (SEN)-a representative hepatotoxic PA-could be conjugated by glucuronic acid via an N-glucuronidation reaction catalyzed by uridine diphosphate glucuronosyl transferase in human liver microsomes. Second, glucuronidation of SEN was catalyzed not only by human but also other animal species and showed significant species differences. Rabbits, cattle, sheep, pigs, and humans showed the significantly higher glucuronidation activity than mice, rats, dogs, and guinea pigs on SEN. Kinetics of SEN glucuronidation in humans, pigs, and rabbits followed the one-site binding model of the Michaelis-Menten equation, while cattle and sheep followed the two-sites binding model of the Michaelis-Menten equation. Third, besides SEN, other hepatotoxic PAs including monocrotaline, adonifoline, and isoline also underwent N-glucuronidation in humans and several animal species such as rabbits, cattle, sheep, and pigs.

  3. Determining the degradation efficiency and mechanisms of ethyl violet using HPLC-PDA-ESI-MS and GC-MS

    Directory of Open Access Journals (Sweden)

    Chung Wen-Hsin

    2012-06-01

    Full Text Available Abstract Background The discharge of wastewater that contains high concentrations of reactive dyes is a well-known problem associated with dyestuff activities. In recent years, semiconductor photocatalysis has become more and more attractive and important since it has a great potential to contribute to such environmental problems. One of the most important aspects of environmental photocatalysis is in the selection of semiconductor materials like ZnO and TiO2, which are close to being two of the ideal photocatalysts in several respects. For example, they are relatively inexpensive, and they provide photo-generated holes with high oxidizing power due to their wide band gap energy. In this work, nanostructural ZnO film on the Zn foil of the Alkaline-Manganese Dioxide-Zinc Cell was fabricated to degrade EV dye. The major innovation of this paper is to obtain the degradation mechanism of ethyl violet dyes resulting from the HPLC-PDA-ESI-MS analyses. Results The fabrication of ZnO nanostructures on zinc foils with a simple solution-based corrosion strategy and the synthesis, characterization, application, and implication of Zn would be reported in this study. Other objectives of this research are to identify the reaction intermediates and to understand the detailed degradation mechanism of EV dye, as model compound of triphenylmethane dye, with active Zn metal, by HPLC-ESI-MS and GC-MS. Conclusions ZnO nanostructure/Zn-foils had an excellent potential for future applications on the photocatalytic degradation of the organic dye in the environmental remediation. The intermediates of the degradation process were separated and characterized by the HPLC-PDA-ESI-MS and GC-MS, and twenty-six intermediates were characterized in this study. Based on the variation of the amount of intermediates, possible degradation pathways for the decolorization of dyes are also proposed and discussed.

  4. Simultaneous determination of esculetin, quercetin-3-O-β-D-glucuronide, quercetin-3-O-β -D-glucuronopyranside methyl ester and quercetin in effective part of Polygonum Perfoliatum L. using high performace liquid chromatography

    Science.gov (United States)

    Fan, Dongsheng; Zhao, Yang; Zhou, Xin; Gong, Xiaojian; Zhao, Chao

    2014-01-01

    Objective: In the present study, a high performance liquid chromatography (HPLC) coupled with photodiode array detection was developed for simultaneous quantitation of esculetin, quercetin-3-O-β-D-glucuronide, quercetin-3-O-β-D- glucuronopyranoside methyl ester and quercetin in Polygonum perfoliatum L. Materials and Methods: The chromatographic separations were performed on a reversed-phase C18 column using a mobile phase composed of acetonitrile -0.5% aqueous acetic acid with gradient elution. The calibration curves for the analytes demonstrated good linearities within the investigated ranges. The satisfactory intra- and inter-day precision, repeatability and stability of the developed analytical method were shown in the method validation procedure. The recoveries of the established method ranged from 95.76 to 102.10% for all the analytes. Results: This proposed method was successfully applied for simultaneous quantification of the four compounds in effective part of Polygonum perfoliatum L. from different regions. Hierarchical clustering analysis (HCA) and principal components analysis (PCA) were performed to characterize and classify the samples based on the contents of the four compounds in Polygonum perfoliatum L. Conclusion: The established HPLC method combined with chemometric approaches was proven to be useful and efficient for quality control of Polygonum perfoliatum L. PMID:25210326

  5. Identification of sulfur interferences during organotin determination in harbour sediment samples by sodium tetraethyl borate ethylation and gas chromatography-pulsed flame photometric detection.

    Science.gov (United States)

    Bravo, Manuel; Lespes, Gäetane; De Gregori, Ida; Pinochet, Hugo; Potin-Gautier, Martine

    2004-08-13

    Because of the high toxicity of organotin compounds and the current regulation about their applications, analytical method usable in routine analysis is required. A speciation procedure based on NaBEt4 ethylation and GC-PFPD analysis has shown to be suitable for the organotin determination. Unfortunately, some matrix effects were observed during the analysis of harbour sediments from Chile. These effects were identified as the alkylation of elemental sulfur and the coelution between the organotin compounds and some dialkylsulfides. The re-optimization of GC parameters and application of solid phase microextraction (SPME) were proposed to solve these analytical problems. Certified reference materials and different harbour sediment samples were analysed in order to evaluate the suitability of the methods for organotin control in complex environment samples.

  6. UFLC-MS/MS method for simultaneous determination of luteolin-7-O-gentiobioside, luteolin-7-O-β-D-glucoside and luteolin-7-O-β-D-glucuronide in beagle dog plasma and its application to a pharmacokinetic study after administration of traditional Chinese medicinal preparation: Kudiezi injection.

    Science.gov (United States)

    Yin, Ran; Han, Fei; Tang, Zheng; Liu, Ran; Zhao, Xu; Chen, Xiaohui; Bi, Kaishun

    2013-01-01

    A rapid, sensitive and selective ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method for the simultaneous determination of three active flavonoid glycosides: luteolin-7-O-gentiobioside, luteolin-7-O-β-D-glucoside and luteolin-7-O-β-D-glucuronide in beagle dog plasma was developed and validated. Puerarin was used as internal standard (IS). After protein precipitation with acidified acetonitrile, the analytes were separated on a Venusil MP C18 column with a gradient elution system composed of 0.05% formic acid and acetonitrile at a flow rate of 0.4ml/min. Detection was performed using multiple reaction monitoring (MRM) mode with a turbo ion spray source under a negative ionization condition. The calibration curves of the three analytes showed good linearity (r>0.995) within the tested concentration ranges. The lower limits of quantification for luteolin-7-O-gentiobioside, luteolin-7-O-β-D-glucoside and luteolin-7-O-β-D-glucuronide were 1.0 ng/ml, 1.0 ng/ml and 4.0 ng/ml, respectively. The intra-day and inter-day precision and accuracy deviations were less than 15%, and the extraction recoveries of the three analytes from beagle dog plasma were more than 75%. The validated method was successfully applied to a pharmacokinetic study of the three flavonoid glycosides in beagle dog plasma after intravenous administration of the traditional Chinese medicinal preparation: Kudiezi injection. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Simultaneous determination of ethyl carbamate and 4-(5-)methylimidazole in yellow rice wine and soy sauce by gas chromatography with mass spectrometry.

    Science.gov (United States)

    Wu, Pinggu; Zhang, Liqun; Wang, Liyuan; Zhang, Jing; Tan, Ying; Tang, Jun; Ma, Bingjie; Pan, Xiaodong; Jiang, Wei

    2014-08-01

    We developed a new method, based on alkaline diatomite solid-phase extraction followed by gas chromatography with mass spectrometry, for the simultaneous determination of the toxic contaminants ethyl carbamate (EC) and 4-(5-)methylimidazole (4-MEI) in yellow rice wine and soy sauce. The optimal extraction conditions were defined. With the application of alkaline diatomite solid-phase extraction, damage to the capillary column by organic acids was greatly reduced. With deuterated EC used as the internal standard, the linearity of the calibration curves for EC and 4-MEI was good with correlation coefficient above 0.99. In a spiked experiment with EC and 4-MEI in yellow rice wine and soy sauce, recovery of the added EC was 80.5-102.5% and that of 4-MEI was 78.3-92.8%. The limit of quantification and limit of detection for EC were 6.0 and 2.0 μg/kg, respectively, and for 4-MEI were 15.0 and 5.0 μg/kg, respectively. The validation results demonstrate that the method is fast, simple, and selective, and therefore is suitable for simultaneously determining the presence of EC and 4-MEI in fermented food. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. PRACTICAL PREPARATION OF RESVERATROL 3-O-β-D-GLUCURONIDE

    OpenAIRE

    Jungong, Christian S.; Novikov, Alexei V.

    2012-01-01

    A practical synthesis of resveratrol 3-O-β-D-glucuronide, suitable for preparation of large quantities, was developed using selective deacetylation of resveratrol triacetate with ammonium acetate. A simplified procedure for large scale preparation of resveratrol is also reported.

  9. Hepatic UDP-glucuronosyltransferase is responsible for eslicarbazepine glucuronidation.

    Science.gov (United States)

    Loureiro, Ana I; Fernandes-Lopes, Carlos; Bonifácio, Maria J; Wright, Lyndon C; Soares-da-Silva, Patricio

    2011-09-01

    Eslicarbazepine acetate (ESL) is a once-daily novel antiepileptic drug approved in Europe for use as adjunctive therapy for refractory partial-onset seizures with or without secondary generalization. Metabolism of ESL consists primarily of hydrolysis to eslicarbazepine, which is then subject to glucuronidation followed by renal excretion. In this study, we have identified that human liver microsomes (HLM) enriched with uridine 5'-diphosphoglucuronic acid give origin to a single Escherichia coli β-glucuronidase-sensitive eslicarbazepine glucuronide (most likely the O-glucuronide). The kinetics of eslicarbazepine glucuronidation in HLM was investigated in the presence and absence of bovine serum albumin (BSA). The apparent K(m) were 412.2 ± 63.8 and 349.7 ± 74.3 μM in the presence and absence of BSA, respectively. Incubations with recombinant human UDP glucuronosyltransferases (UGTs) indicated that UGT1A4, UGT1A9, UGT2B4, UGT2B7, and UGT2B17 appear to be involved in eslicarbazepine conjugation. The UGT with the highest affinity for conjugation was UGT2B4 (K(m) = 157.0 ± 31.2 and 28.7 ± 10.1 μM, in the absence and presence of BSA, respectively). There was a significant correlation between eslicarbazepine glucuronidation and trifluoperazine glucuronidation, a typical UGT1A4 substrate; however, no correlation was found with typical substrates for UGT1A1 and UGT1A9. Diclofenac inhibited eslicarbazepine glucuronidation in HLM with an IC(50) value of 17 μM. In conclusion, glucuronidation of eslicarbazepine results from the contribution of UGT1A4, UGT1A9, UGT2B4, UGT2B7, and UGT2B17, but the high-affinity component of the UGT2B4 isozyme may play a major role at therapeutic plasma concentrations of unbound eslicarbazepine.

  10. Determination of phenolic profile by HPLC-ESI-MS/MS and anti-inflammatory activity of crude hydroalcoholic extract and ethyl acetate fraction from leaves of Eugenia brasiliensis

    Directory of Open Access Journals (Sweden)

    Diogo A. Siebert

    Full Text Available ABSTRACT Eugenia brasiliensis Lam., Myrtaceae, is used in folk medicine for anti-inflammatory diseases such as arthritis and rheumatism. This study investigated the anti-inflammatory activity and phenolic profile of the crude hydroalcoholic extract and ethyl acetate fraction from E. brasiliensis leaves. Crude hydroalcoholic extract and the ethyl acetate fraction were analyzed by HPLC-ESI-MS/MS in comparison to standard phenolic compounds. The anti-inflammatory activity of the crude hydroalcoholic extract (1, 10 and 25 mg kg-1 and the ethyl acetate fraction (10, 25 and 50 mg kg-1 was evaluated in a swiss mouse model of acute pleurisy induced by carrageenan, being the total cell count, exudation and analysis of nitrite/nitrate the inflammation parameters. HPLC-ESI-MS/MS analysis revealed apigenin, catechin, galangin, isoquercetin, myricetin, quercetin and rutin. Crude hydroalcoholic extract and ethyl acetate fraction were effective in inhibiting cell migration in all tested doses. Crude hydroalcoholic extract was effective in inhibiting exudation only at the 10 mg kg-1 dose; ethyl acetate fraction was effective in all tested doses. Results for nitrite/nitrate levels reveals that only the ethyl acetate fraction was effective at the tested doses. This is the first report of the presence of isoquercetin, galangin and apigenin in this species. Results from the phytochemical analysis enhance the chemical knowledge of this species. In the future, together with more studies, validation of its popular use in inflammatory diseases is possible.

  11. Simultaneous determination of ethyl carbamate and urea in Korean rice wine by ultra-performance liquid chromatography coupled with mass spectrometric detection.

    Science.gov (United States)

    Lee, Gyeong-Hweon; Bang, Dae-Young; Lim, Jung-Hoon; Yoon, Seok-Min; Yea, Myeong-Jai; Chi, Young-Min

    2017-10-15

    In this study, a rapid method for simultaneous detection of ethyl carbamate (EC) and urea in Korean rice wine was developed. To achieve quantitative analysis of EC and urea, the conditions for Ultra-performance liquid chromatography (UPLC) separation and atmospheric-pressure chemical ionization tandem mass spectrometry (APCI-MS/MS) detection were first optimized. Under the established conditions, the detection limit, relative standard deviation and linear range were 2.83μg/L, 3.75-5.96%, and 0.01-10.0mg/L, respectively, for urea; the corresponding values were 0.17μg/L, 1.06-4.01%, and 1.0-50.0μg/L, respectively, for EC. The correlation between the contents of EC and its precursor urea was determined under specific pH (3.5 and 4.5) and temperature (4, 25, and 50°C) conditions using the developed method. As a result, EC content was increased with greater temperature and lower pH. In Korean rice wine, urea was detected 0.19-1.37mg/L and EC was detected 2.0-7.7μg/L. The method developed in this study, which has the advantages of simplified sample preparation, low detection limits, and good selectivity, was successfully applied for the rapid analysis of EC and urea. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. New spectrophotometric method for determining nitrogen dioxide in air using 2,2-azino-bis(3-ethyl benzothiazoline)-6-sulfonic acid-diammonium salt and passive sampling.

    Science.gov (United States)

    Salem, Alaa A; Soliman, Ahmed A; El-Haty, Ismail A

    2011-01-01

    A new simple and highly sensitive spectrophotometric method for determining nitrogen dioxide in air was developed. The method is based on converting atmospheric nitrogen dioxide to nitrite ions within the IVL passive samplers used for samples collection. Acidifying nitrite ions with concentrated HCl produced the peroxynitrous acid oxidizing agent which was measured using 2, 2-azino-bis(3-ethyl benzothiazoline)-6-sulfonic acid-diammonium salt (ABTS) as reducing coloring agent. A parallel series of collected samples were measured for its nitrite content using a validated ion chromatographic method.The results obtained using both methods were compared in terms of their sensitivity and accuracy. Developed spectrophotometric method was shown to be one order of magnitude higher in sensitivity compared to the ion chromatographic method. Quantitation limits of 0.05 ppm and 0.55 μg/m(3) were obtained for nitrite ion and nitrogen dioxid, respectively. Standard deviations in the ranges of 0.05-0.59 and 0.63-7.92 with averages of 0.27 and 3.11 were obtained for determining nitrite and nitrogen dioxide, respectively.Student-t test revealed t-values less than 6.93 and 4.40 for nitrite ions and nitrogen dioxide, respectively. These values indicated insignificant difference between the averages of the newly developed method and the values obtained by ion chromatography at 95% confidence level.Compared to continuous monitoring techniques, the newly developed method has shown simple, accurate, sensitive, inexpensive and reliable for long term monitoring of nitrogen dioxide in ambient air.

  13. In Vitro Glucuronidation of Ochratoxin A by Rat Liver Microsomes

    Directory of Open Access Journals (Sweden)

    Zheng Han

    2013-12-01

    Full Text Available Ochratoxin A (OTA, one of the most toxic mycotoxins, can contaminate a wide range of food and feedstuff. To date, the data on its conjugates via glucuronidation request clarification and consolidation. In the present study, the combined approaches of ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS, UHPLC-Orbitrap-high resolution mass spectrometry (HRMS and liquid chromatography-multiple stage mass spectrometry (LC-MSn were utilized to investigate the metabolic profile of OTA in rat liver microsomes. Three conjugated products of OTA corresponding to amino-, phenol- and acyl-glucuronides were identified, and the related structures were confirmed by hydrolysis with β-glucuronidase. Moreover, OTA methyl ester, OTα and OTα-glucuronide were also found in the reaction solution. Based on these results, an in vitro metabolic pathway of OTA has been proposed for the first time.

  14. Simultaneous determination of myristyl nicotinate, nicotinic acid, and nicotinamide in rabbit plasma by liquid chromatography-tandem mass spectrometry using methyl ethyl ketone as a deproteinization solvent.

    Science.gov (United States)

    Catz, Paul; Shinn, Walter; Kapetanovic, Izet M; Kim, Hyuntae; Kim, Moonsun; Jacobson, Elaine L; Jacobson, Myron K; Green, Carol E

    2005-12-27

    Myristyl nicotinate (Nia-114) is an ester prodrug being developed for delivery of nicotinic acid (NIC) into the skin for prevention of actinic keratosis and its progression to skin cancer. To facilitate dermal studies of Nia-114, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using methyl ethyl ketone (MEK) as a deproteinization solvent was developed and validated for the simultaneous determination of Nia-114, NIC, and nicotinamide (NAM) in rabbit plasma. NAM is the principal metabolite of NIC, which is also expected to have chemopreventive properties. The analytes were chromatographically separated using a Spherisorb Cyano column under isocratic conditions, and detected by multiple reaction monitoring (MRM) in positive-ion electrospray ionization mode with a run time of 9 min. The method utilized a plasma sample volume of 0.2 ml and isotope-labeled D4 forms of each analyte as internal standards. The method was linear over the concentration range of 2-1000, 8-1000, and 75-1000 ng/ml, for Nia-114, NIC, and NAM, respectively. The intra- and inter-day assay accuracy and precision were within +/-15% for all analytes at low, medium, and high quality control standard levels. The relatively high value for the lower limit of quantitation (LLOQ) of NAM was demonstrated to be due to the high level of endogenous NAM in the rabbit plasma (about 350 ng/ml). Endogenous levels of NIC and NAM in human, dog, rat, and mouse plasma were also determined, and mean values ranged from NIC and 38.3 ng/ml NAM in human, to 233 ng/ml NIC and 622 ng/ml NAM in mouse. Nia-114 was generally unstable in rabbit plasma, as evidenced by loss of 44-50% at room temperature by 2 h, and loss of 64-70% upon storage at -20 degrees C for 1 week, whereas it was stable (<7% loss) upon storage at -80 degrees C for 1 month.

  15. Post-mortem levels and tissue distribution of codeine, codeine-6-glucuronide, norcodeine, morphine and morphine glucuronides in a series of codeine-related deaths.

    Science.gov (United States)

    Frost, Joachim; Løkken, Trine Nordgård; Helland, Arne; Nordrum, Ivar Skjåk; Slørdal, Lars

    2016-05-01

    This article presents levels and tissue distribution of codeine, codeine-6-glucuronide (C6G), norcodeine, morphine and the morphine metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in post-mortem blood (peripheral and heart blood), vitreous fluid, muscle, fat and brain tissue in a series of 23 codeine-related fatalities. CYP2D6 genotype is also determined and taken into account. Quantification of codeine, C6G, norcodeine, morphine, M3G and M6G was performed with a validated solid phase extraction LC-MS method. The series comprise 19 deaths (83%) attributed to mixed drug intoxication, 4 deaths (17%) attributed to other causes of death, and no cases of unambiguous monointoxication with codeine. The typical peripheral blood concentration pattern in individual cases was C6G≫codeine≫norcodeine>morphine, and M3G>M6G>morphine. In matrices other than blood, the concentration pattern was similar, although in a less systematic fashion. Measured concentrations were generally lower in matrices other than blood, especially in brain and fat, and in particular for the glucuronides (C6G, M3G and M6G) and, to some extent, morphine. In brain tissue, the presumed active moieties morphine and M6G were both below the LLOQ (0.0080mg/L and 0.058mg/L, respectively) in a majority of cases. In general, there was a large variability in both measured concentrations and calculated blood/tissue concentration ratios. There was also a large variability in calculated ratios of morphine to codeine, C6G to codeine and norcodeine to codeine in all matrices, and CYP2D6 genotype was not a reliable predictor of these ratios. The different blood/tissue concentration ratios showed no systematic relationship with the post-mortem interval. No coherent degradation or formation patterns for codeine, morphine, M3G and M6G were observed upon reanalysis in peripheral blood after storage. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. A rapid and specific derivatization procedure to identify acyl-glucuronides by mass spectrometry.

    Science.gov (United States)

    Vaz, Alfin D N; Wang, Wei Wei; Bessire, Andrew J; Sharma, Raman; Hagen, Anne E

    2010-07-30

    A simple procedure is described to identify acyl-glucuronides by coupled liquid chromatography/mass spectrometry after derivatization to a hydroxamic acid with hydroxylamine. The reaction specificity obviates the need for isolation of the acyl-glucuronide from an extract. Glucuronides derived from carbamic acids, and alkyl- and aromatic amines, are inert to the derivatization reaction conditions, making the hydroxamic acid derivative a fingerprint for acyl-glucuronides. Copyright 2010 John Wiley & Sons, Ltd.

  17. The Uptake by Plants of Diethylstilboestrol and of Its Glucuronide

    DEFF Research Database (Denmark)

    Gregers Hansen, B.

    1964-01-01

    The uptake of diethylstilboestrol and its glucuronide by plants could, under certain circumstances, present a potential health hazard. The relative uptake of the two compounds has therefore been studied in rye grass, red clover, mushrooms, and maize in pot and water culture experiments. It is con......The uptake of diethylstilboestrol and its glucuronide by plants could, under certain circumstances, present a potential health hazard. The relative uptake of the two compounds has therefore been studied in rye grass, red clover, mushrooms, and maize in pot and water culture experiments...

  18. Diethylstilbestrol can effectively accelerate estradiol-17-O-glucuronidation, while potently inhibiting estradiol-3-O-glucuronidation

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Liangliang; Xiao, Ling [The Centre for Drug and Food Safety Evaluation, School of Life Science, Anqing Normal University, Anqing 246011 (China); Xia, Yangliu [Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 (China); Zhou, Kun [College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600 (China); Wang, Huili; Huang, Minyi [The Centre for Drug and Food Safety Evaluation, School of Life Science, Anqing Normal University, Anqing 246011 (China); Ge, Guangbo, E-mail: geguangbo@dicp.ac.cn [Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 (China); Wu, Yan; Wu, Ganlin [The Centre for Drug and Food Safety Evaluation, School of Life Science, Anqing Normal University, Anqing 246011 (China); Yang, Ling, E-mail: yling@dicp.ac.cn [Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 (China)

    2015-03-01

    This in vitro study investigates the effects of diethylstilbestrol (DES), a widely used toxic synthetic estrogen, on estradiol-3- and 17-O- (E2-3/17-O) glucuronidation, via culturing human liver microsomes (HLMs) or recombinant UDP-glucuronosyltransferases (UGTs) with DES and E2. DES can potently inhibit E2-3-O-glucuronidation in HLM, a probe reaction for UGT1A1. Kinetic assays indicate that the inhibition follows a competitive inhibition mechanism, with the Ki value of 2.1 ± 0.3 μM, which is less than the possible in vivo level. In contrast to the inhibition on E2-3-O-glucuronidation, the acceleration is observed on E2-17-O-glucuronidation in HLM, in which cholestatic E2-17-O-glucuronide is generated. In the presence of DES (0–6.25 μM), K{sub m} values for E2-17-O-glucuronidation are located in the range of 7.2–7.4 μM, while V{sub max} values range from 0.38 to 1.54 nmol/min/mg. The mechanism behind the activation in HLM is further demonstrated by the fact that DES can efficiently elevate the activity of UGT1A4 in catalyzing E2-17-O-glucuronidation. The presence of DES (2 μM) can elevate V{sub max} from 0.016 to 0.81 nmol/min/mg, while lifting K{sub m} in a much lesser extent from 4.4 to 11 μM. Activation of E2-17-O-glucuronidation is well described by a two binding site model, with K{sub A}, α, and β values of 0.077 ± 0.18 μM, 3.3 ± 1.1 and 104 ± 56, respectively. However, diverse effects of DES towards E2-3/17-O-glucuronidation are not observed in liver microsomes from several common experimental animals. In summary, this study issues new potential toxic mechanisms for DES: potently inhibiting the activity of UGT1A1 and powerfully accelerating the formation of cholestatic E2-17-O-glucuronide by UGT1A4. - Highlights: • E2-3-O-glucuronidation in HLM is inhibited when co-incubated with DES. • E2-17-O-glucuronidation in HLM is stimulated when co-incubated with DES. • Acceleration of E2-17-O-glucuronidationin in HLM by DES is via activating the

  19. Quantitation of Buprenorphine, Norbuprenorphine, Buprenorphine Glucuronide, Norbuprenorphine Glucuronide, and Naloxone in Urine by LC-MS/MS.

    Science.gov (United States)

    Marin, Stephanie J; McMillin, Gwendolyn A

    2016-01-01

    Buprenorphine is an opioid drug that has been used to treat opioid dependence on an outpatient basis, and is also prescribed for managing moderate to severe pain. Some formulations of buprenorphine also contain naloxone to discourage misuse. The major metabolite of buprenorphine is norbuprenorphine. Both compounds are pharmacologically active and both are extensively metabolized to their glucuronide conjugates, which are also active metabolites. Direct quantitation of the glucuronide conjugates in conjunction with free buprenorphine, norbuprenorphine, and naloxone in urine can distinguish compliance with prescribed therapy from specimen adulteration intended to mimic compliance with prescribed buprenorphine. This chapter quantitates buprenorphine, norbuprenorphine, their glucuronide conjugates and naloxone directly in urine by liquid chromatography tandem mass spectrometry (LC-MS/MS). Urine is pretreated with formic acid and undergoes solid phase extraction (SPE) prior to analysis by LC-MS/MS.

  20. Synthesis, isolation and identification of glucuronides and mercapturic acids of a novel antiparasitic agent, licochalcone A

    DEFF Research Database (Denmark)

    Nadelmann, L.; Tjornelund, J.; Hansen, S. H.

    1997-01-01

    1. Four glucuronic acid conjugates of licochalcone A (Lica), and their metabolites, have been synthesized using rabbit and pig liver microsomes and purified by preparative hplc. 2. The glucuronides were identified as E-Lica 4'-O-beta-glucuronide, E and Z-Lica 4-O-beta-glucuronide and a mono-glucu...

  1. A novel method for the quantitation of gingerol glucuronides in human plasma or urine based on stable isotope dilution assays.

    Science.gov (United States)

    Schoenknecht, Carola; Andersen, Gaby; Schieberle, Peter

    2016-11-15

    The bio-active compounds of ginger (Zingiber officinale Roscoe), the gingerols, are gaining considerable attention due to their numerous beneficial health effects. In order to elucidate the physiological relevance of the ascribed effects their bioavailability has to be determined taking their metabolization into account. To quantitate in vivo generated [6]-, [8]- and [10]-gingerol glucuronides in human plasma and urine after ginger tea consumption, a simultaneous and direct liquid chromatography-tandem mass spectrometry method based on stable isotope dilution assays was established and validated. The respective references as well as the isotopically labeled substances were synthesized and characterized by mass spectrometry and NMR. Selective isolation of gingerol glucuronides from human plasma and urine by a mixed-phase anion-exchange SPE method led to recovery rates between 80.8 and 98.2%. LC-MS/MS analyses in selected reaction monitoring modus enabled a highly sensitive quantitation of gingerol glucuronides with LoQs between 3.9-9.8nmol/L in plasma and 39.3-161.1nmol/L in urine. The method precision in plasma and urine varied in the range±15%, whereas the intra-day accuracy in plasma and urine showed values between 78 and 122%. The developed method was then applied to a pilot study in which two volunteers consumed one liter ginger tea. Pharmacokinetic parameters like the maximum concentration (cmax), the time to reach cmax (tmax), area under the curve (AUC), elimination rate constant (kel) and elimination half-life (t1/2) were calculated from the concentration-time curve of each gingerol glucuronide. The obtained results will enable more detailed investigation of gingerol glucuronides as bioactives in their physiologically relevant concentrations. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Simultaneous preparation of α/β-zearalenol glucosides and glucuronides.

    Science.gov (United States)

    Mikula, Hannes; Weber, Julia; Lexmüller, Stefan; Bichl, Gerlinde; Schwartz, Heidi; Varga, Elisabeth; Berthiller, Franz; Hametner, Christian; Krska, Rudolf; Fröhlich, Johannes

    2013-05-24

    An improved and reproducible procedure for the preparation of four different glycosides of the mycotoxins α- and β-zearalenol (α,β-ZEL), both metabolites of the Fusarium toxin zearalenone (ZEN), is reported. These conjugated or masked mycotoxins are formed during phase II metabolism in plants (glucosides) or animals and humans (glucuronides). Improved regioselective Königs-Knorr glucuronidation was applied to ZEN followed by reduction of the keto group of the mycotoxin, leading to α- and β-configuration of ZEL and also to a partial reduction of the glucuronic acid methyl ester to obtain the corresponding glucosides. After deprotection of the sugar moiety, α- and β-zearalenol-14-β,D-glucuronide as well as the corresponding glucosides were isolated at once using preparative HPLC. The reduction step was studied under different reaction conditions to finally develop an optimized and also tunable procedure for the first simultaneous preparation of both, glucosides and glucuronides of a xenobiotic substance in reasonable amounts to be used as reference materials for bioanalytical and toxicological investigations. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Isoflavones modulate the glucuronidation of estradiol in human liver microsomes

    National Research Council Canada - National Science Library

    Pfeiffer, Erika; Treiling, Christian R; Hoehle, Simone I; Metzler, Manfred

    2005-01-01

    ... by the endogenous hormone 17beta-estradiol (E2). In the present study, we have examined if daidzein and genistein as well as several structurally related isoflavones are able to modulate the in vitro glucuronidation of E2 in human hepatic microsomes...

  4. Stereoselective disposition and glucuronidation of propranolol in humans.

    Science.gov (United States)

    Silber, B; Holford, N H; Riegelman, S

    1982-06-01

    Following oral dosing to steady state, the disposition of S(-)- and R(+)-propranolol and their corresponding glucuronide conjugates was studied in 4 healthy adults using doses from 40 to 320 mg/day of the racemate. Steady -state plasma concentrations of S(-)-propranolol and its corresponding glucuronide conjugate were greater than that for R(+)-propranolol and its corresponding conjugate. The average steady-state concentration of both enantiomers increased disproportionately to dose. There was a 52+/- 7 (mean +/- SD) % decrease in the intrinsic clearance (clint) of S(-)-propranolol and a 65 +/- 22% decrease in the Clint of R(+)-propranolol over the dosing range studied. The terminal elimination half-lives of S(-)-propranolol and its glucuronide conjugate were longer than for the R(+)-enantiomer at all doses. The formation of glucuzonide conjugates of S(-)- and R(+)-propranolol was best described by a saturable process in all subjects. Within individuals, the ratio of Vmax/Km for the glucuronide conjugate of S(-)-propranolol was from 2.1-to 4.9-fold greater than for the conjugate of the R(+)-enantiomer. These studies demonstrate for the first time, that propranolol undergoes stereoselective disposition in humans.

  5. Cyp3a11-mediated testosterone-6β-hydroxylation decreased, while UGT1a9-mediated propofol O-glucuronidation increased, in mice with diabetes mellitus.

    Science.gov (United States)

    Shi, Rong; Wu, Jiasheng; Meng, Cong; Ma, Bingliang; Wang, Tianming; Li, Yuanyuan; Ma, Yueming

    2016-10-01

    The db/db mouse is one of the most popular animal models for type 2 diabetes mellitus, but changes in the activities of important P450s and UGTs are still not completely clear. This study was designed to investigate the alterations of major hepatic cytochrome P450s and UDP-glucuronyltransferase enzymes in db/db mice. Mouse liver microsomes (MLMs) were obtained from male db/db mice and their wild type littermates. After incubation of the substrates separately with MLMs, the samples were pooled and analysed by high-throughput liquid chromatography-tandem mass spectrometry system for the simultaneous study of nine phase I metabolic reactions and three glucuronidation conjugation reactions to determine the activity of the metabolic enzymes. Compared with normal controls, the Cl int estimate for testosterone-6β-hydroxylation was lower (46%) (p coumarin-7-hydroxylation, bupropion-hydroxylation, omeprazole-5-hydroxylation, dextromethorphan-O-demethylation, tolbutamide-4-hydroxylation, chlorzoxazone-6-hydroxylation and midazolam-1-hydroxylation and in glucuronidation reactions of estradiol 3-O-glucuronidation, and 3-azido-3-deoxythymidine glucuronidation. The data suggest that, in db/db mice, the activity of Cyp3a11, catalysing testosterone-6β-hydroxylation, decreased, while the activity of UGT1a9, catalysing propofol O-glucuronidation, increased. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  6. Hepatic synthesis and urinary elimination of acetaminophen glucuronide are exacerbated in bile duct-ligated rats.

    Science.gov (United States)

    Villanueva, Silvina S M; Ruiz, María L; Ghanem, Carolina I; Luquita, Marcelo G; Catania, Viviana A; Mottino, Aldo D

    2008-03-01

    Renal and intestinal disposition of acetaminophen glucuronide (APAP-GLU), a common substrate for multidrug resistance-associated proteins 2 and 3 (Mrp2 and Mrp3), was assessed in bile duct-ligated rats (BDL) 7 days after surgery using an in vivo perfused jejunum model with simultaneous urine collection. Doses of 150 mg/kg b.w. (i.v.) or 1 g/kg b.w. (i.p.) of acetaminophen (APAP) were administered, and its glucuronide was determined in bile (only Shams), urine, and intestinal perfusate throughout a 150-min period. Intestinal excretion of APAP-GLU was unchanged or decreased (-58%) by BDL for the 150 mg and 1 g/kg b.w. doses of APAP, respectively. In contrast, renal excretion was increased by 200 and 320%, respectively. Western studies revealed decreased levels of apical Mrp2 in liver and jejunum but increased levels in renal cortex from BDL animals, whereas Mrp3 was substantially increased in liver and not affected in kidney or intestine. The global synthesis of APAP-GLU, determined as the sum of cumulative excretions, was higher in BDL rats (+51 and +110%) for these same doses of APAP as a consequence of a significant increase in functional liver mass, with no changes in specific glucuronidating activity. Expression of apical breast cancer resistance protein, which also transports nontoxic metabolites of APAP, was decreased by BDL in liver and renal cortex, suggesting a minor participation of this route. We demonstrate a more efficient hepatic synthesis and basolateral excretion of APAP-GLU followed by its urinary elimination in BDL group, the latter two processes consistent with up-regulation of liver Mrp3 and renal Mrp2.

  7. The Impact of Glucuronidation on the Bioactivation and DNA Adduction of the Cooked-Food Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b] pyridine in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Malfatti, M A; Ubick, E A; Felton, J S

    2005-03-31

    UDP-glucuronosyltransferases (UGTs) catalyze the glucuronidation of many different chemicals. Glucuronidation is especially important for detoxifying reactive intermediates from metabolic reactions, which otherwise can be biotransformed into highly reactive cytotoxic or carcinogenic species. Detoxification of certain food-borne carcinogenic heterocyclic amines (HAs) is highly dependent on UGT1A-mediated glucuronidation. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most mass abundant carcinogenic HA found in well-done cooked meat, is extensively glucuronidated by UGT1A proteins. In humans, CYP1A2 catalyzed N-hydroxylation and subsequent UGT1A-mediated glucuronidation is a dominant pathway in the metabolism of PhIP. Therefore, changes in glucuronidation rates could significantly alter PhIP metabolism. To determine the importance of UGT1A-mediated glucuronidation in the biotransformation of PhIP, UGT1A proficient Wistar and UGT1A deficient Gunn rats were exposed to a single 100 {micro}g/kg oral dose of [{sup 14}C]-PhIP. Urine was collected over 24 h and the PhIP urinary metabolite profiles were compared between the two strains. After the 24 h exposure, livers and colon were removed and analyzed for DNA adduct formation by accelerator mass spectrometry. Wistar rats produced several PhIP and N-hydroxy-PhIP glucuronides that accounted for {approx}25% of the total amount of recovered urinary metabolites. In the Gunn rats, PhIP and N-hydroxy-PhIP glucuronides were reduced by 68-92%, compared to the Wistar rats, and comprised only 4% of the total amount of recovered urinary metabolites. PhIP-DNA adduct analysis from the Gunn rats revealed a correlation between reduced PhIP and N-hydroxy-PhIP glucuronide levels in the urine and increased hepatic DNA adducts, compared to the Wistar rats. These results indicate that UGT1A-mediated glucuronidation of PhIP and N-hydroxy-PhIP is an important pathway for PhIP detoxification. Failure to form glucuronide conjugates

  8. Identification of flunixin glucuronide and depletion of flunixin and its marker residue in bovine milk.

    Science.gov (United States)

    Jedziniak, P; Olejnik, M; Szprengier-Juszkiewicz, T; Smulski, S; Kaczmarowski, M; Żmudzki, J

    2013-12-01

    Residues of flunixin [and its marker residue 5-hydroxyflunixin (5OHFLU)] were determined in milk from cows that intravenously received therapeutic doses of the drug. The samples were collected during each milking (every 12 h) for six consecutive days, and concentrations of flunixin and its metabolites were determined by the method with and without enzymatic hydrolysis (beta-glucuronidase). The highest flunixin concentration in milk was observed 12 h after dosing (2.4 ± 1.42 μg/kg, mean ± SD). Flunixin concentrations in the samples determined with enzymatic hydrolysis were significantly higher (P flunixin glucuronide to the milk. Additionally, unambiguous identification of flunixin glucuronide in the bovine milk was performed with linear ion-trap mass spectrometry. The 5OHFLU concentrations analyzed without enzymatic hydrolysis (22.3 ± 16.04 μg/kg) were similar to this obtained with enzymatic hydrolysis. Flunixin and 5OHFLU concentrations dropped below the limits of detection at 48 h after last dosing. © 2013 John Wiley & Sons Ltd.

  9. GLUCURONIDATION OF LABETALOL AT THE 2 HYDROXY POSITIONS BY BOVINE LIVER-MICROSOMES - ISOLATION, PURIFICATION, AND STRUCTURE ELUCIDATION OF THE GLUCURONIDES OF LABETALOL

    NARCIS (Netherlands)

    NIEMEIJER, NR; GERDING, TK; DEZEEUW, RA

    1991-01-01

    Glucuronidation is known to be a major metabolic pathway for labetalol. As the drug contains a phenolic and an alcoholic hydroxy group, in principle two regio isomeric glucuronides can be formed. By incubating the substrate labetalol with bovine liver microsomes, in the presence of the co-substrate

  10. Antimicrobial activity of ethyl acetate extract of Citrullus lanatus seeds

    African Journals Online (AJOL)

    Purpose: To determine the antimicrobial activity and chemical constituents of ethyl acetate extract of Citrullus lanatus seeds. Methods: Antimicrobial activity of the ethyl acetate extract of the seeds of C. lanatus was evaluated against Staphylococus aureus ATCC 25923, Escherichia coli ATCC 25922, Bacillus subtilis ...

  11. Human UDP-Glucuronosyltransferase 1A1 is the Primary Enzyme Responsible for the N-glucuronidation of N-hydroxy-PhIP in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Malfatti, M A; Felton, J S

    2004-04-06

    UDP-Glucuronosyltransferase 1A proteins (UGT1A) catalyze the glucuronidation of many endogenous and xenobiotic compounds including heterocyclic amines and their hydroxylated metabolites (the main topic of this study). Studies have shown that in humans UGT1A mediated glucuronidation is an important pathway in the detoxification of food-borne carcinogenic heterocyclic amines. The biotransformation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most mass abundant heterocyclic amine found in cooked meats, is highly dependent on cytochrome P4501A2 hydroxylation followed by UGT catalyzed glucuronidation of the N-hydroxy-PhIP reactive intermediate. To determine which UGT1A proteins are involved in the glucuronidation of N-hydroxy-PhIP, microsomal preparations from baculovirus infected insect cells that express all of the known functional human UGT1A isozymes (UGT1A1, -1A3, -1A4, -1A6, -1A7, -1A8, -1A9, -1A10) were exposed to N-hydroxy-PhIP and the reaction products were isolated by HPLC. All UGT1A proteins except UGT1A6 showed some degree of activity towards N-hydroxy-PhIP. The formation of both N-hydroxy-PhIP-N{sup 2}-glucuronide and N-hydroxy-PhIP-N3-glucuronide was both time and substrate concentration dependent in all the microsomal incubations that showed appreciable activity. UGT1A1 was the most efficient in converting N-hydroxy-PhIP to both conjugates producing 5 times more of the N{sup 2}-conjugate than UGT1A4, the next active UGT, and 286 times more than UGT1A7, the least active UGT. With an apparent Km of 52 {micro}M and a K{sub cat} of 114 min-1, UGT1A1 was also the most catalytically efficient in forming N-hydroxy-PhIP-N{sup 2}-glucuronide. Catalytic constants for UGT1A4, UGT1A8 and UGT1A9 were 52 min-1, 35 min{sup -1} and 3.7 min{sup -1}, respectively. The catalytic efficiency for N-hydroxy-PhIP-N3-glucuronide formation was 8, 10, and 6 times lower for UGT1A1, -1A4, and -1A8, respectively, when compared to the k{sub cat} values for N

  12. Breast cancer resistance protein (Bcrp1/Abcg2) limits net intestinal uptake of quercetin in rats by facilitating apical efflux of glucuronides

    NARCIS (Netherlands)

    Sesink, Aloys L. A.; Arts, Ilja C. W.; de Boer, Vincent C. J.; Breedveld, Pauline; Schellens, Jan H. M.; Hollman, Peter C. H.; Russel, Frans G. M.

    2005-01-01

    The intestinal absorption of the flavonoid quercetin in rats is limited by the secretion of glucuronidated metabolites back into the gut lumen. The objective of this study was to determine the role of the intestinal efflux transporters breast cancer resistance protein (Bcrp1)/Abcg2 and multidrug

  13. Breast cancer resistance protein (Bcrp1/Abcg2) limits net intestinal uptake of quercetin in rats by facilitating apical efflux of glucuronides.

    NARCIS (Netherlands)

    Sesink, A.L.; Arts, I.C.; Boer, V.C. de; Breedveld, P.; Schellens, J.H.M.; Hollman, P.C.H.; Russel, F.G.M.

    2005-01-01

    The intestinal absorption of the flavonoid quercetin in rats is limited by the secretion of glucuronidated metabolites back into the gut lumen. The objective of this study was to determine the role of the intestinal efflux transporters breast cancer resistance protein (Bcrp1)/Abcg2 and multidrug

  14. Hydroxycinnamic acid ethyl esters as precursors to ethylphenols in wine.

    Science.gov (United States)

    Hixson, Josh L; Sleep, Nicola R; Capone, Dimitra L; Elsey, Gordon M; Curtin, Christopher D; Sefton, Mark A; Taylor, Dennis K

    2012-03-07

    A method for determining ethyl coumarate and ethyl ferulate in wine using GC-MS with deuterium-labeled analogues has been developed and used to measure the evolution of these two esters during the production of two commercial monovarietal red wines, cv. Grenache and Shiraz. During fermentation, the concentration of ethyl coumarate rose from low levels to 0.4 mg/L in Grenache and 1.6 mg/L in Shiraz wines. These concentrations then increased further during barrel aging to 1.4 and 3.6 mg/L, respectively. The concentration of ethyl ferulate was much lower, reaching a maximum of only 0.09 mg/L. Conversion of ethyl coumarate and ethyl ferulate to their corresponding ethylphenols was observed during fermentations of a synthetic medium with two strains of Dekkera bruxellensis (AWRI 1499 and AWRI 1608), while a third (strain AWRI 1613) produced no ethylphenols at all from these precursors. Strains AWRI 1499 and 1608 produced 4-ethylphenol from ethyl coumarate in 68% and 57% yields, respectively. The corresponding yields of 4-ethylguaiacol from ethyl ferulate were much lower, 7% and 3%. Monitoring of ethyl coumarate and ethyl ferulate concentration during the Dekkera fermentations showed that the selectivity for ethylphenol production according to yeast strain and the precursor was principally a result of variation in esterase activity. Consequently, ethyl coumarate can be considered to be a significant precursor to 4-ethylphenol in wines affected by these two strains of Brettanomyces/Dekkera yeast, while ethyl ferulate is not an important precursor to 4-ethylguaiacol.

  15. Forensic confirmatory analysis of ethyl sulfate--a new marker for alcohol consumption--by liquid-chromatography/electrospray ionization/tandem mass spectrometry.

    Science.gov (United States)

    Dresen, Sebastian; Weinmann, Wolfgang; Wurst, Friedrich Martin

    2004-11-01

    Ethyl sulfate (EtS)--a new direct marker for ethanol intake besides ethyl glucuronide (EtG) and others--was detected in urine samples by electrospray ionization tandem mass-spectrometry (LC-ESI-MS/MS). Ethyl sulfate sodium salt was used for method development, yielding a precursor [M - H]- m/z 125 and product ions m/z 97 [HSO4]- and m/z 80 [SO3]-. Pentadeuterated EtS (D5-EtS) was synthesized by esterification of sulfuric acid with anhydrous hexadeutero ethanol ([M - H]- m/z 130, product ions m/z 98 [DSO4]- and m/z 80 [SO3]-). After addition of D5-EtS and D5-EtG, urine samples were analyzed by direct injection into the gradient LC-MS/MS system. Analysis was performed in accordance with forensic guidelines for confirmatory analysis using one precursor and two product ions. EtS has been detected (in addition to EtG) in the urine samples of nine volunteers after drinking sparkling wine containing between 9 and 49 g of ethanol. Both EtS and EtG could be detected up to 36 h after consumption of alcohol. The excretion profile was found to be similar to that of EtG. No EtS was found in teetotalers' urine samples. Method validation parameters are presented. EtS was stable in urine upon storage up to twenty days at room temperature. In addition to EtG, EtS can be used to detect recent alcohol consumption, thus providing a second marker for the time range of up to approximately one day after elimination of ethanol from urine samples. The determination of EtS can be used in addition to EtG as proof of ethanol consumption in workplace monitoring programs.

  16. The Inhibition of Hepatic and Renal Glucuronidation ofp-Nitrophenol and 4-Methylumbelliferone by Oil Palm Empty Fruit Bunch Lignin and Its Main Oxidation Compounds.

    Science.gov (United States)

    Salleh, Norliyana Mohamad; Ismail, Sabariah; Ibrahim, Mohamad Nasir Mohamad

    2017-01-01

    In order to develop oil palm empty fruit bunch (EFB) lignin as a nutraceutical and health supplement, the investigation of its potential in interacting with other drugs via inhibition of drug-metabolizing enzymes (DMEs) would ensure product safety. The study was aimed to investigate the in vitro effect of oil palm EFB lignin and its main oxidation compounds on phase II DME UDP-glucuronosyltransferases (UGTs) in rat liver and kidney microsomes. The p -nitrophenol ( p -NP) and 4-methylumbelliferone (4-MU) were employed as probe substrates in glucuronidation assays. The effect of soda oil palm EFB lignin on V max , K m , CL int , K i , and mode of inhibition of 4-MU glucuronidation in RLM was also determined. The inhibitory potency of oil palm EFB lignin for both p -NP and 4-MU glucuronidation in rat liver microsome (RLM) and rat kidneys microsomes (RKM) was found to be in the rank order of soda > kraft > organosolv. However, the inhibitory potency of its main oxidation compounds were in the rank order of vanillin > syringaldehyde > p -hydroxybenzaldehyde. Soda oil palm EFB lignin exhibited mixed-type inhibition against 4-MU glucuronidation in RLM, showing the change in apparent V max and with only a minor effect on K m compared with control. The findings showed that effect of oil palm EFB lignin on both p -NP and 4-MU glucuronidation in RLM and RKM was enhanced by the presence of vanillin as well as flavonoids. Kinetic study showed that soda oil palm EFB lignin exhibited strong inhibition on UGT activity in RLM with mixed-type inhibition mode. The inhibitory potential of oil palm EFB lignin extracts for p -NP and 4-MU glucuronidation in RLM and RKM can be listed in the following rank order: soda > kraft > organosolvThe inhibitory potential of oil palm EFB lignin main oxidation compounds for p -NP and 4-MU glucuronidation in RLM and RKM can be listed in the following rank order: vanillin > syringaldehyde > p-hydroxybenzaldehydeResults suggested that the effect of oil

  17. Determinação de carbamato de etila em aguardentes de cana por CG-EM Determination of ethyl carbamate in sugar cane spirits by GC-MS

    Directory of Open Access Journals (Sweden)

    Renata Adriana Labanca

    2008-01-01

    Full Text Available A simple, specific and sensitive GC-MS procedure with ion m/z 62 was validated for the determination of ethyl carbamate (EC in spirits. It exhibited linearity over the concentration of 30 to 600 μg/L with 30 μg/L limit of quantification. EC was detected in 70 of the 71 samples analyzed with levels from 33 to 2609 μg/L (mean level = 893 μg/L. 35% of the samples contained 500 to 1000 μg/L and 23% contained 150 to 500 and 1000 to 1500 μg/L. No significant correlation was found between EC and the levels of copper, pH and alcohol content of the samples.

  18. Deconjugation Kinetics of Glucuronidated Phase II Flavonoid Metabolites by B-glucuronidase from Neutrophils

    NARCIS (Netherlands)

    Bartholomé, R.; Haenen, G.; Hollman, P.C.H.; Bast, A.; Dagnelie, P.C.; Roos, D.; Keijer, J.; Kroon, P.A.; Needs, P.W.; Arts, I.C.W.

    2010-01-01

    Flavonoids are inactivated by phase II metabolism and occur in the body as glucuronides. Mammalian ß-glucuronidase released from neutrophils at inflammatory sites may be able to deconjugate and thus activate flavonoid glucuronides. We have studied deconjugation kinetics and pH optimum for four

  19. Deconjugation Kinetics of Glucuronidated Phase II Flavonoid Metabolites by beta-glucuronidase from Neutrophils

    NARCIS (Netherlands)

    Bartholomé, R.; Haenen, G.; Hollman, P.C.H.; Bast, A.; Dagnelie, P.C.; Roos, D.; Keijer, J.; Kroon, P.A.; Needs, P.W.; Arts, I.C.W.

    2010-01-01

    Flavonoids are inactivated by phase II metabolism and occur in the body as glucuronides. Mammalian beta-glucuronidase released from neutrophils at inflammatory sites may be able to deconjugate and thus activate flavonoid glucuronides. We have studied deconjugation kinetics and pH optimum for four

  20. Deconjugation kinetics of glucuronidated phase II flavonoid metabolites by beta-glucuronidase from neutrophils

    NARCIS (Netherlands)

    Bartholomé, Roger; Haenen, Guido; Hollman, C. H.; Bast, Aalt; Dagnelie, Pieter C.; Roos, Dirk; Keijer, Jaap; Kroon, Paul A.; Needs, Paul W.; Arts, Ilja C. W.

    2010-01-01

    Flavonoids are inactivated by phase II metabolism and occur in the body as glucuronides. Mammalian beta-glucuronidase released from neutrophils at inflammatory sites may be able to deconjugate and thus activate flavonoid glucuronides. We have studied deconjugation kinetics and pH optimum for four

  1. Use of urinary pregnanediol 3-glucuronide to confirm ovulation.

    Science.gov (United States)

    Ecochard, R; Leiva, R; Bouchard, T; Boehringer, H; Direito, A; Mariani, A; Fehring, R

    2013-10-01

    Urinary hormonal markers may assist in increasing the efficacy of Fertility Awareness Based Methods (FABM). This study uses urinary pregnanediol-3a-glucuronide (PDG) testing to more accurately identify the infertile phase of the menstrual cycle in the setting of FABM. Secondary analysis of an observational and simulation study, multicentre, European study. The study includes 107 women and tracks daily first morning urine (FMU), observed the changes in cervical mucus discharge, and ultrasonography to identify the day of ovulation over 326 menstrual cycles. The following three scenarios were tested: (A) use of the daily pregnandiol-3a-glucuronide (PDG) test alone; (B) use of the PDG test after the first positive urine luteinizing hormone (LH) kit result; (C) use of the PDG test after the disappearance of fertile type mucus. Two models were used: (1) one day of PDG positivity; or (2) waiting for three days of PDG positivity before declaring infertility. After the first positivity of a LH test or the end of fertile mucus, three consecutive days of PDG testing over a threshold of 5μg/mL resulted in a 100% specificity for ovulation confirmation. They were respectively associated an identification of an average of 6.1 and 7.6 recognized infertile days. The results demonstrate a clinical scenario with 100% specificity for ovulation confirmation and provide the theoretical background for a future development of a competitive lateral flow assay for the detection of PDG in the urine. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Species differences in drug glucuronidation: Humanized UDP-glucuronosyltransferase 1 mice and their application for predicting drug glucuronidation and drug-induced toxicity in humans.

    Science.gov (United States)

    Fujiwara, Ryoichi; Yoda, Emiko; Tukey, Robert H

    2017-10-07

    More than 20% of clinically used drugs are glucuronidated by a microsomal enzyme UDP-glucuronosyltransferase (UGT). Inhibition or induction of UGT can result in an increase or decrease in blood drug concentration. To avoid drug-drug interactions and adverse drug reactions in individuals, therefore, it is important to understand whether UGTs are involved in metabolism of drugs and drug candidates. While most of glucuronides are inactive metabolites, acyl-glucuronides that are formed from compounds with a carboxylic acid group can be highly toxic. Animals such as mice and rats are widely used to predict drug metabolism and drug-induced toxicity in humans. However, there are marked species differences in the expression and function of drug-metabolizing enzymes including UGTs. To overcome the species differences, mice in which certain drug-metabolizing enzymes are humanized have been recently developed. Humanized UGT1 (hUGT1) mice were created in 2010 by crossing Ugt1-null mice with human UGT1 transgenic mice in a C57BL/6 background. hUGT1 mice can be promising tools to predict human drug glucuronidation and acyl-glucuronide-associated toxicity. In this review article, studies of drug metabolism and toxicity in the hUGT1 mice are summarized. We further discuss research and strategic directions to advance the understanding of drug glucuronidation in humans. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  3. Ethyl methanesulfonate mutagenesis in Schizosaccharomyces pombe

    DEFF Research Database (Denmark)

    Ekwall, Karl; Thon, Genevieve

    2017-01-01

    Here we provide an ethyl methanesulfonate (EMS) mutagenesis protocol for Schizosaccharomyces pombe cells.......Here we provide an ethyl methanesulfonate (EMS) mutagenesis protocol for Schizosaccharomyces pombe cells....

  4. In vitro stability of free and glucuronidated cannabinoids in urine following controlled smoked cannabis.

    Science.gov (United States)

    Desrosiers, Nathalie A; Lee, Dayong; Scheidweiler, Karl B; Concheiro-Guisan, Marta; Gorelick, David A; Huestis, Marilyn A

    2014-01-01

    Analyte stability is an important factor in urine test interpretation, yet cannabinoid stability data are limited. A comprehensive study of Δ(9)-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol, cannabinol, THC-glucuronide, and THCCOOH-glucuronide stabilities in authentic urine was completed. Urine samples after ad libitum cannabis smoking were pooled to prepare low and high pools for each study participant; baseline concentrations were measured within 24 h at room temperature (RT), 4 °C and -20 °C. Stability at RT, 4 °C and -20 °C was evaluated by Friedman tests for up to 1 year. THCCOOH, THC-glucuronide, and THCCOOH-glucuronide were quantified in baseline pools. RT THCCOOH baseline concentrations were significantly higher than -20 °C, but not 4 °C baseline concentrations. After 1 week at RT, THCCOOH increased, THCCOOH-glucuronide decreased, but THC-glucuronide was unchanged. In RT low pool, total THCCOOH (THCCOOH + THCCOOH-glucuronide) was significantly lower after 1 week. At 4 °C, THCCOOH was stable 2 weeks, THCCOOH-glucuronide 1 month and THC-glucuronide for at least 6 months. THCCOOH was stable frozen for 1 year, but 6 months high pool results were significantly higher than baseline; THC-glucuronide and THCCOOH-glucuronide were stable for 6 months. Total THCCOOH was stable 6 months at 4 °C, and frozen 6 months (low) and 1 year (high). THC, cannabidiol and cannabinol were never detected in urine; although not detected initially, 11-OH-THC was detected in 2 low and 3 high pools after 1 week at RT. Substantial THCCOOH-glucuronide deconjugation was observed at RT and 4 °C. Analysis should be conducted within 3 months if non-hydrolyzed THCCOOH or THCCOOH-glucuronide quantification is required.

  5. Catalytic Combustion of Ethyl Acetate

    OpenAIRE

    ÖZÇELİK, Tuğba GÜRMEN; ATALAY, Süheyda; ALPAY, Erden

    2014-01-01

    The catalytic combustion of ethyl acetate over prepared metal oxide catalysts was investigated. CeO, Co2O3, Mn2O3, Cr2O3, and CeO-Co2O3 catalysts were prepared on monolith supports and they were tested. Before conducting the catalyst experiments, we searched for the homogeneous gas phase combustion reaction of ethyl acetate. According to the homogeneous phase experimental results, 45% of ethyl acetate was converted at the maximum reactor temperature tested (350 °C). All the prepare...

  6. Variation in trans-3'-hydroxycotinine glucuronidation does not alter the nicotine metabolite ratio or nicotine intake.

    Directory of Open Access Journals (Sweden)

    Andy Z X Zhu

    Full Text Available CYP2A6 metabolizes nicotine to its primary metabolite cotinine and also mediates the metabolism of cotinine to trans-3'-hydroxycotinine (3HC. The ratio of 3HC to cotinine (the "nicotine metabolite ratio", NMR is an in vivo marker for the rate of CYP2A6 mediated nicotine metabolism, and total nicotine clearance, and has been associated with differences in numerous smoking behaviors. The clearance of 3HC, which affects the NMR, occurs via renal excretion and metabolism by UGT2B17, and possibly UGT2B10, to 3HC-glucuronide. We investigated whether slower 3HC glucuronidation alters NMR, altering its ability to predict CYP2A6 activity and reducing its clinical utility.Plasma NMR, three urinary NMRs, three urinary 3HC glucuronidation phenotypes and total nicotine equivalents were examined in 540 African American smokers. The UGT2B17 gene deletion and UGT2B10*2 were genotyped.The UGT2B17 gene deletion, but not UGT2B10*2 genotype, was associated with slower 3HC glucuronidation (indicated by three 3HC-glucuronidation phenotypes, indicating its role in this glucuronidation pathway. However, neither lower rates of 3HC glucuronidation, nor the presence of a UGT2B17 and UGT2B10 reduced function allele, altered plasma or urinary NMRs or levels of smoking.Variation in 3HC glucuronidation activity, including these caused by UGT2B17 gene deletions, did not significantly alter NMR and is therefore unlikely to affect the clinical utility of NMR in smoking behavior and cessation studies. This study demonstrates that NMR is not altered by differences in the rate of 3HC glucuronidation, providing further support that NMR is a reliable indicator of CYP2A6 mediated nicotine metabolism.

  7. 21 CFR 173.228 - Ethyl acetate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethyl acetate. 173.228 Section 173.228 Food and..., Lubricants, Release Agents and Related Substances § 173.228 Ethyl acetate. Ethyl acetate (CAS Reg. No. 141-78... the specifications of the Food Chemicals Codex, 1 (Ethyl Acetate; p. 372, 3d Ed., 1981), which are...

  8. Toxicity Studies of Ethyl Maltol and Iron Complexes in Mice

    Directory of Open Access Journals (Sweden)

    Zhen Li

    2017-01-01

    Full Text Available Ethyl maltol and iron complexes are products of ethyl maltol and the iron found in the cooking pots used to prepare the Chinese dish, hot-pot. Because their safety is undocumented, the toxicity study of ethyl maltol and iron complexes was conducted in male and female Kunming (KM mice. The animal study was designed based on the preliminary study conducted to determine the median lethal dose (LD50. The doses used in the study were 0, 1/81, 1/27, 1/9, and 1/3 of the LD50 (mg kg body weight (BW−1 day−1 dissolved in the water. The oral LD50 of the ethyl maltol and iron complexes was determined to be 743.88 mg kg BW−1 in mice. The ethyl maltol and iron complexes targeted the endocrine organs including the liver and kidneys following the 90 D oral exposure. Based on the haematological data, the lowest-observed-adverse-effect level (LOAEL of the ethyl maltol and iron complexes was determined to be 1/81 LD50 (9.18 mg kg BW−1 day−1 in both male and female mice. Therefore, we suggest that alternative strategies for preparing the hot-pot, including the use of non-Fe-based cookware, need to be developed and encouraged to avoid the formation of the potentially toxic complexes.

  9. Characterization of in vitro glucuronidation clearance of a range of drugs in human kidney microsomes: comparison with liver and intestinal glucuronidation and impact of albumin.

    Science.gov (United States)

    Gill, Katherine L; Houston, J Brian; Galetin, Aleksandra

    2012-04-01

    Previous studies have shown the importance of the addition of albumin for characterization of hepatic glucuronidation in vitro; however, no reports exist on the effects of albumin on renal or intestinal microsomal glucuronidation assays. This study characterized glucuronidation clearance (CL(int, UGT)) in human kidney, liver, and intestinal microsomes in the presence and absence of bovine serum albumin (BSA) for seven drugs with differential UDP-glucuronosyltransferase (UGT) 1A9 and UGT2B7 specificity, namely, diclofenac, ezetimibe, gemfibrozil, mycophenolic acid, naloxone, propofol, and telmisartan. The impact of renal CL(int, UGT) on accuracy of in vitro-in vivo extrapolation (IVIVE) of glucuronidation clearance was investigated. Inclusion of 1% BSA for acidic drugs and 2% for bases/neutral drugs in incubations was found to be suitable for characterization of CL(int, UGT) in different tissues. Although BSA increased CL(int, UGT) in all tissues, the extent was tissue- and drug-dependent. Scaled CL(int, UGT) in the presence of BSA ranged from 2.22 to 207, 0.439 to 24.4, and 0.292 to 23.8 ml · min(-1) · g tissue(-1) in liver, kidney, and intestinal microsomes. Renal CL(int, UGT) (per gram of tissue) was up to 2-fold higher in comparison with that for liver for UGT1A9 substrates; in contrast, CL(int, UGT) for UGT2B7 substrates represented approximately one-third of hepatic estimates. Scaled renal CL(int, UGT) (in the presence of BSA) was up to 30-fold higher than intestinal glucuronidation for the drugs investigated. Use of in vitro data obtained in the presence of BSA and inclusion of renal clearance improved the IVIVE of glucuronidation clearance, with 50% of drugs predicted within 2-fold of observed values. Characterization and consideration of kidney CL(int, UGT) is particularly important for UGT1A9 substrates.

  10. Chemoenzymatic Synthesis, Characterization, and Scale-Up of Milk Thistle Flavonolignan Glucuronides

    Science.gov (United States)

    Gufford, Brandon T.; Graf, Tyler N.; Paguigan, Noemi D.; Oberlies, Nicholas H.

    2015-01-01

    Plant-based therapeutics, including herbal products, continue to represent a growing facet of the contemporary health care market. Mechanistic descriptions of the pharmacokinetics and pharmacodynamics of constituents composing these products remain nascent, particularly for metabolites produced following herbal product ingestion. Generation and characterization of authentic metabolite standards are essential to improve the quantitative mechanistic understanding of herbal product disposition in both in vitro and in vivo systems. Using the model herbal product, milk thistle, the objective of this work was to biosynthesize multimilligram quantities of glucuronides of select constituents (flavonolignans) to fill multiple knowledge gaps in the understanding of herbal product disposition and action. A partnership between clinical pharmacology and natural products chemistry expertise was leveraged to optimize reaction conditions for efficient glucuronide formation and evaluate alternate enzyme and reagent sources to improve cost effectiveness. Optimized reaction conditions used at least one-fourth the amount of microsomal protein (from bovine liver) and cofactor (UDP glucuronic acid) compared with typical conditions using human-derived subcellular fractions, providing substantial cost savings. Glucuronidation was flavonolignan-dependent. Silybin A, silybin B, isosilybin A, and isosilybin B generated five, four, four, and three monoglucuronides, respectively. Large-scale synthesis (40 mg of starting material) generated three glucuronides of silybin A: silybin A-7-O-β-d-glucuronide (15.7 mg), silybin A-5-O-β-d-glucuronide (1.6 mg), and silybin A-4´´-O-β-d-glucuronide (11.1 mg). This optimized, cost-efficient method lays the foundation for a systematic approach to synthesize and characterize herbal product constituent glucuronides, enabling an improved understanding of mechanisms underlying herbal product disposition and action. PMID:26316643

  11. In Vitro Glucuronidation of the Antibacterial Triclocarban and Its Oxidative MetabolitesS⃞

    Science.gov (United States)

    Schebb, N. H.; Franze, B.; Maul, R.; Ranganathan, A.

    2012-01-01

    Triclocarban (3,4,4′-trichlorocarbanilide; TCC) is widely used as an antibacterial in bar soaps. During use of these soaps, a significant portion of TCC is absorbed by humans. For the elimination from the body, glucuronidation plays a key role in both biliary and renal clearance. To investigate this metabolic pathway, we performed microsomal incubations of TCC and its hydroxylated metabolites 2′-OH-TCC, 3′-OH-TCC, and 6-OH-TCC. Using a new liquid chromatography-UV-mass spectrometry method, we could show a rapid glucuronidation for all OH-TCCs by the uridine-5′-diphosphate-glucuronosyltransferases (UGT) present in liver microsomes of humans (HLM), cynomolgus monkeys (CLM), rats (RLM), and mice (MLM). Among the tested human UGT isoforms, UGT1A7, UGT1A8, and UGT1A9 showed the highest activity for the conjugation of hydroxylated TCC metabolites followed by UGT1A1, UGT1A3, and UGT1A10. Due to this broad pattern of active UGTs, OH-TCCs can be efficiently glucuronidated in various tissues, as shown for microsomes from human kidney (HKM) and intestine (HIM). The major renal metabolites in humans, TCC-N-glucuronide and TCC-N′-glucuronide, were formed at very low conversion rates (TCC. These results present an anomaly where in vivo the predominant urinary metabolites of TCC are N and N′-glucuronides, but these compounds are slowly produced in vitro. PMID:21953915

  12. Glucuronidation of deoxynivalenol (DON) by different animal species: identification of iso-DON glucuronides and iso-deepoxy-DON glucuronides as novel DON metabolites in pigs, rats, mice, and cows.

    Science.gov (United States)

    Schwartz-Zimmermann, Heidi E; Hametner, Christian; Nagl, Veronika; Fiby, Iris; Macheiner, Lukas; Winkler, Janine; Dänicke, Sven; Clark, Erica; Pestka, James J; Berthiller, Franz

    2017-12-01

    The Fusarium mycotoxin deoxynivalenol (DON) is a frequent contaminant of cereal-based food and feed. Mammals metabolize DON by conjugation to glucuronic acid (GlcAc), the extent and regioselectivity of which is species-dependent. So far, only DON-3-glucuronide (DON-3-GlcAc) and DON-15-GlcAc have been unequivocally identified as mammalian DON glucuronides, and DON-7-GlcAc has been proposed as further DON metabolite. In the present work, qualitative HPLC-MS/MS analysis of urine samples of animals treated with DON (rats: 2 mg/kg bw, single bolus, gavage; mice: 1 mg/kg bw, single i.p. injection; pigs: 74 µg/kg bw, single bolus, gavage; cows: 5.2 mg DON/kg dry mass, oral for 13 weeks) revealed additional DON and deepoxy-DON (DOM) glucuronides. To elucidate their structures, DON and DOM were incubated with human (HLM) and rat liver microsomes (RLM). Besides the expected DON/DOM-3- and 15-GlcAc, minor amounts of four DON- and four DOM glucuronides were formed. Isolation and enzymatic hydrolysis of four of these compounds yielded iso-DON and iso-DOM, the identities of which were eventually confirmed by NMR. Incubation of iso-DON and iso-DOM with RLM and HLM yielded two main glucuronides for each parent compound, which were isolated and identified as iso-DON/DOM-3-GlcAc and iso-DON/DOM-8-GlcAc by NMR. Iso-DON-3-GlcAc, most likely misidentified as DON-7-GlcAc in the literature, proved to be a major DON metabolite in rats and a minor metabolite in pigs. In addition, iso-DON-8-GlcAc turned out to be one of the major DON metabolites in mice. DOM-3-GlcAc was the dominant DON metabolite in urine of cows and an important DON metabolite in rat urine. Iso-DOM-3-GlcAc was detected in urine of DON-treated rats and cows. Finally, DON-8,15-hemiketal-8-glucuronide, a previously described by-product of DON-3-GlcAc production by RLM, was identified in urine of DON-exposed mice and rats. The discovery of several novel DON-derived glucuronides in animal urine requires adaptation of

  13. Nitrosation Reactions of Ethyl Centralite

    Science.gov (United States)

    1977-02-01

    Colour Test Reagents. .. ......... .... 3 2.2 Procedures .. .. ........ .......... ... 4 2.2.1 Synthesis and Characterization of Ethyl Centralite (EC...8217-ethylcarbanilide 2,4 ,6-TNNNNEA 2 ,4,6-Trinitro-N-nitroso-N-ethylaniline NB Nitrobenzene NNNEA N-Nitroso-N-ethylaniline 3-NNNNEA 3-Nitro-N-Nitroso-N...ethyl aniline 4-NNNNEA 4-Nitro-N-Nitroso-N-ethylaniline 2-NA 2-Nitroanil ine 3-NA 3-Nitroaniline 4-NA 4-Nitroaniline 2,4,-VNA 2,4,-Dinitroaniline 2,4,6

  14. The UDP-Glucuronosyltransferase (UGT) 1A Polymorphism c.2042C>G (rs8330) Is Associated with Increased Human Liver Acetaminophen Glucuronidation, Increased UGT1A Exon 5a/5b Splice Variant mRNA Ratio, and Decreased Risk of Unintentional Acetaminophen-Induced Acute Liver FailureS⃞

    Science.gov (United States)

    Freytsis, Marina; Wang, Xueding; Peter, Inga; Guillemette, Chantal; Hazarika, Suwagmani; Duan, Su X.; Greenblatt, David J.; Lee, William M.

    2013-01-01

    Acetaminophen is cleared primarily by hepatic glucuronidation. Polymorphisms in genes encoding the acetaminophen UDP-glucuronosyltransferase (UGT) enzymes could explain interindividual variability in acetaminophen glucuronidation and variable risk for liver injury after acetaminophen overdose. In this study, human liver bank samples were phenotyped for acetaminophen glucuronidation activity and genotyped for the major acetaminophen-glucuronidating enzymes (UGTs 1A1, 1A6, 1A9, and 2B15). Of these, only three linked single nucleotide polymorphisms (SNPs) located in the shared UGT1A-3′UTR region (rs10929303, rs1042640, rs8330) were associated with acetaminophen glucuronidation activity, with rs8330 consistently showing higher acetaminophen glucuronidation at all the tested concentrations of acetaminophen. Mechanistic studies using luciferase-UGT1A-3′UTR reporters indicated that these SNPs do not alter mRNA stability or translation efficiency. However, there was evidence for allelic imbalance and a gene-dose proportional increase in the amount of exon 5a versus exon 5b containing UGT1A mRNA spliced transcripts in livers with the rs8330 variant allele. Cotransfection studies demonstrated an inhibitory effect of exon 5b containing cDNAs on acetaminophen glucuronidation by UGT1A1 and UGT1A6 cDNAs containing exon 5a. In silico analysis predicted that rs8330 creates an exon splice enhancer site that could favor exon 5a (over exon 5b) utilization during splicing. Finally, the prevalence of rs8330 was significantly lower (P = 0.027, χ2 test) in patients who had acute liver failure from unintentional acetaminophen overdose compared with patients with acute liver failure from other causes or a race- or ethnicity-matched population. Together, these findings suggest that rs8330 is an important determinant of acetaminophen glucuronidation and could affect an individual’s risk for acetaminophen-induced liver injury. PMID:23408116

  15. Pharmacology of morphine and morphine-3-glucuronide at opioid, excitatory amino acid, GABA and glycine binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Bartlett, S.E.; Smith, M.T. (Department of Pharmacy, The University of Queensland (Australia)); Dood, P.R. (Clinical Research Centre, Royal Brisbane Hospital Foundation, Brisbane (Australia))

    1994-07-01

    Morphine in high doses and its major metabolite, morphine-3-glucuronide, cause CNS excitation following intrathecal and intracerebroventricular administration by an unknown mechanism. This study investigated whether morphine and morphine-3-glucuronide interact at major excitatory (glutamate), major inhibitory (GABA or glycine), or opioid binding sites. Homogenate binding assays were performed using specific radioligands. At opioid receptors, morphine-3-glucuronide and morphine caused an equipotent sodium shift, consistent with morphine-3-glucuronide behaving as an agonist. This suggests that morphine-3-glucuronide-mediated excitation is not caused by an interaction at opioid receptors. Morphine-3-glucuronide and morphine caused a weak inhibition of the binding of [sup 3]H-MK801 (non-competitive antagonist) and [sup 125]I-ifenprodil (polyamine site antagonist), but at unphysiologically high concentrations. This suggests that CNS excitation would not result from an interaction of morphine-3-glucuronide and high-dose morphine with these sites on the NMDA receptor. Morphine-3-glucuronide and morphine inhibited the binding of [sup 3]H-muscimol (GABA receptor agonist), [sup 3]H-diazepam and [sup 3]H-flunitraxepam (benzodiazepine agonists) binding very weakly, suggesting the excitatory effects of morphine-3-glucuronide and high-dose morphine are not elicited through GABA[sub A] receptors. Morphine-3-glucuronide and high-dose morphine did not prevent re-uptake of glutamate into presynaptic nerve terminals. In addition, morphine-3-glucuronide and morphine did not inhibit the binding of [sup 3]H-strychnine (glycine receptor antagonist) to synaptic membranes prepared from bovine spinal cord. It is concluded that excitation caused by high-dose morphine and morphine-3-glucuronide is not mediated by an interaction with postsynaptic amino acid receptors. (au) (30 refs.).

  16. 21 CFR 184.1293 - Ethyl alcohol.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethyl alcohol. 184.1293 Section 184.1293 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1293 Ethyl alcohol. (a) Ethyl alcohol (ethanol) is the chemical C2H5OH. (b...

  17. 21 CFR 172.868 - Ethyl cellulose.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethyl cellulose. 172.868 Section 172.868 Food and... Multipurpose Additives § 172.868 Ethyl cellulose. The food additive ethyl cellulose may be safely used in food in accordance with the following prescribed conditions: (a) The food additive is a cellulose ether...

  18. 21 CFR 573.420 - Ethyl cellulose.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ethyl cellulose. 573.420 Section 573.420 Food and... Listing § 573.420 Ethyl cellulose. The food additive ethyl cellulose may be safely used in animal feed in accordance with the following prescribed conditions: (a) The food additive is a cellulose ether containing...

  19. 27 CFR 21.107 - Ethyl acetate.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Ethyl acetate. 21.107....107 Ethyl acetate. (a) 85 percent ester: (1) Acidity (as acetic acid). Not more than 0.015 percent by...); for incorporation by reference, see § 21.6(b).) When 100 ml of ethyl acetate are distilled by this...

  20. Identification of human UDP-glucuronosyltransferases involved in N-carbamoyl glucuronidation of lorcaserin.

    Science.gov (United States)

    Sadeque, Abu J M; Usmani, Khawja A; Palamar, Safet; Cerny, Matthew A; Chen, Weichao G

    2012-04-01

    Lorcaserin, a selective serotonin 5-HT(2C) receptor agonist, is a weight management agent in clinical development. Lorcaserin N-carbamoyl glucuronidation governs the predominant excretory pathway of lorcaserin in humans. Human UDP-glucuronosyltransferases (UGTs) responsible for lorcaserin N-carbamoyl glucuronidation are identified herein. Lorcaserin N-carbamoyl glucuronide formation was characterized by the following approaches: metabolic screening using human tissues (liver, kidney, intestine, and lung) and recombinant enzymes, kinetic analyses, and inhibition studies. Whereas microsomes from all human tissues studied herein were found to be catalytically active for lorcaserin N-carbamoyl glucuronidation, liver microsomes were the most efficient. With recombinant UGT enzymes, lorcaserin N-carbamoyl glucuronidation was predominantly catalyzed by three UGT2Bs (UGT2B7, UGT2B15, and UGT2B17), whereas two UGT1As (UGT1A6 and UGT1A9) played a minor role. UGT2B15 was most efficient, with an apparent K(m) value of 51.6 ± 1.9 μM and V(max) value of 237.4 ± 2.8 pmol/mg protein/min. The rank order of catalytic efficiency of human UGT enzymes for lorcaserin N-carbamoyl glucuronidation was UGT2B15 > UGT2B7 > UGT2B17 > UGT1A9 > UGT1A6. Inhibition of lorcaserin N-carbamoyl glucuronidation activities of UGT2B7, UGT2B15, and UGT2B17 in human liver microsomes by mefenamic acid, bisphenol A, and eugenol further substantiated the involvement of these UGT2B isoforms. In conclusion, multiple human UGT enzymes catalyze N-carbamoyl glucuronidation of lorcaserin; therefore, it is unlikely that inhibition of any one of these UGT activities will lead to significant inhibition of the lorcaserin N-carbamoyl glucuronidation pathway. Thus, the potential for drug-drug interaction by concomitant administration of a drug(s) that is metabolized by any of these UGTs is remote.

  1. Human UGT2B7 is the major isoform responsible for the glucuronidation of clopidogrel carboxylate.

    Science.gov (United States)

    Ji, Jin-Zi; Huang, Bei-Bei; Gu, Tong-Tong; Tai, Ting; Zhou, Huan; Jia, Yu-Meng; Mi, Qiong-Yu; Zhang, Meng-Ran; Xie, Hong-Guang

    2018-02-01

    Clopidogrel is predominantly hydrolyzed to clopidogrel carboxylic acid (CCA) by carboxylesterase 1, and subsequently CCA is glucuronidated to clopidogrel acyl glucuronide (CAG) by uridine diphosphate-glucuronosyltransferases (UGTs); however, the UGT isoenzymes glucuronidating CCA remain unidentified to date. In this study, the glucuronidation of CCA was screened with pooled human liver microsomes (HLMs) and 7 human recombinant UGT (rUGT) isoforms. Results indicated that rUGT2B7 exhibited the highest catalytical activity for the CCA glucuronidation as measured with a mean Vmax value of 120.9 pmol/min/mg protein, 3- to 12-fold higher than that of the other rUGT isoforms tested. According to relative activity factor approach, the relative contribution of rUGT2B7 to CCA glucuronidation was estimated to be 58.6%, with the minor contributions (3%) from rUGT1A9. Moreover, the glucuronidation of CCA followed Michaelis-Menten kinetics with a mean Km value of 372.9 μM and 296.4 μM for pooled HLMs and rUGT2B7, respectively, showing similar affinity for both. The formation of CAG was significantly inhibited by azidothymidine and gemfibrozil (well-characterized UGT2B7 substrates) in a concentration-dependent manner, or by fluconazole (a typical UGT2B7-selective inhibitor) in a time-dependent manner, for both HLMs and rUGT2B7, respectively. In addition, CCA inhibited azidothymidine glucuronidation (catalyzed almost exclusively by UGT2B7) by HLMs and rUGT2B7 in a concentration-dependent manner, indicating that CCA is a substrate of UGT2B7. These results reveal that UGT2B7 is the major enzyme catalyzing clopidogrel glucuronidation in the human liver, and that there is the potential for drug-drug interactions between clopidogrel and the other substrate drugs of UGT2B7. Copyright © 2017 John Wiley & Sons, Ltd.

  2. Ovarian Hormone Estrone Glucuronide (E1G) quantification-impedimetric electrochemical spectroscopy approach

    KAUST Repository

    Zia, Asif I.

    2013-12-01

    A study was conducted on detection and concentration measurement of estrone glucuronide (E1G), an important metabolite of the ovarian hormone estradiol, by using Electrochemical Impedance Spectroscopy (EIS) technique. A miniature planar Inter-digital (ID) capacitive sensor fabricated on single crystal silicon substrate with sputtered gold electrodes coupled with EIS was used to measure conductivity, permeability and dielectric properties of the said hormone metabolite. A thin film of Silicon Nitride (50 um) was coated on the sensor as passivation layer to avoid Faradic currents through the sensor. Impedance spectrums were obtained with various concentrations of E1G in buffer solution by exposing the samples to electrical perturbations at certain frequency range. Relationship of sample conductance with E1G concentration was studied on basis Randle\\'s equivalent circuit model and results were analyzed to deduce Constant Phase Equivalent (CPE) Circuit model in order to evaluate the double layer capacitance produced at the solution-electrode interface due to kinetic processes taking place in the electrochemical cell. The sensitivity of the sensor was evaluated against concentration. The result analysis confirmed that fabricated ID sensor together with EIS can provide a rapid and successful low cost sensing system which can help a lay user to determine peak time for feminine reproductive fertility at home without submitting samples for an expensive and time consuming laboratory test. © 2013 IEEE.

  3. Limitations of EMIT benzodiazepine immunoassay for monitoring compliance of patients with benzodiazepine therapy even after hydrolyzing glucuronide metabolites in urine to increase cross-reactivity: comparison of immunoassay results with LC-MS/MS values.

    Science.gov (United States)

    Dixon, R Brent; Floyd, Diana; Dasgupta, Amitava

    2015-02-01

    Benzodiazepines are widely prescribed, and compliance of patients with benzodiazepine therapy is often monitored using urine specimens. Although various commercially available benzodiazepines immunoassays are widely used for compliance monitoring, such immunoassays usually have low cross-reactivity with glucuronide metabolites. We studied the effect of hydrolyzing such glucuronide before analysis to reevaluate suitability of Enzyme multiplied immunoassay technique benzodiazepine immunoassay for monitoring compliance with benzodiazepine therapy. In 31 urine specimens collected from patients taking benzodiazepines, the true analyte concentrations were determined (after hydrolyzing glucuronide metabolites using beta-glucuronidase) using liquid chromatography-tandem mass spectrometry. These urine specimens were reanalyzed using EMIT benzodiazepine assay (Flex Reagent Cartridge; Siemens Diagnostics) and Vista analyzer. We observed false negative test results with EMIT in 11 of 31 specimens analyzed where liquid chromatography-tandem mass spectrometry values were above the 200 ng/mL cutoff concentration, but EMIT benzodiazepine assay showed a negative result, indicating that despite hydrolysis of the specimen to liberate parent drug (glucuronide metabolite often has poor cross-reactivity), the false negative rate using EMIT assay was 35.5%. Patient compliance with benzodiazepine therapy must be monitored using a chromatographic method.

  4. Influence of renal function on the elimination of morphine and morphine glucuronides

    DEFF Research Database (Denmark)

    Wolff, Jesper; Bigler, Dennis Richard; Christensen, C B

    1988-01-01

    The influence of renal function, measured by 51Cr-EDTA clearance, on morphine and morphine glucuronide kinetics has been studied in 13 patients after a single i.v. injection of morphine. Unconjugated morphine and morphine glucuronides were measured by a sensitive, specific RIA after extraction from...... plasma. No significant correlation was found between total body clearance of unconjugated morphine and 51Cr-EDTA clearance. However, patients with renal insufficiency had impaired elimination of morphine glucuronides, and the apparent clearance was significantly correlated with the 51Cr-EDTA clearance (r...... = 0.94, p less than 0.001). A relatively long terminal elimination of half-life of morphine was found in all patients (mean +/- SD: 9.2 +/- 2.5 h), irrespective of glomerular function....

  5. Pharmacokinetics of morphine-6-glucuronide following oral administration in healthy volunteers

    DEFF Research Database (Denmark)

    Villesen, Hanne H.; Kristensen, Kim; Hansen, Steen Honoré

    2007-01-01

    After oral administration, morphine-6-glucuronide (M6G) displays an atypical absorption profile with two peak plasma concentrations. A proposed explanation is that M6G is hydrolysed to morphine in the colon, which is then absorbed and subsequently undergoes metabolism in the liver to morphine-3......-glucuronide (M3G) and M6G. The aims of this study were to confirm and elucidate the biphasic absorption profile as well as clarify the conversion of M6G to morphine after a single oral administration of M6G in healthy volunteers....

  6. Effects of pesticide (Chlorpyrifos Ethyl) on the fingerlings of catfish ...

    African Journals Online (AJOL)

    Acute toxicity bioassay of the organophosphate pesticide chlorpyrifos ethyl on the fingerlings of Clarias gariepinus was evaluated to determine its effect on the survival, body morphology and the lethal concentration (LC50). Following a preliminary bioassay in mg/l concentration which showed 100% mortality, fish were ...

  7. Nitrosation of glycine ethyl ester and ethyl diazoacetate to give the alkylating agent and mutagen ethyl chloro(hydroximino)acetate.

    Science.gov (United States)

    Zhou, Lin; Haorah, James; Chen, Sheng C; Wang, Xiaojie; Kolar, Carol; Lawson, Terence A; Mirvish, Sidney S

    2004-03-01

    Whereas nitrosation of secondary amines produces nitrosamines, amino acids with primary amino groups and glycine ethyl ester were reported to react with nitrite to give unidentified agents that alkylated 4-(p-nitrobenzyl)pyridine to produce purple dyes and be direct mutagens in the Ames test. We report here that treatment of glycine ethyl ester at 37 degrees C with excess nitrite acidified with HCl, followed by ether extraction, gave 30-40% yields of a product identified as ethyl chloro(hydroximino)acetate [ClC(=NOH)COOEt, ECHA] and a 9% yield of ethyl chloroacetate. The ECHA was identical to that synthesized by a known method from ethyl acetoacetate, strongly alkylated nitrobenzylpyridine, and may have arisen by N-nitrosation of glycine ethyl ester to give ethyl diazoacetate, which was C-nitrosated and reacted with chloride to give ECHA. Nitrosation of ethyl diazoacetate also yielded ECHA. Ethyl nitroacetate was not an intermediate as its nitrosation did not produce ECHA. ECHA reacted with aniline to give ethyl (hydroxamino)(phenylimino)acetate [PhN=C(NHOH)CO2Et]. This product was different from ethyl [(phenylamino)carbonyl]carbamate [PhNHC(=O)NHCO2Et], which was synthesized by reacting ethyl isocyanatoformate (OCN.CO2Et) with aniline. ECHA reacted with guanosine to give a derivative, which may have been a guanine-C(=NOH)CO2Et derivative. ECHA showed moderate toxicity and weak but significant mutagenicity without activation in Salmonella typhimurium TA-100 (mean, 1.31 x control value for 12-18 microg/plats) and for V79 mammalian cells (1.5-1.7 x control value for 60-100 microM). In conclusion, gastric nitrosation of glycine derivatives such as peptides with a N-terminal glycine might produce ECHA analogues that alkylate bases of gastric mucosal DNA and thereby initiate gastric cancer.

  8. Pallidol hexaacetate ethyl acetate monosolvate

    Directory of Open Access Journals (Sweden)

    Qinyong Mao

    2013-07-01

    Full Text Available The entire molecule of pallidol hexaacetate {systematic name: (±-(4bR,5R,9bR,10R-5,10-bis[4-(acetyloxyphenyl]-4b,5,9b,10-tetrahydroindeno[2,1-a]indene-1,3,6,8-tetrayl tetraacetate} is completed by the application of twofold rotational symmetry in the title ethyl acetate solvate, C40H34O12·C4H8O2. The ethyl acetate molecule was highly disordered and was treated with the SQUEEZE routine [Spek (2009. Acta Cryst. D65, 148–155]; the crystallographic data take into account the presence of the solvent. In pallidol hexaacetate, the dihedral angle between the fused five-membered rings (r.m.s. deviation = 0.100 Å is 54.73 (6°, indicating a significant fold in the molecule. Significant twists between residues are also evident as seen in the dihedral angle of 80.70 (5° between the five-membered ring and the pendent benzene ring to which it is attached. Similarly, the acetate residues are twisted with respect to the benzene ring to which they are attached [C—O(carboxy—C—C torsion angles = −70.24 (14, −114.43 (10 and −72.54 (13°]. In the crystal, a three-dimensional architecture is sustained by C—H...O interactions which encompass channels in which the disordered ethyl acetate molecules reside.

  9. Mrp2 is essential for estradiol-17 beta(beta-D-glucuronide)-induced cholestasis in rats

    NARCIS (Netherlands)

    Huang, LY; Smit, JW; Meijer, DKF; Vore, M

    The present study evaluates the roles of the multidrug resistance-1 P-glycoprotein, Mdr1a/1b, the bile salt export pump (Bsep), and the multidrug resistance-associated protein-2 (Mrp2) in mediating cholestasis induced by estradiol-17 beta(beta-D-glucuronide) (E(2)17G). Administration of [H-3]E(2)17G

  10. Effect of Glucuronidation on the Potential of Kaempferol to Inhibit Serine/Threonine Protein Kinases

    NARCIS (Netherlands)

    Beekmann, Karsten; Haan, De Laura H.J.; Actis-Goretta, Lucas; Bladeren, Van Peter J.; Rietjens, Ivonne M.C.M.

    2016-01-01

    To study the effect of metabolic conjugation of flavonoids on the potential to inhibit protein kinase activity, the inhibitory effects of the dietary flavonol kaempferol and its major plasma conjugate kaempferol-3-O-glucuronide on protein kinases were studied. To this end, the inhibition of the

  11. Developmental changes rather than repeated administration drive paracetamol glucuronidation in neonates and infants

    NARCIS (Netherlands)

    E.H.J. Krekels (Elke); S. Van Ham (Saskia); K.M. Allegaert (Karel); J.N. de Hoon; D. Tibboel (Dick); M. Danhof (Meindert); C.A.J. Knibbe (Catherijne)

    2015-01-01

    textabstractPurpose: Based on recovered metabolite ratios in urine, it has been concluded that paracetamol glucuronidation may be up-regulated upon multiple dosing. This study investigates paracetamol clearance in neonates and infants after single and multiple dosing using a population modelling

  12. The Escherichia coli glucuronylsynthase promoted synthesis of steroid glucuronides: improved practicality and broader scope.

    Science.gov (United States)

    Ma, Paul; Kanizaj, Nicholas; Chan, Shu-Ann; Ollis, David L; McLeod, Malcolm D

    2014-08-28

    A library of steroid glucuronides was prepared using the glucuronylsynthase derived from Escherichia coliβ-glucuronidase, followed by purification using solid-phase extraction. A representative range of steroid substrates were screened for synthesis on the milligram scale under optimised conditions with conversions dependent on steroid substitution and stereochemistry. Epiandrosterone (3β-hydroxy-5α-androstan-17-one) provided the highest conversion of 90% (84% isolated yield). The previously unreported glucuronide conjugates of methandriol (17α-methylandrost-5-ene-3β,17β-diol), cholest-5-ene-3β,25-diol and the designer steroid trenazone (17β-hydroxyestra-4,9-dien-3-one) were prepared on a multi-milligram scale suitable for characterisation by (1)H and (13)C NMR spectroscopy. The glucuronide conjugate of d5-etiocholanolone (2,2,3,4,4-d5-3α-hydroxy-5β-androstan-17-one), a target developed by the World Anti-Doping Agency as a certified reference material, was also prepared on a milligram scale. The improved E. coli glucuronylsynthase method provides for the rapid synthesis and purification of steroid glucuronides on a scale suitable for a range of analytical applications.

  13. Developmental changes rather than repeated administration drive paracetamol glucuronidation in neonates and infants.

    Science.gov (United States)

    Krekels, Elke H J; van Ham, Saskia; Allegaert, Karel; de Hoon, Jan; Tibboel, Dick; Danhof, Meindert; Knibbe, Catherijne A J

    2015-09-01

    Based on recovered metabolite ratios in urine, it has been concluded that paracetamol glucuronidation may be up-regulated upon multiple dosing. This study investigates paracetamol clearance in neonates and infants after single and multiple dosing using a population modelling approach. A population pharmacokinetic model was developed in NONMEM VI, based on paracetamol plasma concentrations from 54 preterm and term neonates and infants, and on paracetamol, paracetamol-glucuronide and paracetamol-sulphate amounts in urine from 22 of these patients. Patients received either a single intravenous propacetamol dose or up to 12 repeated doses. Paracetamol and metabolite disposition was best described with one-compartment models. The formation clearance of paracetamol-sulphate was 1.46 mL/min/kg(1.4), which was about 5.5 times higher than the formation clearance of the glucuronide of 0.266 mL/min/kg. The renal excretion rate constants of both metabolites was estimated to be 11.4 times higher than the excretion rate constant of unchanged paracetamol, yielding values of 0.580 mL/min/kg. Developmental changes were best described by bodyweight in linear relationships on the distribution volumes, the formation of paracetamol-glucuronide and the unchanged excretion of paracetamol, and in an exponential relationship on the formation of paracetamol-sulphate. There was no evidence for up-regulation or other time-varying changes in any of the model parameters. Simulations with this model illustrate how paracetamol-glucuronide recovery in urine increases over time due to the slower formation of this metabolite and in the absence of up-regulation. Developmental changes, described by bodyweight-based functions, rather than up-regulation, explain developmental changes in paracetamol disposition in neonates and infants.

  14. Mass spectrometric characterization of glucuronides formed by a new concept, combining Cunninghamella elegans with TEMPO.

    Science.gov (United States)

    Rydevik, Axel; Bondesson, Ulf; Thevis, Mario; Hedeland, Mikael

    2013-10-01

    A new concept for the production of drug glucuronides is presented and the products formed were characterized using ultra high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). Glucuronic acid conjugates are important phase II metabolites of a wide range of drugs. There is a lack of commercially available glucuronides and classic synthetic methods are tedious and expensive. Thus, new methods of glucuronide synthesis are needed. Selective androgen receptor modulators (SARMs) of the aryl propionamide class were used as model compounds and were incubated with the fungus Cunninghamella elegans which was previously known to conjugate drugs with glucose. The resulting glucoside metabolites were then oxidized with tetramethylpiperidinyl-1-oxy (TEMPO). UPLC-HRMS analysis showed that the peaks corresponding to the glucosides had disappeared after the reaction and were replaced by peaks with m/z consistent with the corresponding glucuronic acid conjugates. The MS/MS spectra of the reaction products were investigated and the observed fragment ion pattern corroborated the suggested structural change. A comparison in terms of retention times and product ion spectra between the glucuronides formed by the new method and those produced by liver microsomes indicated that the conjugates from the two different sources were identical, thus demonstrating the human relevance of the presented technique. Furthermore, the glucuronides formed by the presented method were readily hydrolyzed by β-glucuronidase which further gave evidence as to the fact that they were of β configuration. The investigated method was easy to perform, required a low input of work and had a low cost. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. An orphan esterase ABHD10 modulates probenecid acyl glucuronidation in human liver.

    Science.gov (United States)

    Ito, Yusuke; Fukami, Tatsuki; Yokoi, Tsuyoshi; Nakajima, Miki

    2014-12-01

    Probenecid, a widely used uricosuric agent, is mainly metabolized to probenecid acyl glucuronide (PRAG), which is considered a causal substance of severe allergic or anaphylactoid reactions. PRAG can be hydrolyzed (deglucuronidated) to probenecid. The purpose of this study was to identify enzymes responsible for probenecid acyl glucuronidation and PRAG deglucuronidation in human livers and to examine the effect of deglucuronidation in PRAG formation. In human liver homogenates (HLHs), the intrinsic clearance (CLint) of PRAG deglucuronidation was much greater (497-fold) than that of probenecid acyl glucuronidation. Evaluation of PRAG formation by recombinant UDP-glucuronosyltransferase (UGT) isoforms and an inhibition study using HLHs as an enzyme source demonstrated that multiple UGT isoforms, including UGT1A1, UGT1A9, and UGT2B7, catalyzed probenecid acyl glucuronidation. We found that recombinant α/β hydrolase domain containing 10 (ABHD10) substantially catalyzed PRAG deglucuronidation activity, whereas carboxylesterases did not. Similar inhibitory patterns by chemicals between HLHs and recombinant ABHD10 supported the major contribution of ABHD10 to PRAG deglucuronidation in human liver. Interestingly, it was demonstrated that the CLint value of probenecid acyl glucuronidation in HLHs was increased by 1.7-fold in the presence of phenylmethylsulfonyl fluoride, which potently inhibited ABHD10 activity. In conclusion, we found that PRAG deglucuronidation catalyzed by ABHD10 suppressively regulates PRAG formation via multiple UGT enzymes in human liver. The balance of activities by these enzymes is important for the formation of PRAG, which may be associated with the adverse reactions observed after probenecid administration. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  16. Role of glucuronidation for hepatic detoxification and urinary elimination of toxic bile acids during biliary obstruction.

    Directory of Open Access Journals (Sweden)

    Martin Perreault

    Full Text Available Biliary obstruction, a severe cholestatic condition, results in a huge accumulation of toxic bile acids (BA in the liver. Glucuronidation, a conjugation reaction, is thought to protect the liver by both reducing hepatic BA toxicity and increasing their urinary elimination. The present study evaluates the contribution of each process in the overall BA detoxification by glucuronidation. Glucuronide (G, glycine, taurine conjugates, and unconjugated BAs were quantified in pre- and post-biliary stenting urine samples from 12 patients with biliary obstruction, using liquid chromatography-tandem mass spectrometry (LC-MS/MS. The same LC-MS/MS procedure was used to quantify intra- and extracellular BA-G in Hepatoma HepG2 cells. Bile acid-induced toxicity in HepG2 cells was evaluated using MTS reduction, caspase-3 and flow cytometry assays. When compared to post-treatment samples, pre-stenting urines were enriched in glucuronide-, taurine- and glycine-conjugated BAs. Biliary stenting increased the relative BA-G abundance in the urinary BA pool, and reduced the proportion of taurine- and glycine-conjugates. Lithocholic, deoxycholic and chenodeoxycholic acids were the most cytotoxic and pro-apoptotic/necrotic BAs for HepG2 cells. Other species, such as the cholic, hyocholic and hyodeoxycholic acids were nontoxic. All BA-G assayed were less toxic and displayed lower pro-apoptotic/necrotic effects than their unconjugated precursors, even if they were able to penetrate into HepG2 cells. Under severe cholestatic conditions, urinary excretion favors the elimination of amidated BAs, while glucuronidation allows the conversion of cytotoxic BAs into nontoxic derivatives.

  17. 27 CFR 21.108 - Ethyl ether.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Ethyl ether. 21.108 Section 21.108 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT....108 Ethyl ether. (a) Odor. Characteristic odor. (b) Specific gravity at 15.56 °/15.56 °C. Not more...

  18. Direct analysis of salicylic acid, salicyl acyl glucuronide, salicyluric acid and gentisic acid in human plasma and urine by high-performance liquid chromatography.

    Science.gov (United States)

    Liu, J H; Smith, P C

    1996-01-12

    A method for the simultaneous direct determination of salicylate (SA), its labile, reactive metabolite, salicyl acyl glucuronide (SAG), and two other major metabolites, salicyluric acid and gentisic acid in plasma and urine is described. Isocratic reversed-phase high performance liquid chromatography (HPLC) employed a 15-cm C18 column using methanol-acetonitrile-25 mM acetic acid as the mobile phase, resulting in HPLC analysis time of less than 20 min. Ultraviolet detection at 310 nm permitted analysis of SAG in plasma, but did not provide sensitivity for measurement of salicyl phenol glucuronide. Plasma or urine samples are stabilized immediately upon collection by adjustment of pH to 3-4 to prevent degradation of the labile acyl glucuronide metabolite. Plasma is then deproteinated with acetonitrile, dried and reconstituted for injection, whereas urine samples are simply diluted prior to injection on HPLC. m-Hydroxybenzoic acid served as the internal standard. Recoveries from plasma were greater than 85% for all four compounds over a range of 0.2-20 micrograms/ml and linearity was observed from 0.1-200 micrograms/ml and 5-2000 micrograms/ml for SA in plasma and urine, respectively. The method was validated to 0.2 microgram/ml, thus allowing accurate measurement of SA, and three major metabolites in plasma and urine of subjects and small animals administered salicylates. The method is unique by allowing quantitation of reactive SAG in plasma at levels well below 1% that of the parent compound, SA, as is observed in patients administered salicylates.

  19. Transformation of codeine and codeine-6-glucuronide to opioid analogues by urine adulteration with pyridinium chlorochromate: potential issue for urine drug testing.

    Science.gov (United States)

    Luong, Susan; Ung, Alison T; Kalman, John; Fu, Shanlin

    2014-07-30

    Pyridinium chlorochromate (PCC) is the active ingredient of 'Urine Luck', a commercially available in vitro adulterating agent used to conceal the presence of drugs in a urine specimen. The exposure of codeine and its major glucuronide metabolite codeine-6-glucuronide (C6G) to PCC was investigated to determine whether PCC is an effective masking agent for these opiate compounds. Following the addition of PCC to both spiked and authentic codeine and C6G-positive urine specimens, the samples were monitored using liquid chromatography/mass spectrometry (LC/MS). Stable reaction products were identified and characterized using high-resolution MS analysis and, where possible, nuclear magnetic resonance (NMR) analysis. It was determined that PCC effectively oxidizes codeine and C6G, thus altering the original codeine-to-C6G ratio in the urine specimen. Four reaction products were identified for codeine: codeinone, 14-hydroxycodeinone, 6-O-methylcodeine and 8-hydroxy-7,8-dihydrocodeinone. Similarly, three reaction products were identified for C6G: codeinone, codeine and a lactone of C6G (tentative assignment). Besides addressing the complications added to interpretation, more investigation is warranted to further determine their potential for use as markers for monitoring the presence of codeine and C6G in urine specimens adulterated with PCC. Copyright © 2014 John Wiley & Sons, Ltd.

  20. Soy isoflavone metabolism in cats compared with other species: Urinary metabolite concentrations and glucuronidation by liver microsomes

    OpenAIRE

    Redmon, Joanna M.; Shrestha, Binu; Cerundolo, Rosario; Court, Michael H.

    2015-01-01

    Soybean is a common source of protein in many pet foods. Slow glucuronidation of soy-derived isoflavones in cats has been hypothesized to result in accumulation with adverse health consequences. Here we evaluated species’ differences in soy isoflavone glucuronidation using urine samples from cats and dogs fed a soy-based diet and liver microsomes from cats compared with microsomes from 12 other species.Significant concentrations of conjugated (but not unconjugated) genistein, daidzein, and gl...

  1. Bisphenol-A glucuronidation in human liver and breast: identification of UDP-glucuronosyltransferases (UGTs) and influence of genetic polymorphisms.

    Science.gov (United States)

    Street, Christina M; Zhu, Zhaohui; Finel, Moshe; Court, Michael H

    2017-01-01

    1. Bisphenol-A is a ubiquitous environmental contaminant that is primarily metabolized by glucuronidation and associated with various human diseases including breast cancer. Here we identified UDP-glucuronosyltransferases (UGTs) and genetic polymorphisms responsible for interindividual variability in bisphenol-A glucuronidation in human liver and breast. 2. Hepatic UGTs showing the highest bisphenol-A glucuronidation activity included UGT2B15 and UGT1A9. Relative activity factor normalization indicated that UGT2B15 contributes >80% of activity at bisphenol-A concentrations under 5 μM, while UGT1A9 contributes up to 50% of activity at higher concentrations. 3. Bisphenol-A glucuronidation by liver microsomes (46 donors) ranged from 0.25 to 4.3 nmoles/min/mg protein. Two-fold higher glucuronidation (p = 0.018) was observed in UGT1A9 *22/*22 livers compared with *1/*1 and *1/*22 livers. However, no associations were observed for UGT2B15*2 or UGT1A1*28 genotypes. 4. Bisphenol-A glucuronidation by breast microsomes (15 donors) ranged from bisphenol-A was highest for UGT1A1, followed by UGT2B4, UGT1A9, UGT1A10, UGT2B7 and UGT2B15. Bisphenol-A glucuronidation was over 10-fold lower in breast tissues with the UGT1A1*28 allele compared with tissues without this allele (p = 0.006). 5. UGT2B15 and UGT1A9 contribute to glucuronidation variability in liver, while UGT1A1 is important in breast.

  2. Soy isoflavone metabolism in cats compared with other species: Urinary metabolite concentrations and glucuronidation by liver microsomes

    Science.gov (United States)

    Redmon, Joanna M.; Shrestha, Binu; Cerundolo, Rosario; Court, Michael H.

    2016-01-01

    Soybean is a common source of protein in many pet foods. Slow glucuronidation of soy-derived isoflavones in cats has been hypothesized to result in accumulation with adverse health consequences. Here we evaluated species’ differences in soy isoflavone glucuronidation using urine samples from cats and dogs fed a soy-based diet and liver microsomes from cats compared with microsomes from 12 other species.Significant concentrations of conjugated (but not unconjugated) genistein, daidzein, and glycitein, and the gut microbiome metabolites, dihydrogenistein and dihydrodaidzein were found in cat and dog urine samples. Substantial amounts of conjugated equol were also found in cat urine but not in dog urine.β-glucuronidase treatment showed that all these compounds were significantly glucuronidated in dog urine while only daidzein (11%) and glycitein (37%) showed any glucuronidation in cat urine suggesting that alternate metabolic pathways including sulfation predominate in cats.Glucuronidation rates of genistein, daidzein, and equol by cat livers were consistently ranked within the lowest three out of 13 species’ livers evaluated. Ferret and mongoose livers were also ranked in the lowest four species.Our results demonstrate that glucuronidation is a minor pathway for soy isoflavone metabolism in cats compared with most other species. PMID:26366946

  3. Improved Synthesis of the C-Glucuronide/Glycoside of 4-Hydroxybenzylretinone (4-HBR).

    Science.gov (United States)

    Cavanaugh, Kathryn R; Narayanasamy, Sureshbabu; Walker, Joel R; Clagett-Dame, Margaret; Curley, Robert W

    2016-01-01

    Improvements in the synthesis of carbon-linked glucuronide/glucoside conjugates of cancer chemopreventive retinoids have been achieved starting with 2,3,4,6-tetra-O-benzyl-D-glucopyranose. The revised approach demonstrates better yields, eliminates the use of an expensive, carcinogenic protecting group reagent, and avoids much painstaking chromatography. The new approach should allow synthesis of larger quantities of the agents for detailed animal and mechanistic studies.

  4. Milk Thistle Constituents Inhibit Raloxifene Intestinal Glucuronidation: A Potential Clinically Relevant Natural Product–Drug Interaction

    OpenAIRE

    Gufford, Brandon T.; CHEN, Gang; Vergara, Ana G.; Lazarus, Philip; Oberlies, Nicholas H.; Paine, Mary F.

    2015-01-01

    Women at high risk of developing breast cancer are prescribed selective estrogen response modulators, including raloxifene, as chemoprevention. Patients often seek complementary and alternative treatment modalities, including herbal products, to supplement prescribed medications. Milk thistle preparations, including silibinin and silymarin, are top-selling herbal products that may be consumed by women taking raloxifene, which undergoes extensive first-pass glucuronidation in the intestine. Ke...

  5. Metabolic comparison of radiolabeled bleomycin and bleomycin-glucuronide labeled with 99mTc.

    Science.gov (United States)

    Koçan, Feray; Avcıbaşı, Ugur; Unak, Perihan; Müftüler, Fazilet Zümrüt Biber; Içhedef, Cigdem A; Demiroğlu, Hasan; Gümüşer, Fikriye G

    2011-10-01

    The metabolic comparison of bleomycin (BLM) and bleomycin-glucuronide (BLMG) radiolabeled with (99m)Tc ((99m)Tc-BLM and (99m)Tc-BLMG, respectively) has been investigated in this study. Quality control procedures were carried out using thin-layer radiochromatography and high-performance liquid chromatography. To compare the metabolic behavior of BLM and its glucuronide conjugate radiolabeled with (99m)Tc, scintigraphic, and biodistributional techniques were applied using male New Zealand rabbits and Albino Wistar rats. The results obtained have shown that these compounds were successfully radiolabeled with a labeling yield of about 100%. Maximum uptakes of (99m)Tc-BLM and (99m)Tc-BLMG metabolized as N-glucuronide were observed within 2 hours in the liver, the bladder, and the spinal cord for (99m)Tc-BLM and the lung, the liver, the kidney, the large intestine, and the spinal cord for (99m)Tc-BLMG, respectively. Scintigraphy and biodistributional studies performed on the experimental animals have shown that radiopharmaceutical potentials of these compounds are completely different. At the same time, uptake of the (99m)Tc-BLMG was found to be better than that of (99m)Tc-BLM.

  6. Extensive intestinal glucuronidation of raloxifene in vivo in pigs and impact for oral drug delivery.

    Science.gov (United States)

    Thörn, Helena Anna; Yasin, Mohammed; Dickinson, Paul Alfred; Lennernäs, Hans

    2012-09-01

    In this study an advanced multisampling site pig model, with simultaneous venous blood sampling pre- and post liver, was applied to quantify the role of the intestine in relation to the liver in first-pass glucuronidation of raloxifene in vivo. The pharmacokinetic of raloxifene (a BCS/BDDCS class II compound) in humans is characterized by extensive metabolism (>90%) and the major metabolite is the 4'-β-glucuronide (R-4-G). Following intra-jejunal (i.j.) single dose administration in pigs raloxifene was metabolized in the gut (E(G)) during first-pass to more than 70% and a high concentration (AUC(0-6 h) ratio R-4-G/raloxifene >100) of R-4-G was reached in the portal vein. The hepatic extraction (E(H)) of raloxifene was ~50% and as in humans the bioavailability become low (~7%) in pigs. Interestingly the E(H) of raloxifene and R-4-G was time-dependent after i.j. administration. It is clear that the gut was the dominating organ in first-pass extraction of raloxifene in vivo in pigs. The quantification in this study support earlier human data and emphasize that intestinal glucuronidation should be considered early in the pharmaceutical development.

  7. Vibrational spectroscopic studies of N1-ethyl-5‧-bromo-7-azaindirubin-3‧-oxime and N1-ethyl-indirubin-3‧-monooxime

    Science.gov (United States)

    Li, Ying-Sing; Yao, Qi-Zheng; Wang, Zhao-Hui; Cheng, Jingcai; Truong, Tuyen Thi T.

    2015-05-01

    We have prepared N1-ethyl-5‧-bromo-7-azaindirubin-3‧-oxime due to its potential for being a pharmaceutical. Infrared and Raman spectra have been recorded and vibrational assignments have been suggested based mainly on our previous vibrational investigation of N1-isopropyl-5‧-chloro-7-azaindirubin-3‧-oxime and on group characteristic frequencies. Temperature variation study has revealed the presence of conformers due to the internal rotation of ethyl group. IR spectra collected for N1-ethyl-7-azaindirubin-3‧-oxime have shown rather similar spectral features with that of N1-ethyl-5‧-bromo-7-azaindirubin-3‧-oxime. IR spectra of these compounds have revealed the association through hydrogen bonding in the solid state. IR spectra recorded for these samples after annealing at high temperatures indicated the thermal conversion temperature to be lowered than 270 °C. Results from thermal analyses have determined the beginning decomposition temperatures to be 250 °C and the decomposition enthalpies to be 94 kJ/mol for both N1-ethyl-5‧-bromo-7-azaindirubin-3‧-oxime and N1-ethyl-7-azaindirubin-3‧-oxime.

  8. Hemo-De as substitute for ethyl acetate in formalin-ethyl acetate concentration technique.

    OpenAIRE

    Neimeister, R; Logan, A L; Gerber, B; Egleton, J H; Kleger, B

    1987-01-01

    In comparative studies, Hemo-De (PMP Medical Industries, Inc., Irving, Tex.) was found to be a suitable replacement for ethyl acetate in the Formalin-ethyl acetate concentration technique. With essentially equivalent recovery rates for both procedures, the Formalin-Hemo-De concentration technique is considered to be the preferred technique because Hemo-De is less toxic and less flammable and does not present disposal problems, and its cost is approximately one-fourth that of ethyl acetate.

  9. Optimization and validation of liquid chromatography and headspace-gas chromatography based methods for the quantitative determination of capsaicinoids, salicylic acid, glycol monosalicylate, methyl salicylate, ethyl salicylate, camphor and l-menthol in a topical formulation.

    Science.gov (United States)

    Pauwels, Jochen; D'Autry, Ward; Van den Bossche, Larissa; Dewever, Cédric; Forier, Michel; Vandenwaeyenberg, Stephanie; Wolfs, Kris; Hoogmartens, Jos; Van Schepdael, Ann; Adams, Erwin

    2012-02-23

    Capsaicinoids, salicylic acid, methyl and ethyl salicylate, glycol monosalicylate, camphor and l-menthol are widely used in topical formulations to relieve local pain. For each separate compound or simple mixtures, quantitative analysis methods are reported. However, for a mixture containing all above mentioned active compounds, no assay methods were found. Due to the differing physicochemical characteristics, two methods were developed and optimized simultaneously. The non-volatile capsaicinoids, salicylic acid and glycol monosalicylate were analyzed with liquid chromatography following liquid-liquid extraction, whereas the volatile compounds were analyzed with static headspace-gas chromatography. For the latter method, liquid paraffin was selected as compatible dilution solvent. The optimized methods were validated in terms of specificity, linearity, accuracy and precision in a range of 80% to 120% of the expected concentrations. For both methods, peaks were well separated without interference of other compounds. Linear relationships were demonstrated with R² values higher than 0.996 for all compounds. Accuracy was assessed by performing replicate recovery experiments with spiked blank samples. Mean recovery values were all between 98% and 102%. Precision was checked at three levels: system repeatability, method precision and intermediate precision. Both methods were found to be acceptably precise at all three levels. Finally, the method was successfully applied to the analysis of some real samples (cutaneous sticks). Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Ethylation interference footprinting of DNA-protein complexes.

    Science.gov (United States)

    Manfield, Iain W; Stockley, Peter G

    2009-01-01

    Structural studies of DNA-protein complexes reveal networks of contacts between proteins and the phosphates, sugars and bases of DNA. A range of biochemical methods, termed chemical footprinting, aim to determine the functional groups on DNA which are protected in solution by bound protein against modification or where chemical pre-modification interferes with subsequent protein binding. One of these approaches, termed ethylation interference footprinting, reveals which backbone phosphate groups are contacted by protein and the positions where the DNA-protein interface is so tight that the modification cannot be accommodated. This chapter describes the steps necessary to perform an ethylation interference experiment, including modification of DNA using ethylnitrosourea, fractionation of the products based on their affinities for a DNA-binding protein and analysis of the "bound" and "free" fractions to reveal sites critical for complex formation. This is illustrated using results from our experiments with the Escherichia coli methionine repressor, MetJ.

  11. In vitro evaluation of the effects of anti-fungals, benzodiazepines and non-steroidal anti-inflammatory drugs on the glucuronidation of 19-norandrosterone: implications on doping control analysis.

    Science.gov (United States)

    Palermo, Amelia; Alessi, Beatrice; Botrè, Francesco; de la Torre, Xavier; Fiacco, Ilaria; Mazzarino, Monica

    2016-09-01

    We have studied whether the phase II metabolism of 19-norandrosterone, the most representative metabolite of 19-nortestosterone (nandrolone), can be altered in the presence of other drugs that are not presently included on the Prohibited List of the World Anti-Doping Agency. In detail, we have evaluated the effect of non-prohibited drugs belonging to the classes of anti-fungals, benzodiazepines, and non-steroidal anti-inflammatory drugs on the glucuronidation of 19-norandrosterone. In vitro assays based on the use of either pooled human liver microsomes or specific recombinant isoforms of uridine diphosphoglucuronosyl-transferase were designed and performed to monitor the formation of 19-norandrosterone glucuronide from 19-norandrosterone. Determination of 19-norandrosterone (free and conjugated fraction) was performed by gas chromatography - mass spectrometry after sample pretreatment consisting of an enzymatic hydrolysis (performed only for the conjugated fraction), liquid/liquid extraction with tert-butylmethyl ether, and derivatization to form the trimethylsilyl derivative. In parallel, a method based on reversed-phase liquid chromatography coupled to tandem mass spectrometry in positive electrospray ionization with acquisition in selected reaction monitoring mode was also developed to identify the non-prohibited drugs considered in this study. Incubation experiments have preliminarily shown that the glucuronidation of 19-norandrosterone is principally carried out by UGT2B7 (39%) and UGT2B17 (31%). Inhibition studies have shown that the yield of the glucuronidation reaction is reduced in the presence of the anti-fungals itraconazole, ketoconazole, and miconazole, of the benzodiazepine triazolam and of the non-steroidal anti-inflammatory drugs diclofenac and ibuprofen, while no alteration was recorded in the presence of all other compounds considered in this study. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  12. Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.

    Science.gov (United States)

    Antonilli, Letizia; Togna, Anna Rita; Sabatini, Giovanna; Venditti, Alessandro; Guarcini, Laura; Togna, Giuseppina I; Nicoletti, Rosario; Sanasi, Filomena; Bianco, Armandodoriano; Nencini, Paolo

    2013-12-15

    We have previously found that phenanthrenic opioids, including codeine, modulate morphine glucuronidation in the rat. Here codeine and five of its derivatives were compared in their effects on the synthesis of morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) from morphine by rat liver microsomal preparations, and by primary cultures of rat hepatocytes previously incubated for 72 h with either codeine or its derivatives. Acetylcodeine and pivaloylcodeine shared the capability of the parent compound of inhibiting the synthesis of M3G by liver microsomes through a noncompetitive mechanism of action. Their IC50 were 3.25, 2.27, and 4.32 μM, respectively. Dihydrocodeine, acetyldihydrocodeine, and lauroylcodeine were ineffective. In all the experimental circumstances M6G was undetectable in the incubation medium. In primary hepatocyte cultures codeine only inhibited M3G formation, but with a lower efficacy than that observed with microsomes (IC50 20.91 vs 4.32 μM). Preliminary results show that at micromolar concentrations codeine derivatives exhibit a low rate of affinity for μ opiate receptors. In conclusion, acetyl and pivaloyl derivatives of codeine noncompetitively inhibit liver glucuronidation of morphine interacting with microsomes. This study further strengths the notion that phenanthrenic opioids can modulate morphine glucuronidation independently from their effects on μ opiate receptors. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Sensitive, automatic method for the determination of diazepam and its five metabolites in human oral fluid by online solid-phase extraction and liquid chromatography with tandem mass spectrometry

    DEFF Research Database (Denmark)

    Jiang, Fengli; Rao, Yulan; Wang, Rong

    2016-01-01

    A novel and simple online solid-phase extraction liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of diazepam and its five metabolites including nordazepam, oxazepam, temazepam, oxazepam glucuronide, and temazepam glucuronide...... consuming a single oral dose of 10 mg diazepam were analyzed to demonstrate the applicability of this method....

  14. Milk Thistle Constituents Inhibit Raloxifene Intestinal Glucuronidation: A Potential Clinically Relevant Natural Product-Drug Interaction.

    Science.gov (United States)

    Gufford, Brandon T; Chen, Gang; Vergara, Ana G; Lazarus, Philip; Oberlies, Nicholas H; Paine, Mary F

    2015-09-01

    Women at high risk of developing breast cancer are prescribed selective estrogen response modulators, including raloxifene, as chemoprevention. Patients often seek complementary and alternative treatment modalities, including herbal products, to supplement prescribed medications. Milk thistle preparations, including silibinin and silymarin, are top-selling herbal products that may be consumed by women taking raloxifene, which undergoes extensive first-pass glucuronidation in the intestine. Key constituents in milk thistle, flavonolignans, were previously shown to be potent inhibitors of intestinal UDP-glucuronosyl transferases (UGTs), with IC50s ≤ 10 μM. Taken together, milk thistle preparations may perpetrate unwanted interactions with raloxifene. The objective of this work was to evaluate the inhibitory effects of individual milk thistle constituents on the intestinal glucuronidation of raloxifene using human intestinal microsomes and human embryonic kidney cell lysates overexpressing UGT1A1, UGT1A8, and UGT1A10, isoforms highly expressed in the intestine that are critical to raloxifene clearance. The flavonolignans silybin A and silybin B were potent inhibitors of both raloxifene 4'- and 6-glucuronidation in all enzyme systems. The Kis (human intestinal microsomes, 27-66 µM; UGT1A1, 3.2-8.3 µM; UGT1A8, 19-73 µM; and UGT1A10, 65-120 µM) encompassed reported intestinal tissue concentrations (20-310 µM), prompting prediction of clinical interaction risk using a mechanistic static model. Silibinin and silymarin were predicted to increase raloxifene systemic exposure by 4- to 5-fold, indicating high interaction risk that merits further evaluation. This systematic investigation of the potential interaction between a widely used herbal product and chemopreventive agent underscores the importance of understanding natural product-drug interactions in the context of cancer prevention. Copyright © 2015 by The American Society for Pharmacology and Experimental

  15. Glucuronidated Quercetin Lowers Blood Pressure in Spontaneously Hypertensive Rats via Deconjugation

    Science.gov (United States)

    Galindo, Pilar; Rodriguez-Gómez, Isabel; González-Manzano, Susana; Dueñas, Montserrat; Jiménez, Rosario; Menéndez, Carmen; Vargas, Félix; Tamargo, Juan; Santos-Buelga, Celestino; Pérez-Vizcaíno, Francisco; Duarte, Juan

    2012-01-01

    Background Chronic oral quercetin reduces blood pressure and restores endothelial dysfunction in hypertensive animals. However, quercetin (aglycone) is usually not present in plasma, because it is rapidly metabolized into conjugated, mostly inactive, metabolites. The aim of the study is to analyze whether deconjugation of these metabolites is involved in the blood pressure lowering effect of quercetin. Methodology/Principal Findings We have analyzed the effects on blood pressure and vascular function in vitro of the conjugated metabolites of quercetin (quercetin-3-glucuronide, Q3GA; isorhamnetin-3-glucuronide, I3GA; and quercetin-3′-sulfate, Q3'S) in spontaneously hypertensive rats (SHR). Q3GA and I3GA (1 mg/kg i.v.), but not Q3'S, progressively reduced mean blood pressure (MBP), measured in conscious SHR. The hypotensive effect of Q3GA was abolished in SHR treated with the specific inhibitor of β-glucuronidase, saccharic acid 1,4-lactone (SAL, 10 mg/ml). In mesenteric arteries, unlike quercetin, Q3GA had no inhibitory effect in the contractile response to phenylephrine after 30 min of incubation. However, after 1 hour of incubation Q3GA strongly reduced this contractile response and this effect was prevented by SAL. Oral administration of quercetin (10 mg/Kg) induced a progressive decrease in MBP, which was also suppressed by SAL. Conclusions Conjugated metabolites are involved in the in vivo antihypertensive effect of quercetin, acting as molecules for the plasmatic transport of quercetin to the target tissues. Quercetin released from its glucuronidated metabolites could be responsible for its vasorelaxant and hypotensive effect. PMID:22427863

  16. Milk Thistle Constituents Inhibit Raloxifene Intestinal Glucuronidation: A Potential Clinically Relevant Natural Product–Drug Interaction

    Science.gov (United States)

    Gufford, Brandon T.; Chen, Gang; Vergara, Ana G.; Lazarus, Philip; Oberlies, Nicholas H.

    2015-01-01

    Women at high risk of developing breast cancer are prescribed selective estrogen response modulators, including raloxifene, as chemoprevention. Patients often seek complementary and alternative treatment modalities, including herbal products, to supplement prescribed medications. Milk thistle preparations, including silibinin and silymarin, are top-selling herbal products that may be consumed by women taking raloxifene, which undergoes extensive first-pass glucuronidation in the intestine. Key constituents in milk thistle, flavonolignans, were previously shown to be potent inhibitors of intestinal UDP-glucuronosyl transferases (UGTs), with IC50s ≤ 10 μM. Taken together, milk thistle preparations may perpetrate unwanted interactions with raloxifene. The objective of this work was to evaluate the inhibitory effects of individual milk thistle constituents on the intestinal glucuronidation of raloxifene using human intestinal microsomes and human embryonic kidney cell lysates overexpressing UGT1A1, UGT1A8, and UGT1A10, isoforms highly expressed in the intestine that are critical to raloxifene clearance. The flavonolignans silybin A and silybin B were potent inhibitors of both raloxifene 4′- and 6-glucuronidation in all enzyme systems. The Kis (human intestinal microsomes, 27–66 µM; UGT1A1, 3.2–8.3 µM; UGT1A8, 19–73 µM; and UGT1A10, 65–120 µM) encompassed reported intestinal tissue concentrations (20–310 µM), prompting prediction of clinical interaction risk using a mechanistic static model. Silibinin and silymarin were predicted to increase raloxifene systemic exposure by 4- to 5-fold, indicating high interaction risk that merits further evaluation. This systematic investigation of the potential interaction between a widely used herbal product and chemopreventive agent underscores the importance of understanding natural product–drug interactions in the context of cancer prevention. PMID:26070840

  17. Lack of glucuronidation products of trans-resveratrol in plasma and urine of cats.

    Science.gov (United States)

    Burnett, K; Puschner, B; Ramsey, J J; Lin, Y; Wei, A; Fascetti, A J

    2017-04-01

    Resveratrol has generated interest in cats due to reported health benefits. Cats have low activity of β-glucuronidase, and we hypothesized they could not form two common resveratrol metabolites, resveratrol-3-O-glucuronide and resveratrol-4'-O-glucuronide. Resveratrol, 3 mg/cat/day, was given orally to intact male (n = 5) and female cats (n = 5) for 4 weeks. A control group (8 intact males) was used for comparison. Plasma and urine were collected weekly and analysed using high-pressure liquid chromatography coupled with tandem mass spectrometry. Resveratrol and resveratrol-3-O-sulphate, but no glucuronide metabolites, were detected in plasma and urine. Median (range 10-90th percentile) plasma resveratrol for control and treatment groups was 0.46 ng/ml (0.02-1.74 ng/ml) and 0.96 ng/ml (0.65-3.21 ng/ml). Median (range) plasma resveratrol-3-O-sulphate for control and treatment groups was 6.32 ng/ml (2.55-10.29 ng/ml) and 11.45 ng/ml (1.47-53.29 ng/ml). Plasma resveratrol differed from control in week 4, while plasma resveratrol-3-O-sulphate was different in all weeks (p urine resveratrol for control and treatment groups was 0.28 ng/ml (0.05-1.59 ng/ml) and 19.98 ng/ml (8.44-87.54 ng/ml). Median (range) urine resveratrol-3-O-sulphate for control and treatment groups was 26.71 ng/ml (10.50-75.58 ng/ml) and 108.69 ng/ml (11.83-231.05 ng/ml). All time points for urine resveratrol and resveratrol-3-O-sulphate were significantly different from control (p cats are unlikely able to glucuronidate resveratrol, most likely due to a reduction in the activity of β-glucuronidase. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

  18. Is THC-COOH-glucuronide a useful marker for Tetrahydrocannabinol (THC) in DUID cases?

    DEFF Research Database (Denmark)

    Telving, Rasmus; Hasselstrøm, Jørgen Bo; Andreasen, Mette Findal

    ). Introduction The physical and chemical nature of THC makes it difficult to include in traditional screening procedures along with other common legal and illegal drugs. Development of multi-component toxicological screening procedures that include THC is therefore a challenge but also highly desirable in high...... from Bruker. The Screening for THC-COOH-glucuronide included 1608 DUID whole blood samples from 2013 and 2014 already quantified on an existing validated LC-MS/MS method using Multiple Reaction Monitoring (MRM). The Danish per se limit for THC in DUID cases is 1.0 µg/kg blood and to compensate...

  19. Rapid quantification of free and glucuronidated THCCOOH in urine using coated well plates and LC-MS/MS analysis.

    Science.gov (United States)

    Hädener, Marianne; Weinmann, Wolfgang; van Staveren, Dave R; König, Stefan

    2017-03-01

    Generally, urine drug testing for cannabis abuse involves measuring total concentrations of 11-nor-9-carboxy-Δ 9 -tetrahydrocannabinol (THCCOOH) obtained by enzymatic and/or alkaline hydrolysis of THCCOOH-glucuronide. As hydrolysis can be inconsistent and incomplete, direct measurement of the two metabolites is preferable. Methodology & results: We developed a high-throughput LC-MS/MS method for simultaneous quantification of free and glucuronidated THCCOOH in urine using coated 96-well plates for analyte extraction and column-switching chromatography. Excellent separation of the two analytes was achieved within 2.5 min, with linear ranges from 5 to 2000 μg/l for THCCOOH and from 10 to 4000 μg/l for THCCOOH-glucuronide. The method was successfully validated and applied to authentic urine samples from cannabis consumers, demonstrating its applicability for routine cannabinoid testing.

  20. Behaviour of solid phase ethyl cyanide in simulated conditions of Titan

    Science.gov (United States)

    Couturier-Tamburelli, I.; Toumi, A.; Piétri, N.; Chiavassa, T.

    2018-01-01

    In order to simulate different altitudes in the atmosphere of Titan, we investigated using infrared spectrometry and mass spectrometry the photochemistry of ethyl cyanide (CH3CH2CN) ices at different temperatures. Heating experiments of the solid phase until complete desorption showed up three phase transitions with a first one appearing to be approximately at the temperature of Titan's surface (94 K), measured by the Huygens probe. Ethyl cyanide, whose presence has been suggested in solid phase in Titan, can be considered as another nitrile for photochemical models of the Titan atmosphere after our first study (Toumi et al., 2016) concerning vinyl cyanide (CH2CHCN). The desorption energy of ethyl cyanide has been calculated to be 36.75 ( ± 0.55) kJ mol-1 using IRTF and mass spectroscopical techniques. High energetic photolysis (λ > 120 nm) have been performed and we identified ethyl isocyanide, vinyl cyanide, cyanoacetylene, ethylene, acetylene, cyanhydric acid and a methylketenimine form as photoproducts from ethyl cyanide. The branching ratios of the primary products were determined at characteristic temperatures of Titan thanks to the value of the νCN stretching band strength of ethyl cyanide that has been calculated to be 4.12 × 10-18 cm molecule-1. We also report here for the first time the values of the photodissociation cross sections of C2H5CN for different temperatures.

  1. Topical ethyl chloride fine spray. Does it have any antimicrobial activity?

    Energy Technology Data Exchange (ETDEWEB)

    Burney, K.; Bowker, K.; Reynolds, R.; Bradley, M

    2006-12-15

    Aim: The aim of this study was to assess whether ethyl chloride fine spray (Cryogesic[reg]) has antimicrobial activity. Material and methods: Blood agar plates supplemented with 5% horse blood were inoculated with five different organisms, coagulase-negative staphylococci (CNS), methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), Streptococcus pyogenes and Enterococcus faecalis. The plates were assessed for growth inhibition at 24 and 48 h by the microbiologist and compared with the non-sprayed control plates. Results: The model showed a highly significant (p < 0.0001) reduction in bacterial count for the plates treated with fine ethyl chloride spray. The estimate of the percentage of bacteria remaining after spraying with ethyl chloride was 42.7%, with a 95% confidence interval of 35.9-50.9%. There was no evidence that the effect of ethyl chloride fine spray was different for the different organisms (p = 0.49). Conclusion: The use of ethyl chloride shows bacterial count reduction but the clinical implication of this needs to be determined. The authors postulate that any statistically significant reduction can only be helpful in reducing the infection rates. This coupled with the already proven local anaesthetic effects of ethyl chloride will make it an important tool for procedures like arthrocentesis and venepunctures.

  2. 2-Ethyl-3,5,6-triphenylpyrazine

    Directory of Open Access Journals (Sweden)

    N. Anuradha

    2012-10-01

    Full Text Available In the title molecule, C24H20N2, the pyrazine ring is significantly distorted from planarity, presumably due to steric crowding, and its conformation is well described as a flattened twist-boat. The benzene ring adjacent to the ethyl group forms dihedral angles of 53.79 (13 and 85.47 (12° with the other benzene rings; the dihedral angle between adjacent benzene rings is 57.90 (12°. The ethyl group is disordered over two positions; the site-occupancy factor of the major component is 0.546 (4. No hydrogen bonds are found in the crystal structure.

  3. Interaction of hesperetin glucuronide conjugates with human BCRP, MRP2 and MRP3 as detected in membrane vesicles of overexpressing baculovirus-infected Sf9 cells

    NARCIS (Netherlands)

    Brand, W.; Oosterhuis, B.; Krajcsi, P.; Barron, D.; Dionisi, F.; Bladeren, van P.J.; Rietjens, I.; Williamson, G.

    2011-01-01

    The citrus flavonoid hesperetin (4'-methoxy-3',5,7-trihydroxyflavanone) is the aglycone of hesperidin, the major flavonoid present in sweet oranges. Hesperetin 7-O-glucuronide (H7G) and hesperetin 3'-O-glucuronide (H3'G) are the two most abundant metabolites of hesperetin in vivo. In this study,

  4. Neuroexcitatory effects of morphine-3-glucuronide are dependent on Toll-like receptor 4 signaling

    Directory of Open Access Journals (Sweden)

    Due Michael R

    2012-08-01

    Full Text Available Abstract Background Multiple adverse events are associated with the use of morphine for the treatment of chronic non-cancer pain, including opioid-induced hyperalgesia (OIH. Mechanisms of OIH are independent of opioid tolerance and may involve the morphine metabolite morphine-3-glucuronide (M3G. M3G exhibits limited affinity for opioid receptors and no analgesic effect. Previous reports suggest that M3G can act via the Toll-like receptor 4 (TLR4/myeloid differentiation protein-2 (MD-2 heterodimer in the central nervous system to elicit pain. Methods Immunoblot and immunocytochemistry methods were used to characterize the protein expression of TLR4 present in lumbar dorsal root ganglion (DRG. Using in vitro intracellular calcium and current clamp techniques, we determined whether TLR4 activation as elicited by the prototypical agonists of TLR4, lipopolysaccharide (LPS and M3G, contributed to changes in intracellular calcium and increased excitation. Rodents were also injected with M3G to determine the degree to which M3G-induced tactile hyperalgesia could be diminished using either a small molecule inhibitor of the MD-2/TLR4 complex in rats or TLR4 knockout mice. Whole cell voltage-clamp recordings were made from small- and medium-diameter DRG neurons (25 μm  Results We observed that TLR4 immunoreactivity was present in peptidergic and non-peptidergic sensory neurons in the DRG. Non-neuronal cells in the DRG lacked evidence of TLR4 expression. Approximately 15% of assayed small- and medium-diameter sensory neurons exhibited a change in intracellular calcium following LPS administration. Both nociceptive and non-nociceptive neurons were observed to respond, and approximately 40% of these cells were capsaicin-insensitive. Increased excitability observed in sensory neurons following LPS or M3G could be eliminated using Compound 15, a small molecule inhibitor of the TLR4/MD-2 complex. Likewise, systemic injection of M3G induced rapid tactile, but

  5. Exposure assessment and risk characterisation of ethyl carbamate from Korean traditional fermented rice wine, Takju and Yakju.

    Science.gov (United States)

    Lee, Joon-Goo; Park, Sung-Kug; Yoon, Hae-Jung; Kang, Dong-Hyun; Kim, Meehye

    2016-01-01

    Ethyl carbamate is one of the most hazardous chemicals naturally occurring in food, and is present in alcoholic beverages. Korean traditional rice wine, Takju and Yakju, is frequently consumed in Korea, but there have been no studies characterising the risks of ethyl carbamate in these products. In order to assess and characterise the exposure risk of ethyl carbamate in Korean traditional rice wines, ethyl carbamate was investigated by means of GC-MS. The analytical methods were optimised and validated through determining linearity, detection limit, quantification limit, recovery and precision. A total of 283 traditional Korean rice wines, including 175 Takju and 108 Yakju samples, were analysed. Exposure assessment was performed by factoring in ethyl carbamate content, daily consumption and body weight. Daily exposures of ethyl carbamate were estimated for adults in four age groups, and risks of ethyl carbamate were characterised by the margin of exposure, which is more than 10 000. Based on this study, the risks of ethyl carbamate in Korean traditional rice wine were shown to be of low concern.

  6. Solid acid catalysed formation of ethyl levulinate and ethyl glucopyranoside from mono- and disaccharides

    DEFF Research Database (Denmark)

    Shunmugavel, Saravanamurugan; Riisager, Anders

    2012-01-01

    Sulfonic acid functionalised SBA-15 (SO3H-SBA-15), sulfated zirconia and beta, Y, ZSM-5 and mordenite zeolite catalysts have been applied for the dehydration of sugars to ethyl levulinate and ethyl-D-glucopyranoside (EDGP) using ethanol as solvent and reactant. The SO3H-SBA-15 catalyst showed...... a high catalytic activity for the selective conversion of fructose to ethyl levulinate (57%) and glucose to EDGP (80%) at 140 °C, whereas the disaccharide sucrose yielded a significant amount of both products. The SO3H-SBA-15 catalysts were found to be highly active compared to the zeolites under...

  7. Vapour pressures and osmotic coefficients of binary mixtures of 1-ethyl-3-methylimidazolium ethylsulfate and 1-ethyl-3-methylpyridinium ethylsulfate with alcohols at T = 323.15 K

    Energy Technology Data Exchange (ETDEWEB)

    Calvar, Noelia [Laboratory of Separation and Reaction Engineering, Departamento de Engenharia Quimica, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, 4200-465 Porto (Portugal); Gonzalez, Begona; Dominguez, Angeles [Departamento de Ingenieria Quimica, Universidad de Vigo, 36200 Vigo (Spain); Macedo, Eugenia A. [Laboratory of Separation and Reaction Engineering, Departamento de Engenharia Quimica, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, 4200-465 Porto (Portugal)], E-mail: eamacedo@fe.up.pt

    2009-12-15

    Osmotic coefficients of binary mixtures containing alcohols (ethanol, 1-propanol, and 2-propanol) and the ionic liquids 1-ethyl-3-methylimidazolium ethylsulfate and 1-ethyl-3-methylpyridinium ethylsulfate were determined at T = 323.15 K. Vapour pressure and activity coefficients of the studied systems were calculated from experimental data. The extended Pitzer model modified by Archer, and the modified NRTL model (MNRTL) were used to correlate the experimental data, obtaining standard deviations lower than 0.012 and 0.031, respectively. The mean molal activity coefficients and the excess Gibbs free energy of the studied binary mixtures were calculated from the parameters obtained with the extended Pitzer model of Archer.

  8. 2-Ethyl-6-methylanilinium 4-methylbenzenesulfonate

    Directory of Open Access Journals (Sweden)

    Jiao Ye

    2009-02-01

    Full Text Available The title compound, C9H14N+·C7H7SO3−, contains a 2-ethyl-6-methylanilinium cation and a 4-methylbenzenesulfonic anion. The cations are anchored between the anions through N—H...O hydrogen bonds. Electrostatic and van der Waals interactions, as well as hydrogen bonds, maintain the structural cohesion.

  9. Manufacturing Ethyl Acetate From Fermentation Ethanol

    Science.gov (United States)

    Rohatgi, Naresh K.; Ingham, John D.

    1991-01-01

    Conceptual process uses dilute product of fermentation instead of concentrated ethanol. Low-concentration ethanol, extracted by vacuum from fermentation tank, and acetic acid constitutes feedstock for catalytic reaction. Product of reaction goes through steps that increases ethyl acetate content to 93 percent by weight. To conserve energy, heat exchangers recycle waste heat to preheat process streams at various points.

  10. 77 FR 12740 - Trinexapac-ethyl; Pesticide Tolerances

    Science.gov (United States)

    2012-03-02

    ... AGENCY 40 CFR Part 180 Trinexapac-ethyl; Pesticide Tolerances AGENCY: Environmental Protection Agency... plant growth regulator, trinexapac-ethyl and its primary metabolite CGA-179500, in or on grass, forage... aggregate exposure for trinexapac-ethyl including exposure resulting from the tolerances established by this...

  11. 77 FR 60917 - Trinexapac-ethyl; Pesticide Tolerances

    Science.gov (United States)

    2012-10-05

    ... AGENCY 40 CFR Part 180 RIN 2070-ZA16 Trinexapac-ethyl; Pesticide Tolerances AGENCY: Environmental... trinexapac-ethyl in or on multiple commodities and modifies existing tolerance levels and commodity definitions for trinexapac-ethyl, which are identified and discussed later in this document. EPA proposed...

  12. Supercritical antisolvent co-precipitation of rifampicin and ethyl cellulose

    CSIR Research Space (South Africa)

    Djerafi, R

    2017-05-01

    Full Text Available Rifampicin-loaded submicron-sized particles were prepared through supercritical anti-solvent process using ethyl cellulose as polymeric encapsulating excipient. Ethyl acetate and a mixture of ethyl acetate/dimethyl sulfoxide (70/30 and 85/15) were...

  13. 77 FR 41346 - Trinexapac-ethyl; Proposed Pesticide Tolerance

    Science.gov (United States)

    2012-07-13

    ... AGENCY 40 CFR Part 180 Trinexapac-ethyl; Proposed Pesticide Tolerance AGENCY: Environmental Protection... FFDCA section 408(e), 21 U.S.C. 346a(e), is proposing to amend the existing trinexapac-ethyl tolerances... tolerance table for trinexapac-ethyl that was published in the Federal Register on March 2, 2012 (77 FR...

  14. 21 CFR 177.1320 - Ethylene-ethyl acrylate copolymers.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethylene-ethyl acrylate copolymers. 177.1320... Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1320 Ethylene-ethyl acrylate copolymers. Ethylene-ethyl acrylate copolymers may be safely used to produce packaging materials, containers...

  15. 46 CFR 151.50-42 - Ethyl ether.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Ethyl ether. 151.50-42 Section 151.50-42 Shipping COAST... LIQUID HAZARDOUS MATERIAL CARGOES Special Requirements § 151.50-42 Ethyl ether. (a)(1) Gravity tanks... liquid. (g) Precautions shall be taken to prevent the contamination of ethyl ether by strong oxidizing...

  16. Perylenetetracarboxylic diimide (PTCDI) nanowires for sensing ethyl acetate in wine.

    Science.gov (United States)

    Khopkar, Yashdeep; Kojtari, Arben; Swearer, Dayne; Zivanovic, Sandra; Ji, Hai-Feng

    2014-09-01

    We report the application of perylenetetracarboxylic diimide (PTCDI) nanowires for sensing ethyl acetate. The conductivity of the crystalline nano/microwires increases quickly and selectively in the presence of ethyl acetate vapor, but not with water, acid and alcohol vapors, suggesting that the nanowires of PTCDI may be used for monitoring ethyl acetate during a wine manufacturing process.

  17. Liquid chromatographic-mass spectrometric analysis of glucuronide-conjugated anabolic steroid metabolites: method validation and interlaboratory comparison

    NARCIS (Netherlands)

    Hintikka, L.; Kuuranne, T.; Leinonen, A.; Thevis, M.; Schanzer, W.; Halket, J.; Cowan, D.; Grosse, J.; Hemmersbach, P.; Nielen, M.W.F.; Kostiainen, R.

    2008-01-01

    Liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method for simultaneous and direct detection of 12 glucuronide-conjugated anabolic androgenic steroid (AAS) metabolites in human urine is described. The compounds selected were the main metabolites detected in

  18. High-Throughput LC-MS/MS Method for Direct Quantification of Glucuronidated, Sulfated and Free Enterolactone in Human Plasma

    DEFF Research Database (Denmark)

    Nørskov, Natalja; Kyrø, Cecilie; Olsen, Anja

    2016-01-01

    Sulfation and glucuronidation constitute a major pathway in humans and may play an important role in biological activity of metabolites including the enterolignan, enterolactone. Because the aromatic structure of enterolactone has similarities to steroid metabolites, it was hypothesized that ente......Sulfation and glucuronidation constitute a major pathway in humans and may play an important role in biological activity of metabolites including the enterolignan, enterolactone. Because the aromatic structure of enterolactone has similarities to steroid metabolites, it was hypothesized......−MS/MS and a fluoroimmunoassay; however, most of these methods measure the total concentration of enterolactone, without any specification of its conjugation pattern. Here for the first time we present a high-throughput LC−MS/MS method to quantify enterolactone in its intact form as glucuronide, sulfate, and free enterolactone....... The method has shown good accuracy and precision at low concentration and very high sensitivity, with LLOQ for enterolactone sulfate at 16 pM, enterolactone glucuronide at 26 pM, and free enterolactone at 86 pM. The short run time of 2.6 min combined with simple sample clean up and high sensitivity make...

  19. A MONOCLONAL ANTIBODY-BETA-GLUCURONIDASE CONJUGATE AS ACTIVATOR OF THE PRODRUG EPIRUBICIN-GLUCURONIDE FOR SPECIFIC TREATMENT OF CANCER

    NARCIS (Netherlands)

    Haisma, Hidde; BOVEN, E; VANMUIJEN, M; DEJONG, J; VANDERVIJGH, WJF; PINEDO, HM

    The anti-pan carcinoma monoclonal antibody (MAb) 323/A3, linked to E. coli-derived beta-glucuronidase (GUS) was used to study the tumour-site-selective activation of the prodrug Epirubicin-glucuronide (Epi-glu). Epi-glu was isolated from the urine of patients treated with Epirubicin (Epi) by

  20. An ethyl acetate sensor utilizing cataluminescence on Y₂O₃ nanoparticles.

    Science.gov (United States)

    Cao, Xiaoan; Tao, Ying; Li, Liling; Liu, Yonghui; Peng, Yan; Li, Jinwen

    2011-01-01

    A cataluminescence (CTL) sensor using Y₂O₃ nanoparticles as the sensing materials was proposed for the determination of ethyl acetate. This ethyl acetate sensor showed high sensitivity and specificity at the optimal temperature of 264°C. Quantitative analysis was performed at a wavelength of 425 nm. The linear ranges of CTL intensity vs ethyl acetate concentrations were 2.0-250 ppm (r = 0.9965) and 250-6500 ppm (r = 0.9997) with a detection limit (3σ) of 0.5 ppm. There was no response or weak response when foreign substances such as formic acid, n-hexane, toluene, acetic acid, benzene, and formaldehyde passing through the surface of Y₂O₃ nanoparticles. The sensor had a long lifetime more than 80 h with 3600 ppm ethyl acetate. It had been applied successfully to determine ethyl acetate in artificial air samples. Copyright © 2009 John Wiley & Sons, Ltd.

  1. Antihyperglycemic effect of Hypericum perforatum ethyl acetate extract on streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Arokiyaraj, S; Balamurugan, R; Augustian, P

    2011-10-01

    To evaluate the antihyperglycemic activity of ethyl acetate extract of Hypericum perforatum (H. perforatum) in streptozotocin (STZ)-induced diabetic rats. Acute toxicity and oral glucose tolerance test were performed in normal rats. Male albino rats were rendered diabetic by STZ (40 mg/kg, intraperitoneally). H. perforatum ethyl acetate extract was orally administered to diabetic rats at 50, 100 and 200 mg/kg doses for 15 days to determine the antihyperglycemic activity. Biochemical parameters were determined at the end of the treatment. H. perforatum ethyl acetate extract showed dose dependant fall in fasting blood glucose (FBG). After 30 min of extract administration, FBG was reduced significantly when compared with normal rats. H. perforatum ethyl acetate extract produced significant reduction in plasma glucose level, serum total cholesterol, triglycerides, glucose-6-phosphatase levels. Tissue glycogen content, HDL-cholesterol, glucose-6-phosphate dehydrogenase were significantly increased compared with diabetic control. No death or lethal effect was observed in the toxic study. The results demonstrate that H. perforatum ethyl acetate extract possesses potent antihyperglycemic activity in STZ induced diabetic rats.

  2. Fate of 2-Chloro Ethyl Ethyl Sulfide on 13X Molecular Sieve Adsorbent Implications for Regenerative Filtration

    Science.gov (United States)

    2003-11-17

    Fate of 2-Chloro Ethyl Ethyl Sulfide on 13X Molecular Sieve Adsorbent Implications for Regenerative Filtration 2003 Joint Scientific Conference on...2003 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Fate of 2-Chloro Ethyl Ethyl Sulfide on 13X Molecular Sieve Adsorbent...protection than the currently fielded single pass filtration technology. • Many past and current regenerative filtration prototypes utilize zeolite

  3. In Vitro Enhancement of Carvedilol Glucuronidation by Amiodarone-Mediated Altered Protein Binding in Incubation Mixture of Human Liver Microsomes with Bovine Serum Albumin.

    Science.gov (United States)

    Sekimoto, Makoto; Takamori, Toru; Nakamura, Saki; Taguchi, Masato

    2016-01-01

    Carvedilol is mainly metabolized in the liver to O-glucuronide (O-Glu). We previously found that the glucuronidation activity of racemic carvedilol in pooled human liver microsomes (HLM) was increased, R-selectively, in the presence of amiodarone. The aim of this study was to clarify the mechanisms for the enhancing effect of amiodarone on R- and S-carvedilol glucuronidation. We evaluated O-Glu formation of R- and S-carvedilol enantiomers in a reaction mixture of HLM including 0.2% bovine serum albumin (BSA). In the absence of amiodarone, glucuronidation activity of R- and S-carvedilol for 25 min was 0.026, and 0.51 pmol/min/mg protein, and that was increased by 6.15 and 1.60-fold in the presence of 50 µM amiodarone, respectively. On the other hand, in the absence of BSA, or when BSA was replaced with human serum albumin, no enhancing effect of amiodarone on glucuronidation activity was observed, suggesting that BSA played a role in the mechanisms for the enhancement of glucuronidation activity. Unbound fraction of S-carvedilol in the reaction mixture was greater than that of R-carvedilol in the absence of amiodarone. Also, the addition of amiodarone caused a greater increase of unbound fraction of R-carvedilol than that of S-carvedilol. These results suggest that the altered protein binding by amiodarone is a key mechanism for R-selective stimulation of carvedilol glucuronidation.

  4. Quantitative profiling of human renal UDP-glucuronosyltransferases and glucuronidation activity: a comparison of normal and tumoral kidney tissues.

    Science.gov (United States)

    Margaillan, Guillaume; Rouleau, Michèle; Fallon, John K; Caron, Patrick; Villeneuve, Lyne; Turcotte, Véronique; Smith, Philip C; Joy, Melanie S; Guillemette, Chantal

    2015-04-01

    Renal metabolism by UDP-glucuronosyltransferase (UGT) enzymes is central to the clearance of many drugs. However, significant discrepancies about the relative abundance and activity of individual UGT enzymes in the normal kidney prevail among reports, whereas glucuronidation in tumoral kidney has not been examined. In this study, we performed an extensive profiling of glucuronidation metabolism in normal (n = 12) and tumor (n = 14) kidneys using targeted mass spectrometry quantification of human UGTs. We then correlated UGT protein concentrations with mRNA levels assessed by quantitative polymerase chain reaction and with conjugation activity for the major renal UGTs. Beyond the wide interindividual variability in expression levels observed among kidney samples, UGT1A9, UGT2B7, and UGT1A6 are the most abundant renal UGTs in both normal and tumoral tissues based on protein quantification. In normal kidney tissues, only UGT1A9 protein levels correlated with mRNA levels, whereas UGT1A6, UGT1A9, and UGT2B7 quantification correlated significantly with their mRNA levels in tumor kidneys. Data support that posttranscriptional regulation of UGT2B7 and UGT1A6 expression is modulating glucuronidation in the kidney. Importantly, our study reveals a significant decreased glucuronidation capacity of neoplastic kidneys versus normal kidneys that is paralleled by drastically reduced UGT1A9 and UGT2B7 mRNA and protein expression. UGT2B7 activity is the most repressed in tumors relative to normal tissues, with a 96-fold decrease in zidovudine metabolism, whereas propofol and sorafenib glucuronidation is decreased by 7.6- and 5.2-fold, respectively. Findings demonstrate that renal drug metabolism is predominantly mediated by UGT1A9 and UGT2B7 and is greatly reduced in kidney tumors. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  5. Antioxidative Flavonol Glucuronides and Anti-HBsAg Flavonol from Rotala rotundifolia

    Directory of Open Access Journals (Sweden)

    Li-Jie Zhang

    2011-10-01

    Full Text Available Two new flavonol glucuronides, quercetin 3-O-β-d-2″-acetylglucuronide (1 and quercetin 3-O-β-d-2″-acetylglucuronide methyl ester (2, along with four known flavonoids (3-6 were isolated from the whole parts of Rotala rotundifolia. The structures of 1 and 2 were elucidated by application of various spectroscopic methods, including 1D and 2D NMR techniques. Biological evaluation showed that all of isolated flavonoid compounds have potent anti-oxidative activities by DPPH and superoxide anion methods, and kaempferol (3 and quercetin (4 exhibited significant anti-HBV activity assayed by anti-HBsAg production. The HPLC fingerprint with photodiode array detection (HPLC-DAD for quality control of R. rotundifolia partitioned EtOAc layer was also established.

  6. Bioavailability of {sup 99m}Tc-paclitaxel-glucuronide ({sup 99m}Tc-PAC-G)

    Energy Technology Data Exchange (ETDEWEB)

    Biber Muftuler, F.Z.; Demir, I.; Uenack, P.; Ichedef, C.; Yurt Kilcar, A. [Ege Univ., Izmir (Turkey). Dept. of Nuclear Applications

    2011-07-01

    An antitumor agent paclitaxel (PAC) has been proved to be efficient in the treatment of breast and ovarian cancer. Glucuronic acid-derived paclitaxel compound (paclitaxel-glucuronide (PAC-G)) was enzymatically synthesized using microsome preparate separated from rat livers. The biodistribution mechanism of PAC-G in healthy female Albino Wistar rats has been investigated. The expected structure is confirmed according to LC/MS results, and the possible attachment is to C2-hydroxyl group. PAC-G was labeled with {sup 99m}Tc and the radiochemical yield of radiolabeled compound ({sup 99m}Tc-PAC-G) was 98.0 {+-} 02.74% (n=9). The range of the breast/blood and breast/muscle ratios is approximately between 3 and 35 in 240 min. All these experimental studies indicate that {sup 99m}Tc-PAC-G may potentially be used in breast tissue as an imaging agent. (orig.)

  7. UHPLC-MS/MS quantification of buprenorphine, norbuprenorphine, methadone, and glucuronide conjugates in umbilical cord plasma.

    Science.gov (United States)

    Kyle, Amy Redmond; Carmical, Jennifer; Shah, Darshan; Pryor, Jason; Brown, Stacy

    2015-10-01

    Opioid use during pregnancy can result in the newborn being physically dependent on the substance, thus experiencing drug withdrawal, termed neonatal abstinence syndrome (NAS). Buprenorphine and methadone are two drugs used to treat opioid withdrawal and are approved for use in pregnancy. Quantification of these compounds in umbilical cord plasma would help assess in utero exposure of neonates in cases of buprenorphine or methadone use during pregnancy. An LC-MS/MS method using solid-phase extraction sample preparation was developed and validated for the simultaneous quantification of methadone, buprenorphine, norbuprenorphine, and glucuronide metabolites in umbilical cord plasma. The average accuracy (percentage error) and precision (relative standard deviation) were buprenorphine and metabolite concentrations. This method was successfully applied to the analysis of cord blood from women with known buprenorphine or methadone use during pregnancy. Copyright © 2015 John Wiley & Sons, Ltd.

  8. Synthesis of Ethyl Salicylate Using Household Chemicals

    Science.gov (United States)

    Solomon, Sally; Hur, Chinhyu; Lee, Alan; Smith, Kurt

    1996-02-01

    Ethyl salicylate is synthesized, isolated, and characterized in a three-step process using simple equipment and household chemicals. First, acetylsalicylic acid is extracted from aspirin tablets with isopropyl alcohol, then hydrolyzed to salicylic acid with muriatic acid, and finally, the salicylic acid is esterified using ethanol and a boric acid catalyst. The experiment can be directed towards high school or university level students who have sufficient background in organic chemistry to recognize the structures and reactions that are involved.

  9. Interaction between rhein acyl glucuronide and methotrexate based on human organic anion transporters.

    Science.gov (United States)

    Yuan, Yuan; Yang, Hua; Kong, Linghua; Li, Yuan; Li, Ping; Zhang, Hongjian; Ruan, Jianqing

    2017-11-01

    Rhein, a major bioactive compound of many medicinal herbs and the prodrug of diacerein, is often used with low dose of methotrexate as drug combination to treat rheumatoid arthritis. In this study, potential drug-drug interaction between methotrexate and rhein was investigated based on organic anion transporters (OAT). Our study demonstrated that rhein acyl glucuronide (RAG), the major metabolite of rhein in the human blood circulation, significantly inhibited the uptake of p-aminohippurate in hOAT1 transfected cells with IC50 value of 691 nM and estrone sulfate uptake in hOAT3 transfected cells with IC50 value of 78.5 nM. As the substrate of both hOAT1 and hOAT3, the methotrexate transport was significantly inhibited by RAG in hOAT1 transfected cells at 50 μM and hOAT3 transfected cells at 1 μM by 69% and 87%, respectively. Further in vivo study showed that after co-administrated with RAG in rats the AUC0-24 values of methotrexate increased from 3109 to 5370 ng/mL*hr and the t1/2 was prolonged by 40.5% (from 7.4 to 10.4 h), demonstrating the inhibitory effect of RAG on methotrexate excretion. In conclusion, rhein acyl glucuronide could significantly decrease the transport of methotrexate by both hOAT1 and hOAT3. The combination use of rhein, diacerein or other rhein-containing herbs with methotrexate may cause obvious drug-drug interaction and require close monitoring for potential drug interaction in clinical practice. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Protective Effect of Ethyl Acetate Fraction of Stereospermum Suaveolens Against Hepatic Oxidative Stress in STZ Diabetic Rats.

    Science.gov (United States)

    Balasubramanian, Thirumalaiswamy; Senthilkumar, G P; Karthikeyan, M; Chatterjee, Tapan Kumar

    2013-07-01

    Stereospermum suaveolens is a folk remedy for the treatment of diabetes and liver disorders in southern parts of India. In the present study, the protective effect of the ethyl acetate fraction of ethanol extract from S. suaveolens against hepatic oxidative stress was evaluated in streptozotocin (STZ)-induced diabetic rats for 14 days. The ethyl acetate fraction was administered orally to the STZ diabetic rats at the doses of 200 and 400 mg/kg. Blood glucose level was measured according to glucose oxidase method. In order to determine hepatoprotective activity, changes in the levels of serum biomarker enzymes such as aspartate transaminase (AST), alanine transaminase (ALT), and serum alkaline phosphatase (SALP) were assessed in the ethyl acetate fraction treated diabetic rats and were compared with the levels in diabetic control rats. In addition, the antioxidant activity of ethyl acetate fraction was evaluated using various hepatic parameters such as thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). It was found that administration of ethyl acetate fraction (200 and 400 mg/kg) produced a significant (P ethyl acetate fraction on the liver tissues of diabetic rats. It was concluded from this study that the ethyl acetate fraction from ethanol extract of S. suaveolens modulates the activity of enzymatic and nonenzymatic antioxidants and enhances the defense against hepatic oxidative stress in STZ-induced diabetic rats.

  11. Determination of polydimethylsiloxane–water partition coefficients for ten 1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene-related compounds and twelve polychlorinated biphenyls using gas chromatography/mass spectrometry

    Science.gov (United States)

    Eganhouse, Robert P.

    2016-01-01

    Polymer-water partition coefficients (Kpw) of ten DDT-related compounds were determined in pure water at 25 °C using commercial polydimethylsiloxane-coated optical fiber. Analyte concentrations were measured by thermal desorption-gas chromatography/full scan mass spectrometry (TD–GC/MSFS; fibers) and liquid injection-gas chromatography/selected ion monitoring mass spectrometry (LI–GC/MSSIM; water). Equilibrium was approached from two directions (fiber uptake and depletion) as a means of assessing data concordance. Measured compound-specific log Kpw values ranged from 4.8 to 6.1 with an average difference in log Kpw between the two approaches of 0.05 log units (∼12% of Kpw). Comparison of the experimentally-determined log Kpw values with previously published data confirmed the consistency of the results and the reliability of the method. A second experiment was conducted with the same ten DDT-related compounds and twelve selected PCB (polychlorinated biphenyl) congeners under conditions characteristic of a coastal marine field site (viz., seawater, 11 °C) that is currently under investigation for DDT and PCB contamination. Equilibration at lower temperature and higher ionic strength resulted in an increase in log Kpw for the DDT-related compounds of 0.28–0.49 log units (61–101% of Kpw), depending on the analyte. The increase in Kpw would have the effect of reducing by approximately half the calculated freely dissolved pore-water concentrations (Cfree). This demonstrates the importance of determining partition coefficients under conditions as they exist in the field.

  12. Determination of 1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene and related compounds in marine pore water by automated thermal desorption-gas chromatography/mass spectrometry using disposable optical fiber

    Science.gov (United States)

    Eganhouse, Robert P.; DiFilippo, Erica L

    2015-01-01

    A method is described for determination of ten DDT-related compounds in marine pore water based on equilibrium solid-phase microextraction (SPME) using commercial polydimethylsiloxane-coated optical fiber with analysis by automated thermal desorption-gas chromatography/mass spectrometry (TD-GC/MS). Thermally cleaned fiber was directly exposed to sediments and allowed to reach equilibrium under static conditions at the in situ field temperature. Following removal, fibers were rinsed, dried and cut into appropriate lengths for storage in leak-tight containers at -20°C. Analysis by TD-GC/MS under full scan (FS) and selected ion monitoring (SIM) modes was then performed. Pore-water method detection limits in FS and SIM modes were estimated at 0.05-2.4ng/L and 0.7-16pg/L, respectively. Precision of the method, including contributions from fiber handling, was less than 10%. Analysis of independently prepared solutions containing eight DDT compounds yielded concentrations that were within 6.9±5.5% and 0.1±14% of the actual concentrations in FS and SIM modes, respectively. The use of optical fiber with automated analysis allows for studies at high temporal and/or spatial resolution as well as for monitoring programs over large spatial and/or long temporal scales with adequate sample replication. This greatly enhances the flexibility of the technique and improves the ability to meet quality control objectives at significantly lower cost.

  13. An improved method of determining ethanol use in a chronic pain population.

    Science.gov (United States)

    Crews, Bridgit; West, Robert; Gutierrez, Ronita; Latyshev, Sergey; Mikel, Charles; Almazan, Perla; Pesce, Amadeo; West, Cameron; Rosenthal, Murray

    2011-01-01

    Determination of ethanol use in the pain patient population being treated with chronic opioid therapy is critically important to the treating physician. Urinary ethanol, ethyl glucuronide (EtG), and ethyl sulfate (EtS) have been used to identify alcohol use. Because urine samples are shipped to reference laboratories, the possibility of glucose fermentation during transit producing ethanol complicates interpretation. The purpose of this study was to establish whether ethanol-positive urine samples were due to ingestion or fermentation during shipping. The authors obtained 94 ethanol-positive urine samples from pain patients, which were further tested for EtG, EtS, and glucose. Only 62 of the 94 samples contained EtS or EtS. Of the 94 samples, 63 samples had glucose values above 10 mg/dL. Four of the 32 EtG-negative patients had ethanol levels that were nonphysiologic. Limitations of the study include the lack of demographic data beyond treatment with opioids for chronic pain. Roughly one-third of the time, ethanol-positive urine samples that have been shipped were positive because of fermentation and not because of patient alcohol consumption. This method is a combination of urinary ethanol measurement and liquid chromatography tandem mass spectrometry quantitation of both EtG and EtS. In the absence of these metabolites, the presence of urinary ethanol is attributed to fermentation. The improvement is a better definition of the source of the ethanol. Confirmatory testing showing the presence of the ethanol metabolites EtG and EtS is needed to validate that the ethanol is due to consumption. The presence of glucose, while common in the ethanol-positive samples, is not an absolute indicator that the ethanol was due to fermentation.

  14. Development, validation and application of a comprehensive stereoselective LC/MS–MS assay for bupropion and oxidative, reductive, and glucuronide metabolites in human urine

    Science.gov (United States)

    Teitelbaum, Aaron M.; Flaker, Alicia M.; Kharasch, Evan D.

    2016-01-01

    A stereoselective assay was developed for the quantification of bupropion and oxidative, reductive, and glucuronide metabolites (16 analytes total) in human urine. Initially, authentic glucuronide standards obtained from commercial sources were found to be incorrectly labeled with regard to stereochemistry; the correct stereochemistry was unequivocally reassigned. A trifurcated urine sample preparation and analysis procedure was employed for the stereoselective analysis of bupropion, hydroxybupropion, erythrohydrobupropion, and threohydrobupropion enantiomers, and hydroxybupropion, erythrohydrobupropion and threohydrobupropion β-d-glucuronide diastereomers in urine. Method 1 stereoselectively analyzed bupropion (R and S), and unconjugated free hydroxybupropion (R,R and S,S), erythrohydrobupropion (1R,2S and 1S,2R), and threohydrobupropion (1R,2R and 1S,2S) using chiral chromatography with an α1-acid glycoprotein column. Because no hydroxybupropion β-d-glucuronide standards were commercially available, method 2 stereoselectively analyzed total hydroxybupropion aglycones (R,R and S,S-hydroxybupropion) after urine hydrolysis by β-glucuronidase. Hydroxybupropion β-d-glucuronide (R,R and S,S) urine concentrations were calculated as the difference between total and free hydroxybupropion (R,R and S,S) concentrations. Due to incomplete μ-glucuronidase hydrolysis of erythrohydrobupropion and threohydrobupropion β-d-glucuronide diastereomers, method 3 stereoselectively analyzed intact erythrohydrobupropion and threohydrobupropion β-d-glucuronide diastereomers using C18 column chromatography. All analytes were quantified by positive ion electrospray tandem mass spectrometry. The assay was fully validated over analyte-specific concentrations. Intra- and inter assay precision were within 15% for each analyte. The limits of quantification for bupropion (R and S), hydroxybupropion (R,R and S,S), threohydrobupropion (1S,2S and 1R,2R), erythrohydrobupropion (1R,2S and 1S,2R

  15. Pallidol hexa-acetate ethyl acetate monosolvate.

    Science.gov (United States)

    Mao, Qinyong; Taylor, Dennis K; Ng, Seik Weng; Tiekink, Edward R T

    2013-01-01

    The entire mol-ecule of pallidol hexa-acetate {systematic name: (±)-(4bR,5R,9bR,10R)-5,10-bis-[4-(acet-yloxy)phen-yl]-4b,5,9b,10-tetra-hydro-indeno-[2,1-a]indene-1,3,6,8-tetrayl tetra-acetate} is completed by the application of twofold rotational symmetry in the title ethyl acetate solvate, C40H34O12·C4H8O2. The ethyl acetate mol-ecule was highly disordered and was treated with the SQUEEZE routine [Spek (2009 ▶). Acta Cryst. D65, 148-155]; the crystallographic data take into account the presence of the solvent. In pallidol hexa-acetate, the dihedral angle between the fused five-membered rings (r.m.s. deviation = 0.100 Å) is 54.73 (6)°, indicating a significant fold in the mol-ecule. Significant twists between residues are also evident as seen in the dihedral angle of 80.70 (5)° between the five-membered ring and the pendent benzene ring to which it is attached. Similarly, the acetate residues are twisted with respect to the benzene ring to which they are attached [C-O(carb-oxy)-C-C torsion angles = -70.24 (14), -114.43 (10) and -72.54 (13)°]. In the crystal, a three-dimensional architecture is sustained by C-H⋯O inter-actions which encompass channels in which the disordered ethyl acetate mol-ecules reside.

  16. in Binary Liquid Mixtures of Ethyl benzoate

    Directory of Open Access Journals (Sweden)

    Shaik Babu

    2012-01-01

    Full Text Available Ultrasonic velocity is measured at 2MHz frequency in the binary mixtures of Ethyl Benzoate with 1-Propanol, 1-Butanol, 1-Pentanol and theoretical values of ultrasonic velocity have been evaluated at 303K using Nomoto's relation, Impedance relation, Ideal mixture relation, Junjie's method and free length theory. Theoretical values are compared with the experimental values and the validity of the theories is checked by applying the chi-square test for goodness of fit and by calculating the average percentage error (APE. A good agreement has been found between experimental and Nomoto’s ultrasonic velocity.

  17. A review of morphine and morphine-6-glucuronide's pharmacokinetic-pharmacodynamic relationships in experimental and clinical pain

    DEFF Research Database (Denmark)

    Sverrisdóttir, Eva; Lund, Trine Meldgaard; Olesen, Anne Estrup

    2015-01-01

    Morphine is a widely used opioid for treatment of moderate to severe pain, but large interindividual variability in patient response and no clear guidance on how to optimise morphine dosage regimen complicates treatment strategy for clinicians. Population pharmacokinetic-pharmacodynamic models can...... a detailed overview of the published human population pharmacokinetic-pharmacodynamic studies for morphine analgesia in addition to basic drug disposition and pharmacological properties of morphine and its analgesic active metabolite, morphine-6-glucuronide, that may help identify future covariates....... Furthermore, based on simulations from key pharmacokinetic-pharmacodynamic models, the contribution of morphine-6-glucuronide to the analgesic response in patients with renal insufficiency was investigated. Simulations were also used to examine the impact of effect-site equilibration half-life on time course...

  18. Is enzymatic hydrolysis a reliable analytical strategy to quantify glucuronidated and sulfated polyphenol metabolites in human fluids?

    Science.gov (United States)

    Quifer-Rada, Paola; Martínez-Huélamo, Miriam; Lamuela-Raventos, Rosa M

    2017-07-19

    Phenolic compounds are present in human fluids (plasma and urine) mainly as glucuronidated and sulfated metabolites. Up to now, due to the unavailability of standards, enzymatic hydrolysis has been the method of choice in analytical chemistry to quantify these phase II phenolic metabolites. Enzymatic hydrolysis procedures vary in enzyme concentration, pH and temperature; however, there is a lack of knowledge about the stability of polyphenols in their free form during the process. In this study, we evaluated the stability of 7 phenolic acids, 2 flavonoids and 3 prenylflavanoids in urine during enzymatic hydrolysis to assess the suitability of this analytical procedure, using three different concentrations of β-glucuronidase/sulfatase enzymes from Helix pomatia. The results indicate that enzymatic hydrolysis negatively affected the recovery of the precursor and free-form polyphenols present in the sample. Thus, enzymatic hydrolysis does not seem an ideal analytical strategy to quantify glucuronidated and sulfated polyphenol metabolites.

  19. Evaluation Lactogenic Activity of Ethyl Acetate Fraction of Torbangun (Coleus amboinicus L.) Leaves

    Science.gov (United States)

    Damanik, R. M.; Kustiyah, L.; Hanafi, M.; Iwansyah, A. C.

    2017-12-01

    This study aimed to assess the lactogenic property of ethyl acetate fraction of torbangun (Coleus amboinicus L.) leaves and to identify the compounds that responsibility as ‘milk booster’ using LC- MS approach. Lactagogue activity was evaluated in terms of quantity of milk produced from the rats treated with commercial milk booster (AF), ethyl acetate fraction of torbangun leaves (EA), water extraction of torbangun (AQ) and kaempferol (KP). The feed was given orally every two days and starting from Day 2 after giving birth until Day 28. The performance of milk production was measured along the experimental period by weight-suckle-weight method. The level of prolactin serum was determined by ELISA methods. Histopathological analysis of mammary gland, liver, intestines and kidney tissues was carried out. Moreover, in order to profiling and identification of compounds of ethyl acetate fraction, ultra-performance liquid chromatography quadrupole time of flight to electrospray ionization mass spectrometry (UPLC-QTOF-ESI-MS) in the positive-ion mode was performed. The ethyl acetate fraction of torbangun leaves (EA) was induced milk production about 17%, and AF 22% and KP 51% compared to the control group. Meanwhile, the EA was not significantly stimulate the synthesis of serum prolactin at Day 14 and Day 28 (p>0.05). Administration of EA did not cause any signs or symptoms of toxicity. In addition, a total of ten compounds was identified by UPLC-QTOF-ESI/MS in the ethyl acetate fraction of the leaves of C. amboinicus, mostly phenolic compounds, flavonols and some of their glycoside derivatives, such as: digiprolatone, and kaempferol-3-7-O-di-rhamnopyranoside. The present study reveals the ethyl acetate fraction of torbangun leaves and its bioactive compounds has the potency as a remedy for stimulating and improving milk production.

  20. 21 CFR 172.872 - Methyl ethyl cellulose.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Methyl ethyl cellulose. 172.872 Section 172.872... CONSUMPTION Multipurpose Additives § 172.872 Methyl ethyl cellulose. The food additive methyl ethyl cellulose... a cellulose ether having the general formula [C6H(10 -x-y)O5(CH3)x(C2H5)y]n, where x is the number...

  1. Structure determination of two structural analogs, named 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-fluorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C23H16F2N4S) and 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-chlorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C23H16ClFN4S) by synchrotron X-ray powder diffraction

    Energy Technology Data Exchange (ETDEWEB)

    Gündoğdu, Gülsüm; Aytaç, Sevim Peri; Müller, Melanie; Tozkoparan, Birsen; Kaynak, Filiz Betül

    2017-12-01

    Two novel compounds, 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-fluorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C23H16F2N4S) (1) and 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-chlorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C23H16ClFN4S) (2), have been designed and synthesized as cytotoxic agents. The compounds were characterized by infrared, proton nuclear magnetic resonance, mass spectral data, elemental analysis and X-ray powder diffraction. The present study comprises spectral data and crystal structures of these novel compounds determined from synchrotron X-ray powder diffraction data. The structure solutions were obtained by simulated annealing. The final structures were achieved by Rietveld refinement using soft restraints for all bond lengths, bond angles, and planar groups. Both compounds crystallize in space group$P\\bar 1$,Z= 2, with the unit-cell parametersa= 6.37433(9),b= 11.3641(2),c= 14.09115(19) Å,α= 80.1740(8)°,β= 85.1164(8)°,γ= 80.9831(10)°,V= 991.55(3) Å3of compound (1) anda= 6.53736(6),b= 11.55725(15),c= 14.01373(13) Å,α= 80.3323(7)°,β= 84.8939(6)°,γ= 79.3954(8)°,V= 1024.08(2) Å3of compound (2). Structural analyses reveal that the title compounds are isostructural.

  2. Neonatal Maturation of Paracetamol (Acetaminophen) Glucuronidation, Sulfation, and Oxidation Based on a Parent-Metabolite Population Pharmacokinetic Model.

    Science.gov (United States)

    Cook, Sarah F; Stockmann, Chris; Samiee-Zafarghandy, Samira; King, Amber D; Deutsch, Nina; Williams, Elaine F; Wilkins, Diana G; Sherwin, Catherine M T; van den Anker, John N

    2016-11-01

    This study aimed to model the population pharmacokinetics of intravenous paracetamol and its major metabolites in neonates and to identify influential patient characteristics, especially those affecting the formation clearance (CL formation ) of oxidative pathway metabolites. Neonates with a clinical indication for intravenous analgesia received five 15-mg/kg doses of paracetamol at 12-h intervals (paracetamol, paracetamol-glucuronide, paracetamol-sulfate, and the combined oxidative pathway metabolites (paracetamol-cysteine and paracetamol-N-acetylcysteine) were simultaneously modeled in NONMEM 7.2. The model incorporated 259 plasma and 350 urine samples from 35 neonates with a mean gestational age of 33.6 weeks (standard deviation 6.6). CL formation for all metabolites increased with weight; CL formation for glucuronidation and oxidation also increased with postnatal age. At the mean weight (2.3 kg) and postnatal age (7.5 days), CL formation estimates (bootstrap 95% confidence interval; between-subject variability) were 0.049 L/h (0.038-0.062; 62 %) for glucuronidation, 0.21 L/h (0.17-0.24; 33 %) for sulfation, and 0.058 L/h (0.044-0.078; 72 %) for oxidation. Expression of individual oxidation CL formation as a fraction of total individual paracetamol clearance showed that, on average, fractional oxidation CL formation increased paracetamol and its metabolites in neonates. Maturational changes in the fraction of paracetamol undergoing oxidation were small relative to between-subject variability.

  3. Interaction of Ethyl Alcohol Vapor with Sulfuric Acid Solutions

    Science.gov (United States)

    Leu, Ming-Taun

    2006-01-01

    We investigated the uptake of ethyl alcohol (ethanol) vapor by sulfuric acid solutions over the range approx.40 to approx.80 wt % H2SO4 and temperatures of 193-273 K. Laboratory studies used a fast flow-tube reactor coupled to an electron-impact ionization mass spectrometer for detection of ethanol and reaction products. The uptake coefficients ((gamma)) were measured and found to vary from 0.019 to 0.072, depending upon the acid composition and temperature. At concentrations greater than approx.70 wt % and in dilute solutions colder than 220 K, the values approached approx.0.07. We also determined the effective solubility constant of ethanol in approx.40 wt % H2SO4 in the temperature range 203-223 K. The potential implications to the budget of ethanol in the global troposphere are briefly discussed.

  4. Quercetin-3-O-glucuronide induces ABCA1 expression by LXRα activation in murine macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Ohara, Kazuaki, E-mail: Kazuaki_Ohara@kirin.co.jp [Research Laboratories for Health Science and Food Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan); Wakabayashi, Hideyuki [Laboratory for New Product Development, Kirin Beverage Company Limited, 1-17-1 Namamugi, Tsurumi-ku, Yokohama 230-8628 (Japan); Taniguchi, Yoshimasa [Research Laboratories for Health Science and Food Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan); Shindo, Kazutoshi [Department of Food and Nutrition, Japan Women’s University, 2-8-1 Mejirodai, Bunkyo-ku, Tokyo 112-8681 (Japan); Yajima, Hiroaki [Research Laboratories for Health Science and Food Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan); Yoshida, Aruto [Central Laboratories for Key Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan)

    2013-11-29

    Highlights: •The major circulating quercetin metabolite (Q3GA) activated LXRα. •Q3GA induced ABCA1 via LXRα activation in macrophages. •Nelumbo nucifera leaf extracts contained quercetin glycosides. •N. nucifera leaf extract feeding elevated HDLC in mice. -- Abstract: Reverse cholesterol transport (RCT) removes excess cholesterol from macrophages to prevent atherosclerosis. ATP-binding cassette, subfamily A, member 1 (ABCA1) is a crucial cholesterol transporter involved in RCT to produce high density lipoprotein-cholesterol (HDLC), and is transcriptionally regulated by liver X receptor alpha (LXRα), a nuclear receptor. Quercetin is a widely distributed flavonoid in edible plants which prevented atherosclerosis in an animal model. We found that quercetin-3-O-glucuronide (Q3GA), a major quercetin metabolite after absorption from the digestive tract, enhanced ABCA1 expression, in vitro, via LXRα in macrophages. In addition, leaf extracts of a traditional Asian edible plant, Nelumbo nucifera (NNE), which contained abundant amounts of quercetin glycosides, significantly elevated plasma HDLC in mice. We are the first to present experimental evidence that Q3GA induced ABCA1 in macrophages, and to provide an alternative explanation to previous studies on arteriosclerosis prevention by quercetin.

  5. Development of an on-line solid phase extraction ultra-high-performance liquid chromatography technique coupled to tandem mass spectrometry for quantification of bisphenol S and bisphenol S glucuronide: Applicability to toxicokinetic investigations.

    Science.gov (United States)

    Grandin, Flore; Picard-Hagen, Nicole; Gayrard, Véronique; Puel, Sylvie; Viguié, Catherine; Toutain, Pierre-Louis; Debrauwer, Laurent; Lacroix, Marlène Z

    2017-12-01

    Regulatory measures and public concerns regarding bisphenol A (BPA) have led to its replacement by structural analogues, such as Bisphenol S (BPS), in consumer products. At present, no toxicokinetic investigations have been conducted to assess the factors determining human internal exposure to BPS for subsequent risk assessment. Toxicokinetic studies require reliable analytical methods to measure the plasma concentrations of BPS and its main conjugated metabolite, BPS-glucuronide (BPS-G). An efficient on-line SPE-UPLC-MS/MS method for the simultaneous quantification of BPS and BPS-G in ovine plasma was therefore developed and validated in accordance with the European Medicines Agency guidelines for bioanalytical method validation. This method has a limit of quantification of 3ngmL-1 for BPS and 10ngmL-1 for BPS-G, an analytical capacity of 200 samples per day, and is particularly well suited to toxicokinetic studies. Use of this method in toxicokinetic studies in sheep showed that BPS, like BPA, is efficiently metabolized into its glucuronide form. However, the clearances and distributions of BPS and BPS-G were lower than those of the corresponding unconjugated and glucuroconjugated forms of BPA. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Chiral quizalofop-ethyl and its metabolite quizalofop-acid in soils: Enantioselective degradation, enzymes interaction and toxicity to Eisenia foetida.

    Science.gov (United States)

    Ma, Lin; Liu, Hui; Qu, Han; Xu, Yangguang; Wang, Peng; Sun, Mingjing; Zhou, Zhiqiang; Liu, Donghui

    2016-06-01

    An enantioselective chromatographic method to analyze enantiomers of quizalofop-ethyl and its metabolite quizalofop-acid was established using a high-performance liquid chromatography (HPLC) on (R, R) Whelk-O 1 column. The enantioselective degradation kinetics of quizalofop-ethyl and quizalofop-acid in three soils were investigated. Moreover, the interaction with urease and catalase in the soils and the acute toxicity to Eisenia foetida of quizalofop-ethyl were also determined in order to assess their metabolism mechanism and environmental risk. From the results, quizalofop-ethyl was configurationally stable and was hydrolyzed rapidly to quizalofop-acid, which also degraded enantioselectively but slowly, and the inversion of the S-(-)-quizalofop-acid into the R-(+)-quizalofop-acid was observed in Xinxiang soil. In addition, quizalofop-ethyl and quizalofop-acid enantioselectively affected urease activity but not catalase. The acute toxicity assays to earthworm indicated that the racemic quizalofop-ethyl and quizalofop-acid were more toxic than quizalofop-p-ethyl and quizalofop-p-acid respectively, dramatically, the toxicity of the metabolite was much higher than the parent compound. These results revealed the enantioselective degradation of quizalofop-ethyl and quizalofop-acid, and the differences of toxicity among the enantiomers of the parent compound and the metabolite, which should be considered in future environmental risk evaluation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Phytochemical screening and antioxidant activity of ethanolic extract and ethyl acetate fraction from basil leaf (Ocimum basilicum L.) by DPPH radical scavenging method

    Science.gov (United States)

    Warsi; Sholichah, A. R.

    2017-11-01

    Basil leaf (Ocimum basilicum L.) contains various compounds such as flavonoid, alkaloid, phenol and essential oil, so it needs to be fractionated to find out the flavonoid compound with the greatest potential as an antioxidant. This research was aimed to know the chemical compound, antioxidant potential of ethanolic extract and ethyl acetate fraction from basil leaf. The basil leaf was extracted by maceration using ethanol 70 %. The crude extract was fractionated with ethyl acetate. The ethanolic extract and ethyl acetate fraction were screened of phytochemical content including identification of flavonoids, alkaloids and polyphenolics. The antioxidant activity of the ethanolic extract and ethyl acetate fraction were tested qualitatively with 2,2-diphenyl-1-picrylhydrazyl (DPPH) and phosphomolybdate. Its antioxidant activity was determined quantitatively using DPPH radical scavenging method. Phytochemical screening test showed that ethanolic extract and ethyl acetate fraction from basil leaf contain flavonoids, polyphenolics, and alkaloids. The qualitative analysis of antioxidant activity of ethanolic extract and ethyl acetate fraction from basil leaf showed an antioxidant activity. The IC50 value of ethanolic extract, ethyl acetate fraction and quercetin were 1,374.00±6.20 389.00±1.00 2.10±0.01μg/mL, respectively. The research showed that antioxidant activity of the ethyl acetate fraction more potential than the ethanol extract of the basil leaf, but less than quercetin.

  8. Cyclohexenones Through Addition of Ethyl Acetoacetate to 3-Aryl-1 ...

    African Journals Online (AJOL)

    Chalcone derivatives 3a–i containing a thiophene ring were prepared by the condensation of 1-(thiophen-3-yl)ethanone with aromatic aldehydes in excellent yields. The Michael addition of ethyl acetoacetate 4 to chalcone derivatives 3a–i resulted in the formation of nine novel ethyl 6-aryl ...

  9. 2,6-Bis(9-ethyl-9H-carbazolylmethylenecyclohexanone

    Directory of Open Access Journals (Sweden)

    Abdullah M. Asiri

    2009-10-01

    Full Text Available The title compound, 2,6-bis(ethyl-9-ethyl-9H-carbazolylmethylenecyclohexanone has been synthesized by condensation of 9-ethylcarbazole-3-aldehyde and cyclohexanone in ethanol in the presence of pyridine. The structure of this new compound was confirmed by elemental analysis, IR, 1H NMR, 13C NMR and EI-MS spectral analysis.

  10. Graft Copolymerization of Acrylonitrile and Ethyl Methacrylate on ...

    African Journals Online (AJOL)

    Graft copolymers of Acrylonitrile and ethyl methcrylate on dextrin were prepared by the use of ceric ion initiator in aqueous medium at 290C. The molecular weight of grafted poly(ethyl methacrylate) chains were higher than for polyacrylonitrile grafts; but the latter were more frequently grafted on the backbone polymer.

  11. Ethyl acetate production by the elusive alcohol acetyltransferase from yeast

    NARCIS (Netherlands)

    Kruis, Alex; Levisson, Mark; Mars, Astrid E.; Ploeg, van der Max; Garcés Daza, Fernando; Ellena, Valeria; Kengen, Servé W.M.; Oost, van der John; Weusthuis, Ruud A.

    2017-01-01

    Ethyl acetate is an industrially relevant ester that is currently produced exclusively through unsustainable processes. Many yeasts are able to produce ethyl acetate, but the main responsible enzyme has remained elusive, hampering the engineering of novel production strains. Here we describe the

  12. Antibacterial activity of various fractions of ethyl acetate extract from ...

    African Journals Online (AJOL)

    The antibacterial activity of various fractions of ethyl acetate extract isolated from edible fungi, Tirmania pinoyi (Maire) Malençon, growing in Algeria, was investigated. Extraction was done by the Soxhlet and the fractions obtained were purified with silica-gel column. Two fractions of ethyl acetate extract were tested against ...

  13. Antidiarrheal Activity of the Ethyl Acetate Extract of Morinda ...

    African Journals Online (AJOL)

    Purpose: The objective of the study was to investigate the ethyl acetate extract of Morinda morindoides (Baker) Milne-Redh (Rubiaceae) (MM-EA) properties against experimental diarrheoa induced by castor oil in albino Wistar rats. Methods: The ethyl acetate extract of Morinda morindoides (250, 500, and 1000 mg/kg body ...

  14. short communication chemical constituents of the ethyl acetate ...

    African Journals Online (AJOL)

    a

    ABSTRACT. The antibacterial activities of ethyl acetate, methanol and aqueous extracts of the stem bark of Dichrostachys cinerea and the roots of Parkia bicolor have been evaluated. Ethyl acetate extracts have been investigated, studies that led to a series of known compounds, amongst which many are reported here for ...

  15. Tuning the Molar Composition of "Charge-Shifting" Cationic Copolymers Based on 2-(N,N-Dimethylamino)Ethyl Acrylate and 2-(tert-Boc-Amino)Ethyl Acrylate.

    Science.gov (United States)

    Ho, Hien The; Bohec, Maël Le; Frémaux, Julien; Piogé, Sandie; Casse, Nathalie; Fontaine, Laurent; Pascual, Sagrario

    2017-03-01

    Copolymers of 2-(N,N-dimethylamino)ethyl acrylate (DMAEA) and 2-(tert-Boc-amino)ethyl acrylate (tBocAEA) are synthesized by reversible addition-fragmentation chain transfer polymerization in a controlled manner with defined molar masses and narrow molar masses distributions (Ð ≤ 1.17). Molar compositions of the P(DMAEA-co-tBocAEA) copolymers are assessed by means of (1) H NMR. A complete screening in molar composition is studied from 0% of DMAEA to 100% of DMAEA. Reactivity ratios of both comonomers are determined by the extended Kelen-Tüdos method (r DMAEA = 0.81 and rtBocAEA = 0.99). © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Reaction rate coefficients of OH radicals and Cl atoms with ethyl propanoate, n-propyl propanoate, methyl 2-methylpropanoate, and ethyl n-butanoate.

    Science.gov (United States)

    Cometto, Pablo M; Daële, Véronique; Idir, Mahmoud; Lane, Silvia I; Mellouki, Abdelwahid

    2009-10-08

    Kinetics of the reactions of OH radicals and Cl atoms with four saturated esters have been investigated. Rate coefficients for the gas-phase reactions of OH radicals with ethyl propanoate (k(1)), n-propyl propanoate (k(2)), methyl 2-methylpropanoate (k(3)), and ethyl n-butanoate (k(4)) were measured using a conventional relative rate method and the pulsed laser photolysis-laser induced fluorescence technique. At (296 +/- 2) K, the rate coefficients obtained by the two methods were in good agreement. Significant curvatures in the Arrhenius plots have been observed in the temperature range 243-372 K for k(1), k(3), and k(4). The rate coefficients for the reactions of the four esters with Cl atoms were determined using the relative rate method at (296 +/- 2) K and atmospheric pressure. The values obtained are presented, compared with the literature values when they exist, and discussed. Reactivity trends and atmospheric implications for these esters are also presented.

  17. The sensitivity of soil enzymes, microorganisms and spring wheat to soil contamination with carfentrazone-ethyl.

    Science.gov (United States)

    Tomkiel, Monika; Baćmaga, Małgorzata; Borowik, Agata; Wyszkowska, Jadwiga; Kucharski, Jan

    2017-11-27

    Herbicides pose a significant threat to the natural environment, in particular in soils that are most exposed to plant protection agents. Prolonged herbicide use leads to changes in soil metabolism and decreases soil productive potential. In this study, the influence of carfentrazone-ethyl (CE) on the microbiological and biochemical properties of soil and the yield of Triticum aestivum L. was evaluated. Carfentrazone-ethyl was applied to sandy loam (pHKCl - 7.0) in doses of 0.000, 0.264, 5.280, 10.56, 21.18, 42.24, 84.48 and 168.96 µg kg-1 DM soil. Soil samples were subjected to microbiological and biochemical analyses on experimental days 30 and 60. Carfentrazone-ethyl disrupted the biological equilibrium in soil by decreasing the abundance and biodiversity of soil-dwelling microorganisms, the activity of soil enzymes, the values of the biochemical activity indicator and spring wheat yields. Carfentrazone-ethyl had the most adverse effects when applied in doses many fold higher than those recommended by the manufacturer. The toxic effects of CE were also determined by its soil retention time. Soil treated with CE was characterized by higher counts of oligotrophic bacteria, organotrophic bacteria, bacteria of the genus Azotobacter, actinomycetes and fungi on day 60, and spore-forming oligotrophic bacteria on day 30. The activity of dehydrogenases, urease, alkaline phosphatase and β-glucosidase was higher on day 30 than on day 60.

  18. Ethyl vinyl chloride vapocoolant spray fails to decrease pain associated with intravenous cannulation in children.

    Science.gov (United States)

    Costello, Mary; Ramundo, Maria; Christopher, Norman C; Powell, Keith R

    2006-09-01

    The purpose of the study was to determine the effect of ethyl vinyl chloride vapocoolant spray on pain reported by children undergoing intravenous cannulation. A randomized, double-blinded, placebo-controlled trial was conducted on eligible children between the ages of 9 and 18 years seen in a pediatric emergency department and requiring intravenous cannulation. Informed consent was obtained, and children were randomized to receive ethyl vinyl chloride spray, isopropyl alcohol spray, or no spray (control group). Patient demographics and information pertaining to each intravenous cannulation were recorded. Children indicated the degree of pain associated with intravenous cannulation on a 100-mm visual analog scale (VAS) compared to a baseline pain score of "zero." Statistical analysis was performed by using Stata version 7. One hundred twenty-seven subjects were enrolled: 37 received ethyl vinyl chloride vapocoolant spray, 48 received isopropyl alcohol spray (placebo), and 42 received no pretreatment. Mean VAS scores for pain experienced during cannulation were 34, 33, and 31 mL for each group, respectively. Ethyl vinyl chloride vapocoolant spray failed to measurably reduce pain associated with intravenous cannulation when compared to those pretreated with isopropyl alcohol spray or receiving no intervention.

  19. Liver damage caused by hepatitis C viral infection and ethyl alcohol consumption

    Directory of Open Access Journals (Sweden)

    Kostić Velimir

    2006-01-01

    Full Text Available Background/Aim. Hepatitis C virus infection (HCV is a complex disease, most commonly chronicle (80-85%. The aim of this research was to determinate the level of the liver damage in the patients cansed by HCV in conjunction with consuming ethyl alcohol. Methods. The research included 15 patients with chronic HCV infection supported by the misuse of ethyl alcohol, as well. The diagnosis of C infection hepatitis was proved using the ELISA test and PCR method. Results. The results of the study showed the liver damage by both HCV infection and ethyl alcohol, which was verified by the presence of biochemical changes and patohystological processing of the patients (liver biopsy and prosection. Patohystological changes were at the level of liver cirrhosis and carcinoma (2 patients. There was a signficant difference between the two subgroups (p < 0.001 regarding the examined values γ-GT, PLT and PTV. The basic therapeutic procedure was to introduce this category of patients into alcohol abstinence, and, in a few patients, to apply the antivirus therapy, as well. Conclusion. Based on the number of the examined patients (n = 15, we could conclude that a prolonged ethyl alcohol misuse with the presence of HCV infection was in a correlation with the liver disease progression.

  20. Certification for copper concentration in reference material for fuel anhydro ethylic alcohol; Certificacao da concentracao de cobre em material de referencia para alcool etilico anidro combustivel (AEC)

    Energy Technology Data Exchange (ETDEWEB)

    Reis, Lindomar Augusto dos; Rocha, Marcia Silva da; Mesko, Marcia Foster; Silva, Fagner Francisco da; Quaresma, Maria Cristina Baptista; Araujo, Thiago Oliveira [Instituto Nacional de Metrologia, Normalizacao e Qualidade Industrial (DIMCI/INMETRO), Duque de Caxias, RJ (Brazil). Diretoria de Metrologia Cientifica e Industrial], E-mail: lareis@inmetro.gov.br

    2009-07-01

    This work aiming to obtain the first certified reference material for fuel anhydro ethylic alcohol relative to the copper concentration, which has his maximum limit determined by the in force legislation providing traceability and reliability for the measurement results.

  1. Kinetics and Mechanism of Pyridinolyses of Ethyl Methyl and Ethyl Propyl Chlorothiophosphates in Acetonitrile

    Energy Technology Data Exchange (ETDEWEB)

    Barai, Hasi Rani; Lee, Hai Whang [Inha Univ., Incheon (Korea, Republic of)

    2013-11-15

    The kinetic studies on the reactions of ethyl methyl (2) and ethyl propyl (4) chlorothiophosphates with X-pyridines have been carried out in acetonitrile at 35.0 .deg. C. The free energy correlations with X show biphasic concave upwards with a break point at X = H (2) and 3-Ph (4), respectively. A stepwise mechanism with a rate-limiting leaving group expulsion from the intermediate is proposed based on the magnitudes of selectivity parameters for both substrates. The considerably large values of β{sub X} = 1.50(2) and 1.44(4) with strongly basic pyridines and relatively small values of β{sub X} = 0.43(2) and 0.36(4) with weakly basic pyridines are interpreted as a change of the attacking direction of the X-pyridines from a frontside to a backside attack toward the chloride leaving group.

  2. High yielding synthesis of N-ethyl dehydroamino acids.

    Science.gov (United States)

    Monteiro, Luís S; Suárez, Ana S

    2012-10-01

    Recently we reported the use of a sequence of alkylation and dehydration methodologies to obtain N-ethyl-α, β-dehydroamino acid derivatives. The application of this N-alkylation procedure to several methyl esters of β,β-dibromo and β-bromo, β-substituted dehydroamino acids protected with standard amine protecting groups was subsequently reported. The corresponding N-ethyl, β-bromo dehydroamino acid derivatives were obtained in fair to high yields and some were used as substrates in Suzuki cross-coupling reactions to give N-ethyl, β,β-disubstituted dehydroalanine derivatives. Herein, we further explore N-ethylation of β-halo dehydroamino acid derivatives using triethyloxonium tetrafluoroborate as alkylating agent, but substituting N,N-diisopropylethylamine for potassium tert-butoxide as auxiliary base. In these conditions, for all β-halo dehydroamino acid derivatives, reactions were complete and the N-ethylated derivative could be isolated in high yield. This method was also applied for N-ethylation of non-halogenated dehydroamino acids. Again, with all compounds the reactions were complete and the N-ethyl dehydroamino acid derivatives could be isolated in high yields. Some of these N-ethyl dehydroamino acid methyl ester derivatives were converted in high yields to their corresponding acids and coupled to an amino acid methyl ester to give N-ethyl dehydrodipeptide derivatives in good yields. Thus, this method constitutes a general procedure for high yielding synthesis of N-ethylated dehydroamino acids, which can be further applied in peptide synthesis.

  3. Parameters affecting ethyl ester production by Saccharomyces cerevisiae during fermentation.

    Science.gov (United States)

    Saerens, S M G; Delvaux, F; Verstrepen, K J; Van Dijck, P; Thevelein, J M; Delvaux, F R

    2008-01-01

    Volatile esters are responsible for the fruity character of fermented beverages and thus constitute a vital group of aromatic compounds in beer and wine. Many fermentation parameters are known to affect volatile ester production. In order to obtain insight into the production of ethyl esters during fermentation, we investigated the influence of several fermentation variables. A higher level of unsaturated fatty acids in the fermentation medium resulted in a general decrease in ethyl ester production. On the other hand, a higher fermentation temperature resulted in greater ethyl octanoate and decanoate production, while a higher carbon or nitrogen content of the fermentation medium resulted in only moderate changes in ethyl ester production. Analysis of the expression of the ethyl ester biosynthesis genes EEB1 and EHT1 after addition of medium-chain fatty acid precursors suggested that the expression level is not the limiting factor for ethyl ester production, as opposed to acetate ester production. Together with the previous demonstration that provision of medium-chain fatty acids, which are the substrates for ethyl ester formation, to the fermentation medium causes a strong increase in the formation of the corresponding ethyl esters, this result further supports the hypothesis that precursor availability has an important role in ethyl ester production. We concluded that, at least in our fermentation conditions and with our yeast strain, the fatty acid precursor level rather than the activity of the biosynthetic enzymes is the major limiting factor for ethyl ester production. The expression level and activity of the fatty acid biosynthetic enzymes therefore appear to be prime targets for flavor modification by alteration of process parameters or through strain selection.

  4. Prediction of Clearance in Neonates and Infants (≤ 3 Months of Age) for Drugs That Are Glucuronidated: A Comparative Study Between Allometric Scaling and Physiologically Based Pharmacokinetic Modeling.

    Science.gov (United States)

    Mahmood, Iftekhar; Ahmad, Tasneem; Mansoor, Najia; Sharib, S M

    2017-04-01

    The objective of this study was to evaluate the predictive performances of allometric models and a physiologically based pharmacokinetic model (PBPK) to predict clearance of glucuronidated drugs in neonates (≤ 3 months of age). From the literature, clearance values for 9 drugs (glucuronidated) for neonates and adults were obtained. Three allometric models were used to predict clearances of these glucuronidated drugs. A PBPK model was developed using the physicochemical, biopharmaceutical, and metabolic properties together with known pediatric physiology and enzymatic ontogeny. The model was first developed for adult subjects and then verified using external data and then applied to simulations in neonates. The predictive performances of allometric and PBPK models were evaluated by comparing the predicted values of clearance with the observed clearance values in the neonates. For 9 drugs, there were 13 age groups (preterm and term neonates) for which prediction error in mean clearance values within 0.5- to 1.5-fold was observed in 10 and 11 age groups by 2 allometric models and a PBPK model, respectively. The proposed allometric methods can predict mean clearances of glucuronidated drugs in preterm and term neonates (≤ 3 months of age) with reasonable accuracy (within 0.5- to 1.5-fold or 50% error) and are of practical value during neonatal drug development. The predicted mean clearance values of glucuronidated drugs in neonates ≤ 3 months of age by 2 allometric methods were comparable with the PBPK model. © 2016, The American College of Clinical Pharmacology.

  5. Raloxifene glucuronidation in liver and intestinal microsomes of humans and monkeys: contribution of UGT1A1, UGT1A8 and UGT1A9.

    Science.gov (United States)

    Kishi, Naoki; Takasuka, Akane; Kokawa, Yuki; Isobe, Takashi; Taguchi, Maho; Shigeyama, Masato; Murata, Mikio; Suno, Manabu; Hanioka, Nobumitsu

    2016-01-01

    1. Raloxifene is an antiestrogen that has been marketed for the treatment of osteoporosis, and is metabolized into 6- and 4'-glucuronides by UDP-glucuronosyltransferase (UGT) enzymes. In this study, the in vitro glucuronidation of raloxifene in humans and monkeys was examined using liver and intestinal microsomes and recombinant UGT enzymes (UGT1A1, UGT1A8 and UGT1A9). 2. Although the K(m) and CL(int) values for the 6-glucuronidation of liver and intestinal microsomes were similar between humans and monkeys, and species differences in Vmax values (liver microsomes, humans > monkeys; intestinal microsomes, humans  UGT1A8 >UGT1A9 for humans, and UGT1A8 > UGT1A1 > UGT1A9 for monkeys. The activities of 4'-glucuronidation were UGT1A8 > UGT1A1 > UGT1A9 in humans and monkeys. 4. These results demonstrated that the profiles for the hepatic and intestinal glucuronidation of raloxifene by microsomes were moderately different between humans and monkeys.

  6. False-negative beta-D-glucuronidase reactions in membrane lactose glucuronide agar medium used for the simultaneous detection of coliforms and Escherichia coli from water.

    Science.gov (United States)

    Fricker, C R; DeSarno, M; Warden, P S; Eldred, B J

    2008-12-01

    Testing for beta-D-glucuronidase activity has become the basis of many methods for the detection of Escherichia coli in both food and water. Used in combination with tests for the presence of beta-D-glucuronidase, these tests offer a simple method for simultaneously detecting coliforms and E. coli. The purpose of this study was to determine the effectiveness of several different procedures in detecting beta-D-glucuronidase activity and hence in detecting E. coli. The ability of membrane lactose glucuronide agar (MLGA), Colilert-18, MI agar, Colitag and Chromocult agar to detect beta-D-glucuronidase activity was tested with over 1000 isolates of E. coli recovered from naturally contaminated water samples. Four of the media gave very similar results but MLGA failed to detect glucuronidase activity in 15.6% of the cultures tested. MLGA had very poor sensitivity for the detection of beta-D-glucuronidase activity in strains of E. coli isolated from naturally contaminated water. This is probably because of the fact that beta-D-glucuronidase activity is pH-sensitive and that acid is formed by E. coli during fermentation of lactose in MLGA. The detection of E. coli in drinking water is the primary test used to establish faecal contamination. The poor sensitivity of MLGA in detecting beta-D-glucuronidase activity suggests that this medium and others containing high concentrations of fermentable carbohydrate should not be used for the detection of E. coli.

  7. Analysis of 11-nor-Δ9 -tetrahydrocannabinol-9-carboxylic acid and its glucuronide in urine by capillary electrophoresis/mass spectrometry.

    Science.gov (United States)

    Iwamuro, Yoshiaki; Iio-Ishimaru, Reiko; Chinaka, Satoshi; Takayama, Nariaki; Hayakawa, Kazuichi

    2012-11-01

    Δ(9) -Tetrahydrocannabinol is the primary psychoactive component in cannabis, one of the most commonly used illicit drugs in the world. This paper describes a simple and rapid method for direct analysis of major metabolites of Δ(9) -tetrahydrocannabinol; 11-nor-Δ(9) -tetrahydrocannabinol-9-carboxylic acid and its glucuronide in urine by capillary electrophoresis/mass spectrometry. The only pretreatment needed for a urine sample was dilution with methanol containing an internal standard and centrifugation. Electrophoresis was carried out in an untreated fused-silica capillary (50 µm i.d. × 85 cm) filled with 40 m m ammonium formate (pH 6.4). An analysis could be completed within 10 min. For both compounds, the assay was linear over the range 0.1-10 µg/mL in urine with correlation coefficients (r(2) ) >0.99 and the limit of detection was 0.5 pg (10 nL injection). The detection yields and reproducibilities were determined at three different concentrations (0.1, 0.5 and 2 µg/mL in urine). The mean detection yields were 60-99%. The intra- and inter-day relative standard deviations of migration times were 0.063-0.19 and 0.18-0.36%, and those of peak areas were 4.2-18 and 5.9-25%, respectively. The proposed method successfully analyzed the urine samples of cannabis users. Copyright © 2012 John Wiley & Sons, Ltd.

  8. Perspectives for the biotechnological production of ethyl acetate by yeasts.

    Science.gov (United States)

    Löser, Christian; Urit, Thanet; Bley, Thomas

    2014-06-01

    Ethyl acetate is an environmentally friendly solvent with many industrial applications. The production of ethyl acetate currently proceeds by energy-intensive petrochemical processes which are based on natural gas and crude oil without exception. Microbial synthesis of ethyl acetate could become an interesting alternative. The formation of esters as aroma compounds in food has been repeatedly reviewed, but a survey which deals with microbial synthesis of ethyl acetate as a bulk product is missing. The ability of yeasts for producing larger amounts of this ester is known for a long time. In the past, this potential was mainly of scientific interest, but in the future, it could be applied to large-scale ester production from renewable raw materials. Pichia anomala, Candida utilis, and Kluyveromyces marxianus are yeasts which convert sugar into ethyl acetate with a high yield where the latter is the most promising one. Special attention was paid to the mechanism of ester synthesis including regulatory aspects and to the maximum and expectable yield. Synthesis of much ethyl acetate requires oxygen which is usually supplied by aeration. Ethyl acetate is highly volatile so that aeration results in its phase transfer and stripping. This stripping process cannot be avoided but requires adequate handling during experimentation and offers a chance for a cost-efficient process-integrated recovery of the synthesized ester.

  9. In vivo biological evaluation of {sup 131}I radiolabeled-paclitaxel glucuronide ({sup 131}I-PAC-G)

    Energy Technology Data Exchange (ETDEWEB)

    Aslan, O.; Biber Muftuler, F.Z.; Yurt Kilcar, A.; Ichedef, C.; Unak, P. [Ege Univ., Izmir (Turkey). Dept. of Nuclear Applications

    2012-07-01

    Paclitaxel (PAC) is a natural occurring diterpene alkoloid originally isolated from the bark of Taxus Brevifolia. It is one of the most important antitumor agents for clinical treatment of ovarian, breast non-small cell lung and prostate cancers. It is known that these types of cancer cells have high {beta}-glucuronidase enzyme which can catalyze the hydrolysis of glucuronides. This is why the synthesis compounds which undergo glucuronidation come into question in the imaging and therapy of these cancer cells. The aim of current study is conjugation of glucuronic acid (G) to the starting substance PAC, labeling with {sup 131}I and to perform its in vivo biological evaluation. Glucuronic acid derived paclitaxel compound [paclitaxel-glucuronide (PAC-G)] was labeled with {sup 131}I using iodogen method. According to thin layer radio chromatography (TLRC) method, the radiochemical yield of {sup 131}I-PAC-G was 84.30 {+-} 7.40% (n=10). The biodistribution of {sup 131}I-PAC-G in healthy female and male Wistar Albino rats has been investigated. Imaging studies on male Balb-C mice were performed by using the Kodak FX PRO in vivo Imaging System. The range of the breast/blood, breast/muscle; ovary/blood, ovary/muscle ratios is approximately between 1.29 and 11.34 in 240 min, and between 0.71 and 8.24 in 240 min for female rats. The prostate/blood and prostate/muscle ratio is between 1.94 and 6.95 in 30 min for male rats. All these experimental studies indicate that {sup 131}I-PAC-G may potentially be used in breast, ovary and prostate tissues as an imaging agent. Also it is thought that {sup 131}I-PAC-G bears a therapy potential because of the {sup 131}I radionuclide and can be improved with further investigations. (orig.)

  10. Use and Effectiveness of Ethyl Chloride for Hand Injections.

    Science.gov (United States)

    Franko, Orrin I; Stern, Peter J

    2017-03-01

    Limited literature supports using ethyl chloride topical spray as an anesthetic for hand injections whereas documented risks include frostbite, skin irritation, and inhalation toxicity. We hypothesize that ethyl chloride spray imparts no benefit to patients' perception of pain or anxiety for routine hand injections. We first surveyed all members of the American Society for Surgery of the Hand to discern the prevalence of ethyl chloride use during routine injections. We then performed a prospective, randomized, study at 2 institutions evaluating the efficacy of ethyl chloride spray compared with "routine injection" (no topical spray) in patients indicated for a hand injection. All patients completed a pre- and postinjection 11-point questionnaire that inquired about various components of pain and anxiety. A total of 2,083 (73% response rate) American Society for Surgery of the Hand members responded to the survey and revealed that 59% of hand surgeons always or often use ethyl chloride, and 24% never use it. There were no differences for region or practice setting, but experienced surgeons were less likely to routinely use ethyl chloride (35%) compared with younger surgeons (66%). Among 151 patients participating in the clinical study (75 with ethyl chloride), there were no differences for any outcome measure assessed. Injection pain in the spray and no-spray groups, pain after 1 minute, and overall anxiety were equivalent. Subgroup analysis demonstrated no effect of sex, anticipated anxiety, or pain threshold. Ethyl chloride is widely used among hand surgeons but imparts no benefit for routine hand injections in the clinical setting. The potential risks and costs of ethyl chloride use may outweigh its benefits. Therapeutic II. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  11. Self-assembled poly(2-ethyl-2-oxazoline) fibers in aqueous solutions

    OpenAIRE

    Güner, Pınar Tatar; Miko, Annamaria; Schweinberger, Florian F.; Demirel, A. Levent

    2012-01-01

    Poly(2-ethyl-2-oxazoline) (PEOX) formed self-assembled fibers in aqueous solutions above the cloud point temperature (T-c) through a slow crystallization process. The fiber formation above T-c happened both in pure water and in the presence of salting-in (SCN-) and salting-out (CH3COO-) ions. The crystal structure and the melting temperature of the PEOX fibers were determined.

  12. Ethyl ester production from (RBD palm oil

    Directory of Open Access Journals (Sweden)

    Oscar Mauricio Martínez Ávila

    2010-07-01

    Full Text Available This work develops a methodology for obtaining ethyl esters from RBD (refined, bleached and deodorised palm oil by evaluating the oil’s transesterification and separation. Two catalysts were first tested (KOH and NaOH by studying the effect of water presence on the reaction. The separation process was then evaluated by using water and water-salt and water-acid mixtures, establishing the agent offering the best results and carrying out the purification stage. Raw materials and products were characterised for comparing the latter with those obtained by traditional means and verifying the quality of the esters so produced; minimum differences were found bet-ween both. The proposed methodology thus allows esters to be used as raw material in petrochemical industry applications. A more profitable process can be obtained compared to those used today, given the amounts of separation agent so established (1% H3PO4 solution, in water. The overall process achieved 74.4% yield, based on the oil being used.

  13. Determination of mycotoxin exposure in Germany using an LC-MS/MS multibiomarker approach.

    Science.gov (United States)

    Gerding, Johannes; Cramer, Benedikt; Humpf, Hans-Ulrich

    2014-12-01

    In this study, the exposure of a German population (n = 101) to mycotoxins was assessed using an LC-MS/MS urinary multibiomarker approach. Food consumption of the participants was documented with a food frequency questionnaire to correlate mycotoxin exposure with individual nutritional habits. The presence of 23 urinary biomarkers including trichothecenes (deoxynivalenol (DON), DON-3-glucuronide (DON-3-GlcA), T-2 toxin, HT-2 toxin (HT-2, HT-2-toxin-4-glucuronide (HT-2-GlcA), fumonisins (fumonisin B1, fumonisin B2), aflatoxins (aflatoxin B1, aflatoxin G2, aflatoxin B2, aflatoxin M1), zearalenone and derivatives (zearalanone, α-zearalenol, β-zearalenol, zearalenone-14-O-glucuronide, zearalanone-14-O-glucuronide, α-zearalenol-14-O-glucuronide/β-zearalenol-14-O-glucuronide), ochratoxin A, ochratoxin alpha, enniatin B and dihydrocitrinone was evaluated using a validated, sensitive "dilute and shoot"-LC-MS/MS method applying Scheduled MRM(TM) technology. Six mycotoxins and urinary metabolites were detected (DON, DON-3-GlcA, zearalenone-14-O-glucuronide, T-2 toxin, enniatin B, and dihydrocitrinone) in 87% of the samples in single- or co-occurence. Only DON and DON-3-GlcA were detectable in quantifiable amounts. A provisional mean daily intake of 0.52 μg DON/kg body weight was calculated. No statistical evidence for the correlation of staple food intake and urinary biomarker concentration could be determined. The results of this study suggest a low everyday exposure of the investigated German population to mycotoxins, but reveal peak exposures above the widely accepted tolerable daily intake to DON in parts of the population. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. S-naproxen-ss-1-O-acyl glucuronide degradation kinetic studies by stopped-flow high-performance liquid chromatography-H-1 NMR and high-performance liquid chromatography-UV

    DEFF Research Database (Denmark)

    Mortensen, R. W.; Corcoran, O.; Cornett, Claus

    2001-01-01

    Acyl-migrated isomers of drug beta -1-O-acyl glucuronides have been implicated in drug toxicity because they can bind to proteins. The acyl migration and hydrolysis of S-naproxen-beta -1-O-acyl glucuronide (S-nap-g) was followed by dynamic stopped-flow HPLC-H-1 NMR and HPLC methods. Nine first or...

  15. Phenolic Profile of Potentilla anserina L. (Rosaceae) Herb of Siberian Origin and Development of a Rapid Method for Simultaneous Determination of Major Phenolics in P. anserina Pharmaceutical Products by Microcolumn RP-HPLC-UV

    OpenAIRE

    Olennikov,Daniil N.; Kashchenko, Nina I.; Nadezhda K. Chirikova; Sargylana S. Kuz'mina

    2014-01-01

    A chemical study of Potentilla anserina L. herb (Rosaceae) of Siberian origin led to the isolation of 17 compounds. Three ellagitannins—potentillin, agrimonic acid A and B—are reported for the first time in this species. With a view to rapid quantitative analysis, a new method was developed for simultaneous determination of major phenolic compounds in P. anserina, including caffeic acid, myricetin-3-O-glucuronide, agrimoniin, ellagic acid, miquelianin, isorhamnetin-3-O-glucuronide, and kaempf...

  16. Ultrasound-assisted hydrolysis of conjugated parabens in human urine and their determination by UPLC-MS/MS and UPLC-HRMS.

    Science.gov (United States)

    Schlittenbauer, Linda; Seiwert, Bettina; Reemtsma, Thorsten

    2016-02-01

    Parabens are preservatives widely used in personal care products, pharmaceutical formulations as well as in food, and they are considered endocrine disruptors. For application in biomonitoring studies we developed a method for the determination of eight parabens from human urine. Sample preparation was enhanced and simplified by the combination of ultrasound-assisted enzymatic hydrolysis of conjugates (glucuronide and sulfate) followed by an extraction-free cleanup step. Quantification, using deuterated parabens as internal standards, was performed by ultrahigh-performance liquid chromatography coupled to either triple-quadrupole (UPLC-QqQ) or time-of-flight (UPLC-QqTOF) mass spectrometry. Full chromatographic separation of three butyl paraben isomers was achieved. Limits of quantification for both mass analyzers ranged from 0.1 to 0.5 μg/L for methyl, ethyl, n-/isopropyl, n-/isobutyl, and benzyl paraben in 200 μL of urine sample. The method was tested for applicability and showed high precision (intra- and interday 0.9-14.5%) as well as high accuracy (relative recovery 95-132%). A total of 39 urine samples were analyzed by both mass analyzers. The results agreed well, with a trend to higher deviation at low concentrations (less than 10 μg/L). Methyl, ethyl, and n-propyl paraben were detected most frequently (in more than 87% of the samples) with median concentrations ranging from 0.8 to 16.6 μg/L. Female urine showed higher median concentrations for all parabens, which may indicate higher exposure due to lifestyle. This method permits accurate and high-throughput analysis of parabens for epidemiological studies. Further, the UPLC-QqTOF approach provides additional information on human exposure to other compounds by post-acquisition analysis.

  17. Gilbert syndrome redefined: a complex genetic haplotype influences the regulation of glucuronidation.

    Science.gov (United States)

    Ehmer, Ursula; Kalthoff, Sandra; Fakundiny, Bastian; Pabst, Brigitte; Freiberg, Nicole; Naumann, Ronald; Manns, Michael P; Strassburg, Christian P

    2012-06-01

    Gilbert syndrome (GS) is characterized by intermittent unconjugated hyperbilirubinemia without structural liver damage, affecting about 10% of the white population. In GS the UGT1A1*28 variant reduces bilirubin conjugation by 70% and is associated with irinotecan and protease inhibitor side effects. The aim of this study was to characterize potential in vivo consequences of UGT1A gene variability in GS. Three hundred GS patients (UGT1A1*28 homozygous) and 249 healthy blood donors (HBD) were genotyped for UGT1A (UGT1A1*28, UGT1A3-66 T>C, UGT1A6*3a, UGT1A7*3) and transporter single nucleotide polymorphisms (SNPs) (SCLO1B1 p.V174A, SCLO1B1 p.N130D, ABCC2 p.I1324I, ABCC2-24 UTR) using TaqMan-5'-nuclease-assays. A humanized transgenic UGT1A-SNP and corresponding wildtype mouse model were established carrying the GS-associated UGT1A variant haplotype. UGT1A transcript and protein expression, and transcriptional activation were studied in vivo. Homozygous UGT1A1*28 GS individuals were simultaneously homozygous for UGT1A3-66 T>C (91%), UGT1A6*2a (77%), and UGT1A7*3 (77%). Seventy-six percent of GS and only 9% of HBD were homozygous for the variant haplotype spanning four UGT1A genes. SCLO1B1 and ABCC2 SNPs showed no differences. In transgenic humanized UGT1A SNP and wildtype mice this UGT1A haplotype led to lower UGT1A messenger RNA (mRNA) expression and UGT1A protein synthesis. UGT1A transcriptional activation by dioxin, phenobarbital, and endotoxin was significantly reduced in SNP mice. Our data redefine the genetic basis behind GS. In vivo data studying the genotype present in 76% of GS individuals suggest that transcription and transcriptional activation of glucuronidation genes responsible for conjugation and detoxification is directly affected, leading to lower responsiveness. This study suggests that GS should be considered a potential risk factor for drug toxicity. Copyright © 2011 American Association for the Study of Liver Diseases.

  18. Novel recombinant ethyl ferulate esterase from Burkholderia multivorans

    CSIR Research Space (South Africa)

    Rashamuse, KJ

    2007-11-01

    Full Text Available Isolation and identification of bacterial isolates with specific ferulic acid (FA) esterase activity and cloning of a gene encoding activity. A micro-organism with ethyl ferulate hydrolysing (EFH) activity was isolated by culture enrichment...

  19. Influence of prohexadione-calcium, trinexapac-ethyl and ...

    African Journals Online (AJOL)

    ethyl (TNE) and hexaconazole (HX) on lodging and gibberellin (GA) biosynthesis pathway of rice cultivar, Hwayeongbyeo. It was observed that these novel synthetic growth retardants suppressed lodging of rice under field conditions through ...

  20. Antinociceptive activities of crude methanolic extract and phases, n-butanolic, chloroformic and ethyl acetate from Caulerpa racemosa (Caulerpaceae

    Directory of Open Access Journals (Sweden)

    Everton T. Souza

    Full Text Available In this study, we attempted to identify the possible antinociceptive actions of n-butanolic phase, chloroformic phase, ethyl acetate phase and crude methanolic extract obtained from Caulerpa racemosa. This seaweed is cosmopolitan in world, mainly in tropical regions. The n-butanolic, chloroformic, ethyl acetate phases and crude methanolic extract, all administered orally in the concentration of 100 mg/kg, reduced the nociception produced by acetic acid by 47.39%, 70.51%, 76.11% and 72.24%, respectively. In the hotplate test the chloroformic and ethyl acetate phase were activite in this models. In the neurogenic phase on formalin test, were observed that crude methanolic extract (51.77%, n-butanolic phase (35.12%, chloroformic phase (32.70% and indomethacin (32.06% were effective in inhibit the nociceptive response. In the inflammatory phase, only the ethyl acetate phase (75.43% and indomethacin (47.83% inhibited significantly the nociceptive response. Based on these data, we can infer that the ethyl acetate phase shows a significant anti-inflammatory profile, whose power has not yet been determined. However, pharmacological and chemical studies are continuing in order to characterize the mechanism(s responsible for the antinociceptive action and also to identify other active principles present in Caulerpa racemosa.

  1. Validation of a probe for assessing deconjugation of glucuronide and sulfate phase II metabolites assayed through LC-MS/MS in biological matrices.

    Science.gov (United States)

    Grignon, Claire; Dupuis, Antoine; Albouy-Llaty, Marion; Condylis, Maxime; Barrier, Laurence; Carato, Pascal; Brunet, Bertrand; Migeot, Virginie; Venisse, Nicolas

    2017-09-01

    LC-MS/MS has been proposed in various areas such as Therapeutic Drug Monitoring (TDM), Human Biomonitoring (HBM), disease diagnosis, clinical toxicology and doping control to identify and quantify chemical parents and their metabolites in biological matrices. To determine the total content of a xenobiotic (unconjugated+conjugated forms), an enzymatic hydrolysis step is required. Most studies in the literature have not controlled the effectiveness of the deconjugation process because no method has been described for that purpose. Therefore the aim of this study was to develop and validate a deconjugation probe using a LC-MS/MS method. In order to estimate deconjugation using β-glucuronidase and/or sulfatase, 4-methyl-umbelliferone (MU) and its conjugates were used as markers. Glucuronidase/sulfatase was added to plasma or urine spiked with 4-methylumbelliferyl-β-d-glucuronide (MUG) and 4-methylumbelliferyl sulfate (MUS) and umbelliferone, which was used as the internal standard. After incubation at 37°C during 90min, MU appears as a result of the deconjugation of MUG and MUS. The concentrations of the 3 markers were determined using LC-MS/MS. Trueness and precision of the LC-MS/MS method were determined by quality control analysis at three different levels of concentration covering the whole range of calibration. In both matrices, the analytical method allows quantification of the different compounds, with good linearity, trueness and precision and negligible matrix effects. The method was applied with success to deconjugation assay using active glucuronidase/sulfatase in plasma and urine. The probe developed in this study allows to ensure that enzymatic preparation is working properly in the frame of a quality system. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Fibronectin fixation on poly(ethyl acrylate)-based copolymers.

    Science.gov (United States)

    Briz, N; Antolinos-Turpin, C M; Alió, J; Garagorri, N; Ribelles, J L Gómez; Gómez-Tejedor, J A

    2013-08-01

    The aim of this paper is to quantify the adhered fibronectin (FN; by adsorption and/or grafting) and the exposure of its cell adhesive motifs (RGD and FNIII7-10) on poly(ethyl acrylate) (PEA) copolymers whose chemical composition has been designed to increase wettability and to introduce acid functional groups. FN was adsorbed to PEA, poly(ethyl acrylate-co-hydroxyethyl acrylate), poly(ethyl acrylate-co-acrylic acid), and poly(ethyl acrylate-co-methacrylic acid) copolymers, and covalently cross-linked to poly(ethyl acrylate-co-acrylic acid) and poly(ethyl acrylate-co-methacrylic acid) copolymers. Amount of adhered FN and exhibition of RGD and FNIII7- 10 fragments involved in cell adhesion were quantified with enzyme-linked immunosorbent assay tests. Even copolymers with a lower content of the hydrophilic component showed a decrease in water contact angle. In addition, FN was successfully fixed on all surfaces, especially on the hydrophobic surfaces. However, it was demonstrated that exposure of its cell adhesion sequences, which is the key factor in cell adhesion and proliferation, was higher for hydrophilic surfaces. Copyright © 2013 Wiley Periodicals, Inc.

  3. Extraction, Separation, and Purification of Blueberry Anthocyanin Using Ethyl Alcohol

    Directory of Open Access Journals (Sweden)

    Zhe Gao

    2017-11-01

    Full Text Available Blueberry contains many substances that are important to the human body and can prevent cardiovascular diseases, protect the retina, and soften blood vessels. Anthocyanin, which is extracted from blueberry, can activate the retina, strengthen vision, reduce serum cholesterol, triglyceride and high-density lipoprotein, and protect cell nucleus tissues from radical oxidation; hence, blueberry is of importance to scientists from different countries. In this study, anthocyanin was extracted and separated from blueberry using ethyl alcohol to investigate the effects of factors, such as ethyl alcohol volume ratio on anthocyanin extraction and separation technologies. The extracting solution was then purified using the macroreticular resin purification method to investigate the effects of ethyl alcohol concentration and eluent dosage on anthocyanin extraction during purification. The research results demonstrated that 60 % ethyl alcohol volume fraction, 1 : 10 mass ratio of solid to liquid, and 60 °C ultrasonic temperature were the best conditions for anthocyanin extraction. The best purification conditions were 95 % ethyl alcohol, which had been acidized by 0.3 % hydrochloric acid and 70 ml of eluent. This work provides a reference for the application of ethyl alcohol in anthocyanin extraction.

  4. Ethyl acetate production by the elusive alcohol acetyltransferase from yeast.

    Science.gov (United States)

    Kruis, Aleksander J; Levisson, Mark; Mars, Astrid E; van der Ploeg, Max; Garcés Daza, Fernando; Ellena, Valeria; Kengen, Servé W M; van der Oost, John; Weusthuis, Ruud A

    2017-05-01

    Ethyl acetate is an industrially relevant ester that is currently produced exclusively through unsustainable processes. Many yeasts are able to produce ethyl acetate, but the main responsible enzyme has remained elusive, hampering the engineering of novel production strains. Here we describe the discovery of a new enzyme (Eat1) from the yeast Wickerhamomyces anomalus that resulted in high ethyl acetate production when expressed in Saccharomyces cerevisiae and Escherichia coli. Purified Eat1 showed alcohol acetyltransferase activity with ethanol and acetyl-CoA. Homologs of eat1 are responsible for most ethyl acetate synthesis in known ethyl acetate-producing yeasts, including S. cerevisiae, and are only distantly related to known alcohol acetyltransferases. Eat1 is therefore proposed to compose a novel alcohol acetyltransferase family within the α/β hydrolase superfamily. The discovery of this novel enzyme family is a crucial step towards the development of biobased ethyl acetate production and will also help in selecting improved S. cerevisiae brewing strains. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  5. Assessment of acute oral and dermal toxicity of 2 ethyl-carbamates with activity against Rhipicephalus microplus in rats.

    Science.gov (United States)

    Prado-Ochoa, María Guadalupe; Gutiérrez-Amezquita, Ricardo Alfonso; Abrego-Reyes, Víctor Hugo; Velázquez-Sánchez, Ana María; Muñoz-Guzmán, Marco Antonio; Ramírez-Noguera, Patricia; Angeles, Enrique; Alba-Hurtado, Fernando

    2014-01-01

    The acute oral and dermal toxicity of two new ethyl-carbamates (ethyl-4-bromophenyl-carbamate and ethyl-4-chlorophenyl-carbamate) with ixodicide activity was determined in rats. The oral LD50 of each carbamate was 300 to 2000 mg/kg, and the dermal LD50 of each carbamate was >5000 mg/kg. Clinically, the surviving rats that had received oral doses of each carbamate showed decreased weight gain (P lesions, binucleated hepatocytes, focal coagulative necrosis, and congestion areas; the severity of the lesions increased with dosage. Furthermore, an slight increase in gamma-glutamyltransferase, lactate dehydrogenase, and creatinine was observed in the plasma. The dermal application of the maximum dose (5000 mg/kg) of each carbamate did not cause clinical manifestations or liver and skin alterations. This finding demonstrates that the carbamates under study have a low oral hazard and low acute dermal toxicity.

  6. Headspace solid-phase microextraction of higher fatty acid ethyl esters in white rum aroma.

    Science.gov (United States)

    Pino, J; Martí, M P; Mestres, M; Pérez, J; Busto, O; Guasch, J

    2002-04-19

    Fatty acid ethyl esters are the main components of rum aroma and play an important sensorial impact in these distilled alcoholic beverages. Herein, a method for analysing these volatile compounds is described. It involves a separation and concentration step using headspace solid-phase microextraction and determination by capillary gas chromatography using flame ionisation detection. The influence of different parameters related to the isolation and concentration step, such as ethanol concentration, ionic strength, sample volume, time and temperature of extraction, was studied. The developed method enabled recoveries >91% for the analyzed compounds with limits of detection between 0.007 and 0.027 mg/l, all of them lower than the range of concentrations found in rum samples. The method was successfully applied to the analysis of fatty acid ethyl esters in different commercial white rums.

  7. Ethyl ester purpurine-18 from Gossypium mustelinum (Malvaceae);Feoforbideo (etoxi-purpurina-18) isolado de Gossypium mustelinum (Malvaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Tania Maria Sarmento; Camara, Celso Amorim, E-mail: taniasarmento@dq.ufrpe.b [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Quimica; Barbosa-Filho, Jose Maria [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Lab. de Tecnologia Farmaceutica; Giulietti, Ana Maria [Universidade Estadual de Feira de Santana, BA (Brazil). Dept. de Ciencias Biologicas

    2010-07-01

    The phaeophorbide ethyl ester named Purpurine-18 and the flavonoids quercetin and kaempferol were obtained by chromatographic procedures from the chloroform fraction of aerial parts of Gossypium mustelinum. The structure of these compound was determined by NMR, IR and mass spectra data analysis. This is the first occurrence of this compound in Angiosperm. (author)

  8. Modification and re-validation of the ethyl acetate-based multi-residue method for pesticides in produce

    NARCIS (Netherlands)

    Mol, J.G.J.; Rooseboom, A.; Dam, van R.; Roding, M.; Arondeus, K.; Sunarto, S.

    2007-01-01

    The ethyl acetate-based multi-residue method for determination of pesticide residues in produce has been modified for gas chromatographic (GC) analysis by implementation of dispersive solid-phase extraction (using primary¿secondary amine and graphitized carbon black) and large-volume (20 ¿L)

  9. Modification and re-validation of the ethyl acetate-based multi-residue method for pesticides in produce

    NARCIS (Netherlands)

    Mol, H.G.J.; Rooseboom, A.; Dam, R. van; Roding, M.; Arondeus, K.; Sunarto, S.

    2007-01-01

    The ethyl acetate-based multi-residue method for determination of pesticide residues in produce has been modified for gas chromatographic (GC) analysis by implementation of dispersive solid-phase extraction (using primary-secondary amine and graphitized carbon black) and large-volume (20 μL)

  10. [Iminium compounds against bacteria and fungi. 29. 3-Alkoxymethyl-1-ethyl-, 3-alkylthiomethyl-1-ethyl-, 3-alkoxymethyl-1-butyl-, and 3-alkylthiomethyl-1-butylbenzimidazolium chloride].

    Science.gov (United States)

    Pernak, J; Skrzypczak, A; Michalak, L; Jedraszczyk, J; Krysiński, J; Kazmierczak, M; Mrówczyński, B

    1993-04-01

    Syntheses and antimicrobial activity of 3-alkoxymethyl-1-ethyl-, 3-alkylthiomethyl-1-ethyl-, 3-alkoxymethyl-1-butyl-, and 3-alkylthiomethyl-1-butylbenzimidazolium chlorides are described. The compounds were obtained by reaction of 1-ethyl- or 1-butylbenzimidazole with chloromethylalkyl ethers or chloromethylalkyl sulfide. Antibacterial properties were tested on 13 strains of bacteria and fungi. 3-Dodecylthio-methyl-1-ethyl-benzimidazolium chloride exhibited the highest antibacterial activity.

  11. Effects of thyroid status and thyrostatic drugs on hepatic glucuronidation of lodothyronines and other substrates in rats - Induction of phenol UDP-glucuronyltransferase by methimazole

    NARCIS (Netherlands)

    T.J. Visser (Theo); E. Kaptein (Ellen); A.L. Gijzel (Anthonie); W.W. de Herder (Wouter); M.L. Cannon (Mark); F. Bonthuis (Fred); W.J. de Greef (W.)

    1996-01-01

    textabstractGlucuronidation of iodothyronines in rat liver is catalyzed by at least three UDP-glucuronyltransferases (UGTs): bilirubin UGT, phenol UGT, and androsterone UGT. Bilirubin and phenol UGT activities are regulated by thyroid hormone, but the effect of thyroid status on hepatic

  12. Effects of Ethyl Acetate Extracts from the Polycephalomyces nipponicus Isolate Cod-MK1201 (Ascomycetes) against Human Pathogenic Bacteria and a Breast Cancer Cell Line.

    Science.gov (United States)

    Sangdee, Kusavadee; Seephonkai, Prapairat; Buranrat, Benjaporn; Surapong, Nilawan; Sangdee, Aphidech

    2016-01-01

    This study aimed to identify a suitable organic solvent for extracting bioactive compounds from Polycephalomyces nipponicus and to evaluate the antibacterial and anticancer activities of the extracts obtained. Only extracts obtained with ethyl acetate exhibited antibacterial activity, so ethyl acetate was chosen for large-scale extraction. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Gram-positive and Gram-negative human pathogenic bacteria of the 3 ethyl acetate-derived extracts-ethyl acetate extract from P. nipponicus (PN-ME), ethyl acetate extract after defatting (PN-ME*), and ethyl acetate extract after refluxation (PN-ME')-were determined. PN-ME' exhibited the most potent activity, inhibiting 12 of the 18 test bacteria, especially Bacillus cereus ATCC 11778 and Vibrio cholera (O1) DMST 9700, with low MIC and MBC values. PN-ME* showed greater inhibitory activity than PN-ME. The effects of the extracts on bacterial cell morphology were also determined. After 120 minutes of treatment with PN-ME* or PN-ME', B. cereus ATCC 11778 exhibited an abnormal rod-shaped cell structure, with some cells elongated to multiple times their original size and others appearing collapsed. V cholera (O1) DMST 9700 cells showed shrinkage and the formed subsurface cavities. PN-ME* and PN-ME' also inhibited the growth of MCF-7 breast cancer cells. In conclusion, the fungal isolate P. nipponicus Cod-MK1201 represents a source of antibacterial and anti-breast cancer compounds.

  13. Identification of Uridine 5'-Diphosphate-Glucuronosyltransferases Responsible for the Glucuronidation of Mirabegron, a Potent and Selective β3-Adrenoceptor Agonist, in Human Liver Microsomes.

    Science.gov (United States)

    Konishi, Kentaro; Tenmizu, Daisuke; Takusagawa, Shin

    2017-11-21

    Mirabegron is cleared by multiple mechanisms, including drug-metabolizing enzymes. One of the most important clearance pathways is direct glucuronidation. In humans, M11 (O-glucuronide), M13 (carbamoyl-glucuronide), and M14 (N-glucuronide) have been identified, of which M11 is one of the major metabolites in human plasma. The objective of this study was to identify the uridine 5'-diphosphate (UDP)-glucuronosyltransferase (UGT) isoform responsible for the direct glucuronidation of mirabegron using human liver microsomes (HLMs) and recombinant human UGTs (rhUGTs). Reaction mixtures contained 1-1000 μM mirabegron, 8 mM MgCl2, alamethicin (25 μg/mL), 50 mM Tris-HCl buffer (pH 7.5), human liver microsome (HLM) or rhUGT (1.0 mg protein/mL), and 2 mM UDP-glucuronic acid in a total volume of 200 μL for 120 min at 37 °C. HLMs from 16 individuals were used for the correlation study, and mefenamic acid and propofol were used for the inhibition study. Regarding M11 formation, rhUGT2B7 showed high activity among the rhUGTs tested (11.3 pmol/min/mg protein). This result was supported by the correlation between M11 formation activity and UGT2B7 marker enzyme activity (3-glucuronidation of morphine, r 2 = 0.330, p = 0.020) in individual HLMs; inhibition by mefenamic acid in pooled HLMs (IC50 = 22.8 μM); and relatively similar K m values between pooled HLMs and rhUGT2B7 (1260 vs. 486 μM). Regarding M13 and M14 formation, rhUGT1A3 and rhUGT1A8 showed high activity among the rhUGTs tested, respectively. UGT2B7 is the main catalyst of M11 formation in HLMs. Regarding M13 and M14 formation, UGT1A3 and UGT1A8 are strong candidates for glucuronidation, respectively.

  14. Effect of icosapent ethyl (eicosapentaenoic acid ethyl ester) on omeprazole plasma pharmacokinetics in healthy adults.

    Science.gov (United States)

    Braeckman, Rene A; Stirtan, William G; Soni, Paresh N

    2014-09-01

    Icosapent ethyl (IPE) is a high-purity prescription form of eicosapentaenoic acid ethyl ester approved by the US Food and Drug Administration as an adjunct to diet to reduce triglyceride levels in adult patients with severe hypertriglyceridemia. Patients with high serum triglycerides may be taking concurrent medications for associated conditions such as obesity and/or diabetes mellitus. To evaluate the effect of IPE on the plasma pharmacokinetics (PK) of omeprazole, a commonly used proton pump inhibitor and a substrate of cytochrome P450 (CYP) 2C19. Omeprazole (40 mg/day for 7 days) was administered orally without and with 4 g/day IPE at steady state. The primary PK endpoint was area under the concentration-time curve from time 0 to 24 h (AUC0-24); secondary endpoints included maximum observed plasma concentration (C max). Safety was monitored in all subjects who received one or more dose(s) of the study drug. Thirty healthy adult subjects were enrolled and 28 completed the study. IPE 4 g/day at steady state did not significantly change the AUC0-24 or C max of omeprazole when co-administered at 40 mg/day to steady state. The ratios of least squares geometric means (90 % confidence interval) for AUC0-24 and C max (omeprazole with IPE vs. omeprazole alone) were 0.84 (76.0-91.9) and 1.01 (87.4-116.3), respectively. There were no clinically significant findings from laboratory tests, vital signs, or physical examinations. At steady-state concentrations, IPE 4 g/day did not inhibit the AUC0-24 or C max of omeprazole 40 mg/day, a CYP2C19 substrate. Co-administration of IPE with omeprazole was safe and well tolerated.

  15. Theoretical study for OH radical-initiated atmospheric oxidation of ethyl acrylate.

    Science.gov (United States)

    Sun, Yanhui; Zhang, Qingzhu; Hu, Jingtian; Chen, Jianmin; Wang, Wenxing

    2015-01-01

    OH radical-initiated atmospheric oxidation of ethyl acrylate (ethyl 2-propenoate, EA) has been investigated by performing density functional theory (DFT) calculations. Optimizations of the reactants, intermediates, transition states and products were carried out at the MPWB1K/6-31+G(d,p) level. Single-point energy calculations were performed at the MPWB1K/6-311+G(3df,2p) level of theory. The detailed oxidation mechanism was presented and discussed. The results show that the OH addition is more energetically favorable than the H abstraction. Rice-Ramsperger-Kassel-Marcus (RRKM) theory was used to predict the rate constants over the possible atmospheric temperature range of 180-370 K. The Arrhenius expression adequately describes the total rate constant: k(EA+OH)=(1.71×10(-12))exp(805.42/T)cm(3) molecule(-1) s(-1). At 298 K, the atmospheric lifetime of ethyl acrylate determined by OH radicals is about 16.2h. In order to find out the effect of alkyl substitution on the reaction activity, rate constants for the reactions of methyl acrylate, methyl methacrylate and butyl acrylate with OH radicals were also discussed. Calculation results show that the reaction activity may increase with the increased electron-donating substitution for electrophilic addition reaction. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Chemodynamics of methyl parathion and ethyl parathion: adsorption models for sustainable agriculture.

    Science.gov (United States)

    Tabassum, Noshabah; Rafique, Uzaira; Balkhair, Khaled S; Ashraf, Muhammad Aqeel

    2014-01-01

    The toxicity of organophosphate insecticides for nontarget organism has been the subject of extensive research for sustainable agriculture. Pakistan has banned the use of methyl/ethyl parathions, but they are still illegally used. The present study is an attempt to estimate the residual concentration and to suggest remedial solution of adsorption by different types of soils collected and characterized for physicochemical parameters. Sorption of pesticides in soil or other porous media is an important process regulating pesticide transport and degradation. The percentage removal of methyl parathion and ethyl parathion was determined through UV-Visible spectrophotometer at 276 nm and 277 nm, respectively. The results indicate that agricultural soil as compared to barren soil is more efficient adsorbent for both insecticides, at optimum batch condition of pH 7. The equilibrium between adsorbate and adsorbent was attained in 12 hours. Methyl parathion is removed more efficiently (by seven orders of magnitude) than ethyl parathion. It may be attributed to more available binding sites and less steric hindrance of methyl parathion. Adsorption kinetics indicates that a good correlation exists between distribution coefficient (Kd) and soil organic carbon. A general increase in Kd is noted with increase in induced concentration due to the formation of bound or aged residue.

  17. [Photonic Efficiency of Ethyl Acetate Photolysis in Gas Phase: Dependence on Wavelength and Catalyst].

    Science.gov (United States)

    Fang, Xue-hui; Zhao, Jie; Shu, Li; Gao, Yong; Ye, Zhao-lian

    2015-06-01

    Four kinds of excilamps with different wavelengths (XeCl*, KrCl*, XeBr* and KrBr*) were used for removing ethyl acetate in gas phase. The removal efficiencies of ethyl acetate by three loaded catalysts (TiO2 loaded on organic film, graphene loaded on organic film, and TiO2 loaded on mesh) were compared, and the effects of lamp sources, irradiation power and initial concentration on the removal efficiency were also investigated. Moreover, irradiation spectra and power of light sources were determined, and photonic efficiencies under different reaction conditions were calculated. The experimental results showed that the removal efficiency of ethyl acetate decreased in the order of KrBr* > KrCl* > XeCl* > XeBr*, while the photonic efficiency seemed to be relatively high with both XeCl* and KrBr* excilamps. In the presence of the catalyst of TiO2 loaded on organic film, both the removal efficiency and the photonic efficiency were higher than those without catalyst, but the increment was not significant. The photonic efficiency increased with increasing initial concentration and gas flow rate. With KrBr* excilamp, a photonic efficiency of 5.63% was obtained when the experimental conditions were set as: irradiation power of 0.76 W, initial concentration of 946 mg x m(-3), and gas flow rate of 600 mL x min(-1).

  18. Chemodynamics of Methyl Parathion and Ethyl Parathion: Adsorption Models for Sustainable Agriculture

    Science.gov (United States)

    Rafique, Uzaira; Balkhair, Khaled S.; Ashraf, Muhammad Aqeel

    2014-01-01

    The toxicity of organophosphate insecticides for nontarget organism has been the subject of extensive research for sustainable agriculture. Pakistan has banned the use of methyl/ethyl parathions, but they are still illegally used. The present study is an attempt to estimate the residual concentration and to suggest remedial solution of adsorption by different types of soils collected and characterized for physicochemical parameters. Sorption of pesticides in soil or other porous media is an important process regulating pesticide transport and degradation. The percentage removal of methyl parathion and ethyl parathion was determined through UV-Visible spectrophotometer at 276 nm and 277 nm, respectively. The results indicate that agricultural soil as compared to barren soil is more efficient adsorbent for both insecticides, at optimum batch condition of pH 7. The equilibrium between adsorbate and adsorbent was attained in 12 hours. Methyl parathion is removed more efficiently (by seven orders of magnitude) than ethyl parathion. It may be attributed to more available binding sites and less steric hindrance of methyl parathion. Adsorption kinetics indicates that a good correlation exists between distribution coefficient (Kd) and soil organic carbon. A general increase in Kd is noted with increase in induced concentration due to the formation of bound or aged residue. PMID:24689059

  19. Spectroscopy reveals that ethyl esters interact with proteins in wine.

    Science.gov (United States)

    Di Gaspero, Mattia; Ruzza, Paolo; Hussain, Rohanah; Vincenzi, Simone; Biondi, Barbara; Gazzola, Diana; Siligardi, Giuliano; Curioni, Andrea

    2017-02-15

    Impairment of wine aroma after vinification is frequently associated to bentonite treatments and this can be the result of protein removal, as recently demonstrated for ethyl esters. To evaluate the existence of an interaction between wine proteins and ethyl esters, the effects induced by these fermentative aroma compounds on the secondary structure and stability of VVTL1, a Thaumatin-like protein purified from wine, was analyzed by Synchrotron Radiation Circular Dichroism (SRCD) spectroscopy. The secondary structure of wine VVTL1 was not strongly affected by the presence of selected ethyl esters. In contrast, VVTL1 stability was slightly increased by the addition of ethyl-octanoate, -decanoate and -dodecanoate, but decreased by ethyl-hexanoate. This indicates the existence of an interaction between VVTL1 and at least some aroma compounds produced during fermentation. The data suggest that proteins removal from wine by bentonite can result in indirect removal of at least some aroma compounds associated with them. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Investigation of a recently detected 11-nor-9-carboxy-Δ(9)-tetrahydrocannabinol isomer: Studies on the degradation of 11-nor-9-carboxy-Δ(9)-tetrahydrocannabinol glucuronide.

    Science.gov (United States)

    Hanisch, Stephanie; Paulke, Alexander; Toennes, Stefan W

    2016-09-10

    An isomer of the tetrahydrocannabinol (THC) metabolite 11-nor-9-carboxy-Δ(9)-THC (THCCOOH) had been detected in blood of cannabis users. The present study was initiated to elucidate whether the labile metabolite THCCOOH-glucuronide could be the precursor. THCCOOH-glucuronide was incubated in human serum and albumin (HSA) solution at various temperatures (-18, 4.5, 22 and 37°C) and pH values (pH 7.4 and 8.3) for seven days in the presence or absence of the esterase inhibitor sodium fluoride. Analysis of incubation samples was performed using LC-MS/MS. Marked degradation of THCCOOH-glucuronide was observed at 37°C. It was found that not only THCCOOH, but also the isomer is a degradation product of THCCOOH-glucuronide and its in-vivo production is assumed. Degradation to THCCOOH and the isomer occurred at alkaline pH, in the presence of fluoride-sensitive esterases and of HSA alone. To inhibit isomer formation during sample storage, refrigeration and controlling of the pH are recommended. However, THCCOOH and the isomer exhibit similar properties during incubations in serum, but differ in their interaction with HSA. The present study confirmed the nature of the isomer as degradation product of the abundant THC metabolite THCCOOH-glucuronide. Serum albumin and esterases are obviously involved. The isomer is formed not only during storage, but also under physiological conditions, suggesting that it can be considered an in-vivo metabolite. However, the chemical structure of the isomer remains unknown and further research is necessary. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Determination of Duloxetine and Its Major Metabolites in Rabbit Plasma by High-Performance Liquid Chromatography

    OpenAIRE

    T. K. Laha; S. Sen; G. Mishra

    2015-01-01

    A rapid and sensitive high performance liquid chromatographic method is described for simultaneous determination of duloxetine and its major metabolites, such as 4- hydroxy duloxetine (M7), Glucuronide conjugate of 5-hydroxy-6-methoxy duloxetine (M6) and Glucuronide conjugate of dihydrodiol duloxetine (M12) in rabbit plasma. HPLC analysis was carried out on a µ-Bondapak C18 column (250 mm × 4.6 mm, 5µm particle size) using methanol: phosphate buffer (pH 7.9, 50 mM) (7:3 v/v) as the mobile pha...

  2. Unimolecular Gas-Phase Thermolysis of Ethyl Acetate

    DEFF Research Database (Denmark)

    Egsgaard, Helge; Carlsen, Lars

    1983-01-01

    The unimolecular gas-phase thermolysis of ethyl acetate has been investigated by the Flash-Vacuum-Thermolysis/Field-Ionization Mass Spectrometry (FVT/FI-MS) method in combination with Collision Activation (CA) mass spectrometry at 1253K. Two predominant reactions are observed: elimination...... of ethylene affording acetic acid, the latter to some extent consecutively yielding ketene, and intramolecular oxygen to oxygen ethyl group migration. Additionally minor amounts of acetaldehyde is formed. The mechanistic aspects are discussed based on 18O and 18O/ 13C labelling....

  3. Lipopolysaccharide enhances the cytotoxicity of 2-chloroethyl ethyl sulfide

    Directory of Open Access Journals (Sweden)

    Qui Min

    2003-01-01

    Full Text Available Abstract Background The bacterial endotoxin, lipopolysaccharide (LPS, is a well-characterized inflammatory factor found in the cell wall of Gram-negative bacteria. In this investigation, we studied the cytotoxic interaction between 2-chloroethyl ethyl sulfide (CEES or ClCH2CH2SCH2CH3 and LPS using murine RAW264.7 macrophages. CEES is a sulfur vesicating agent and is an analog of 2,2'-dichlorodiethyl sulfide (sulfur mustard. LPS is a ubiquitous natural agent found in the environment. The ability of LPS and other inflammatory agents (such as TNF-alpha and IL-1beta to modulate the toxicity of CEES is likely to be an important factor in the design of effective treatments. Results RAW 264.7 macrophages stimulated with LPS were found to be more susceptible to the cytotoxic effect of CEES than unstimulated macrophages. Very low levels of LPS (20 ng/ml dramatically enhanced the toxicity of CEES at concentrations greater than 400 μM. The cytotoxic interaction between LPS and CEES reached a maximum 12 hours after exposure. In addition, we found that tumor necrosis factor-alpha (TNF-alpha and interleukin-1-beta (IL-1-beta as well as phorbol myristate acetate (PMA also enhanced the cytotoxic effects of CEES but to a lesser extent than LPS. Conclusion Our in vitro results suggest the possibility that LPS and inflammatory cytokines could enhance the toxicity of sulfur mustard. Since LPS is a ubiquitous agent in the natural environment, its presence is likely to be an important variable influencing the cytotoxicity of sulfur mustard toxicity. We have initiated further experiments to determine the molecular mechanism whereby the inflammatory process influences sulfur mustard cytotoxicity.

  4. Lipopolysaccharide enhances the cytotoxicity of 2-chloroethyl ethyl sulfide.

    Science.gov (United States)

    Stone, William L; Qui, Min; Smith, Milton

    2003-01-06

    The bacterial endotoxin, lipopolysaccharide (LPS), is a well-characterized inflammatory factor found in the cell wall of Gram-negative bacteria. In this investigation, we studied the cytotoxic interaction between 2-chloroethyl ethyl sulfide (CEES or ClCH2CH2SCH2CH3) and LPS using murine RAW264.7 macrophages. CEES is a sulfur vesicating agent and is an analog of 2,2'-dichlorodiethyl sulfide (sulfur mustard). LPS is a ubiquitous natural agent found in the environment. The ability of LPS and other inflammatory agents (such as TNF-alpha and IL-1beta) to modulate the toxicity of CEES is likely to be an important factor in the design of effective treatments. RAW 264.7 macrophages stimulated with LPS were found to be more susceptible to the cytotoxic effect of CEES than unstimulated macrophages. Very low levels of LPS (20 ng/ml) dramatically enhanced the toxicity of CEES at concentrations greater than 400 microM. The cytotoxic interaction between LPS and CEES reached a maximum 12 hours after exposure. In addition, we found that tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1-beta) as well as phorbol myristate acetate (PMA) also enhanced the cytotoxic effects of CEES but to a lesser extent than LPS. Our in vitro results suggest the possibility that LPS and inflammatory cytokines could enhance the toxicity of sulfur mustard. Since LPS is a ubiquitous agent in the natural environment, its presence is likely to be an important variable influencing the cytotoxicity of sulfur mustard toxicity. We have initiated further experiments to determine the molecular mechanism whereby the inflammatory process influences sulfur mustard cytotoxicity.

  5. Antibacterial Activity of Ethyl Acetate the Extract of Noni Fruit (Morinda citrifolia L.) Against Bacterial Spoilage in Fish

    Science.gov (United States)

    Nugraheni, E. R.; Adriani, G. R.; Munawaroh, H.

    2017-04-01

    Noni fruit (Morinda citrifolia L.) contains compounds that have potential as antibacterial agent. Antibacterial compounds produced noni fruit (M. citrifolia L.) can inhibit bacterial growth. This study was conducted to test the antibacterial activity of ethyl acetate extract of noni fruit (M. citrifolia L.) against spoilage bacterial in fish. Pseudomonas aeruginosa, Bacillus cereus, Escherichia coli, Klebsiella oxytoca, and Enterobacter aerogenes isolates and examine antibacterial phytochemical profile. Extraction of noni compounds was done by maceration, followed by partition with ethyl acetate to obtain the soluble and insoluble ethyl acetate fraction. Previews result show that the ethyl acetate extract had very strong activity. Extraction process continued by separation and isolation used preparative thin layer chromatography method, so that obtained five isolates and mark them as A, B, C, D and E. Antibacterial activity assay performed on isolates A, B, C, D, and E with 20 and 30% concentration. The test results showed that isolates A could not be inhibit the growth of bacteria, isolates B, C, D, and E has antibacterial activity with weak to strong inhibition. Isolate B had the greatest inhibition activity against the B. cereus, whereas isolates E had the greatest inhibition activity against P. aeroginosa. MIC (Minimum Inhibitor Concentration) and MBC (Minimum Bactericidal Concentration) test result showed that MIC and MBC values could not be determined. Analysis of compounds by TLC showed that isolate B suspected contains coumarin or flavonoids compounds that have antibacterial activity.

  6. Two new Ni(II) supramolecular complexes based on ethyl isonicotinate and ethyl nicotinate for removal of acid blue 92 dye

    Science.gov (United States)

    Etaiw, Safaa El-din H.; Marie, Hassan

    2018-03-01

    Two new luminescent supramolecular complexes (SC); [Ni(EIN)4(NCS)2] SC1 and [Ni2(EN)8(NCS)4] SC2, (EIN = ethyl isonicotinate, EN = ethyl nicotinate), have been synthesized by self-assembly method and structurally characterized by X-ray single crystal, FT-IR and UV-Vis spectra, PXRD, elemental and thermogravimetric analyses. Both SC1 and SC2 are monoclinic crystals however, they have different asymmetric units. Ni(II) atoms in both SC are isostructural and have similar hexa-coordinate environment. The structures of SC1 and SC2 consist of parallel polymeric 1D-chains, extended in two and three dimensional supramolecular frameworks by intermolecular hydrogen bonding interactions. SC1 and SC2 are luminescent materials which can be used in applications as molecular sensing systems. SC1 and SC2 were used as heterogeneous catalysts for degradation of acid blue 92 (AB-92) under sun light irradiation. The fluorescence measurements of terephthalic acid technique as a probe molecule were used to determine the •OH radicals. Also the radicals trapping experiments using isopropanol alcohol (IPA) as radical scavenger were discussed. In addition a mechanism of degradation was proposed and discussed.

  7. Antimicrobial activity of ethyl acetate extract of Citrullus lanatus seeds

    African Journals Online (AJOL)

    Original Research Article. Antimicrobial activity of ethyl acetate extract of Citrullus lanatus seeds. Upe Francisca Babaiwa1, Osayemwenre Erharuyi2, Abiodun Falodun2 and John. O Akerele1. 1Department of Pharmaceutical Microbiology, Faculty of Pharmacy, University of Benin, Benin City Nigeria, 2Department of.

  8. SYNTHESIS OF FATTY ACID ETHYL ESTER FROM CHICKEN FAT ...

    African Journals Online (AJOL)

    The synthesis of fatty acid ethyl ester from chicken fat waste using ZnO/SiO2 heterogeneous catalyst was carried out using two-step procedures of acid pretreatment by esterification and transesterification of the pretreated oil. The first step reduces the high free fatty acid in the oil to an acceptable level for transesterification ...

  9. Kinetics of Ethyl Acetate Synthesis Catalyzed by Acidic Resins

    Science.gov (United States)

    Antunes, Bruno M.; Cardoso, Simao P.; Silva, Carlos M.; Portugal, Ines

    2011-01-01

    A low-cost experiment to carry out the second-order reversible reaction of acetic acid esterification with ethanol to produce ethyl acetate is presented to illustrate concepts of kinetics and reactor modeling. The reaction is performed in a batch reactor, and the acetic acid concentration is measured by acid-base titration versus time. The…

  10. Glucolipid from the ethyl acetate fraction of Acalypha wilkesiana var ...

    African Journals Online (AJOL)

    Plant recipes are classified as medicinal when the biological activities of compounds obtained from them have been scientifically established. Before now, three compounds namely, ethyl gallate, pyrogallol and D-arabino-hex-1- enitol-1, 5-anhydro-2-deoxy have been isolated from the butanol fraction of Acalypha ...

  11. (Z-Ethyl 2-(3-nitrobenzylidene-3-oxobutanoate

    Directory of Open Access Journals (Sweden)

    Xiaopeng Shi

    2008-12-01

    Full Text Available The title molecule, C13H13NO5, adopts a Z conformation at the C= C double bond. The ethoxy atoms of the ethyl ester group are disordered over two orientations in a 3:2 ratio. Weak intermolecular C—H...O hydrogen bonds help to establish the packing.

  12. Synthesis of Ethyl Nalidixate: A Medicinal Chemistry Experiment

    Science.gov (United States)

    Leslie, Ray; Leeb, Elaine; Smith, Robert B.

    2012-01-01

    A series of laboratory experiments that complement a medicinal chemistry lecture course in drug design and development have been developed. The synthesis of ethyl nalidixate covers three separate experimental procedures, all of which can be completed in three, standard three-hour lab classes and incorporate aspects of green chemistry such as…

  13. The ototoxic effects of ethyl benzene in rats

    NARCIS (Netherlands)

    Cappaert, N.L.M.; Klis, S.F.L.; Muijser, H.; Groot, J.C.M.J. de; Kulig, B.M.; Smoorenburg, G.F.

    1999-01-01

    Exposure to organic solvents has been shown to be ototoxic in animals and there is evidence that these solvents can induce hearing loss in humans. In this study, the effects of inhalation of the possibly ototoxic solvent ethyl benzene on the cochlear function and morphology were evaluated using

  14. Hypolipidemic activity of ethyl acetate fraction of methanolic seed ...

    African Journals Online (AJOL)

    Parts of Persea americana Mill are used for various ethnomedicinal purposes. The aqueous seed extract is used locally by herbalists for the treatment of hyperlipidemia. In this study, our objective was to investigate the possible hypolipidemic effect of ethyl acetate fraction (EAF) of the methanolic seed extract on olive oil- ...

  15. Antidiabetic and Antioxidant Activities of Ethyl Acetate Extract of ...

    African Journals Online (AJOL)

    ... that ethyl acetate extract of T. superba lowers blood glucose and hyperlipidemia, prevents oxidative stress and reduces blood pressure in diabetic conditions, thus justify its traditional use for the management of diabetes and hypertension. Keywords: Antidiabetic, antioxidant, streptozotocin-nicotinamide induced diabetes, ...

  16. The synthesis of fatty acid ethyl ester by carboxylester lipase.

    Science.gov (United States)

    Tsujita, T; Okuda, H

    1994-08-15

    Carboxylester lipase obtained from pig pancreas is associated with fatty acid ethyl ester synthase as judged by their elution in the same fraction from a heparin-Sepharose column, coprecipitations by antibody against purified carboxylester lipase and identical profiles of inhibition by diisopropyl fluorophosphate. Only one polypeptide of molecular mass 74-kDa in purified carboxylester lipase was labeled by immunostaining and affinity labeling with [3H]diisopropyl fluorosphate. Bovine serum albumin decreased the fatty-acid-ethyl-ester-synthesizing activity in a concentration-dependent manner. On incubation of purified carboxylester lipase with trioleylglycerol in an ethanol/water mixture, fatty acid ethyl ester was formed in the presence of a high concentration of bovine serum albumin. The acyltransfer activities from trioleylglycerol to ethanol (ethanolysis) were approximately 25-30 times higher than the acyltransfer activities to water (hydrolysis). When cholesterol was used as an acceptor, acyltransfer activity from trioleylglycerol to cholesterol (cholesterolysis) was also observed. We propose the following mechanism of fatty acid ethyl ester formation from triacyl glycerol. The enzyme attacks triacyl glycerol forming an acyl-enzyme intermediate, and during the deacylation process, alcohol binds to fatty acid as an acceptor. These results suggest that during lipid (triacyl glycerol) degradation, carboxylester lipase contributes to non-oxidative ethanol metabolism in the intestinal lumen.

  17. Ethyl Alcohol Extract of Hizikia fusiforme Induces Caspase ...

    African Journals Online (AJOL)

    Ethyl Alcohol Extract of Hizikia fusiforme Induces Caspase-dependent Apoptosis in Human Leukemia U937 Cells by Generation of Reactive Oxygen Species. C-H Kang, S-H Kang, S-H Boo, S-Y Park, D-O Moon, G-Y Kim ...

  18. Testing pelargonic acid and pyraflufen-ethyl with glyphosate as ...

    African Journals Online (AJOL)

    Testing pelargonic acid and pyraflufen-ethyl with glyphosate as alternatives to paraquat dichloride for the preparation of fire-break tracer lines at Underberg, ... With the exception of Guild (at 0.5 l ha−1), the other herbicides at the rates tested either did not provide effective initial control of the vegetation or they killed the ...

  19. Effects of ethyl acetate leaf extracts of Vitex simplicifolia on ...

    African Journals Online (AJOL)

    The effects of oral administration of ethyl acetate leaf extract of Vitex simplicifolia on vitamins A, E and C, Superoxide dismutase (SOD) and lipid profile levels in alloxan induced diabetic Wistar rats were investigated. The study was conducted with 30 Wistar rats, assigned into six groups of five rats each, and daily ...

  20. Electrical transport in ethyl cellulose–chloranil system

    Indian Academy of Sciences (India)

    Abstract. The charge-transport behaviour in pure and chloranil (Chl) doped ethyl cellulose (EC) system has been studied by measuring the dependence of current on field, temperature, electrode material and dopant con- centration. The role of doping molecular concentration in the polymer matrix and modification in the ...

  1. Radio-sensitizing effect of ethyl caffeate on nasopharyngeal ...

    African Journals Online (AJOL)

    Keywords: Ethyl caffeate, Radio-sensitizing effects, Caspase, Nasopharyngeal carcinoma, CNE-2 cell line, β- .... Data are expressed as mean ± standard .... apoptotic proteins. Previous studies indicated that caspase-9, the initiating protein in caspase cascade reaction, is activated by cytochrome c, and in turn, the activated ...

  2. EFFECTS OF ETHYL ACETATE LEAF EXTRACTS OF Vitex ...

    African Journals Online (AJOL)

    pc

    2017-06-01

    Jun 1, 2017 ... ABSTRACT. The effects of oral administration of ethyl acetate leaf extract of Vitex simplicifolia on vitamins A, E and C, Superoxide dismutase (SOD) and lipid profile levels in alloxan induced diabetic Wistar rats were investigated. The study was conducted with 30 Wistar rats, assigned into six groups of five.

  3. Antisecretory and antiulcerative effects of ethyl acetate fraction of ...

    African Journals Online (AJOL)

    The present work was carried out to investigate the possible effects of ethyl acetate seed fraction of Nigella sativa on gastric ulcers and basal gastric secretions using the Non-Steroidal Anti-inflammatory Drug-induced (NSAID) model. Phytochemical screening according to Trease and Evans, 2002 and acute toxicity tests ...

  4. Effects of Piliostigma thonningii ethyl acetate leaf extract on ...

    African Journals Online (AJOL)

    Recent research findings extol the medicinal significance of the different parts of Piliostigma thonningii. The present study investigated the hepatoprotective effect of its ethyl acetate leaf extract against AlCl3-induced hepatocellular derangement in mature male rats. Thirty male Wistar rats (mean weight, 207 ± 11.01g) were ...

  5. 77 FR 26456 - Carfentrazone-ethyl; Pesticide Tolerances

    Science.gov (United States)

    2012-05-04

    ... proposed mode of action of carfentrazone-ethyl in target plants is through inhibition of the enzyme... enzyme in heme biosynthesis and its inhibition can lead toxic effects where heme is utilized (e.g., red... the rat. Subchronic toxicity studies in rats, mice, and dogs demonstrated that the primary effects...

  6. Catalytic Synthesis of Ethyl Ester From Some Common Oils ...

    African Journals Online (AJOL)

    Catalytic conversion of ethanol to fatty acid ethyl esters (FAEE) was carried out by homogeneous and heterogeneous transesterification of melon seed, shea butter and neem seed oils using NaOH, KOH and 5wt%CaO/Al2O3 catalyst systems respectively. Oil content of the seeds from n-hexane or hot water extract ranged ...

  7. 5α-Androst-16-en-3α-ol β-D-glucuronide, precursor of 5α-androst-16-en-3α-ol in human sweat.

    Science.gov (United States)

    Starkenmann, Christian; Mayenzet, Fabienne; Brauchli, Robert; Troccaz, Myriam

    2013-12-01

    5α-Androst-16-en-3α-ol (α-androstenol) is an important contributor to human axilla sweat odor. It is assumed that α-andostenol is excreted from the apocrine glands via a H2 O-soluble conjugate, and this precursor was formally characterized in this study for the first time in human sweat. The possible H2 O-soluble precursors, sulfate and glucuronide derivatives, were synthesized as analytical standards, i.e., α-androstenol, β-androstenol sulfates, 5α-androsta-5,16-dien-3β-ol (β-androstadienol) sulfate, α-androstenol β-glucuronide, α-androstenol α-glucuronide, β-androstadienol β-glucuronide, and α-androstenol β-glucuronide furanose. The occurrence of α-androstenol β-glucuronide was established by ultra performance liquid chromatography (UPLC)/MS (heated electrospray ionization (HESI)) in negative-ion mode in pooled human sweat, containing eccrine and apocrine secretions and collected from 25 female and 24 male underarms. Its concentration was of 79 ng/ml in female secretions and 241 ng/ml in male secretions. The release of α-androstenol was observed after incubation of the sterile human sweat or α-androstenol β-glucuronide with a commercial glucuronidase enzyme, the urine-isolated bacteria Streptococcus agalactiae, and the skin bacteria Staphylococcus warneri DSM 20316, Staphylococcus haemolyticus DSM 20263, and Propionibacterium acnes ATCC 6919, reported to have β-glucuronidase activities. We demonstrated that if α- and β-androstenols and androstadienol sulfates were present in human sweat, their concentrations would be too low to be considered as potential precursors of malodors; therefore, the H2 O-soluble precursor of α-androstenol in apocrine secretion should be a β-glucuronide. Copyright © 2013 Verlag Helvetica Chimica Acta AG, Zürich.

  8. Ethyl p-methoxycinnamate from Kaempferia galanga inhibits angiogenesis through tyrosine kinase

    Directory of Open Access Journals (Sweden)

    Juni Ekowati

    2015-04-01

    Full Text Available Background Many tumors express on their receptor tyrosine kinases vascular endothelial growth factor activity associated with angiogenesis. Inhibition of angiogenesis through reduction of tyrosine kinase activity is a promising strategy for cancer therapy. The present study aimed to determine the mechanism and potency of ethyl p-methoxycinnamate (EPMC isolated from Kaempferia galanga as angiogenesis inhibitor. Methods A laboratory experimental study was conducted using chorio-allantoic membranes (CAMs of nine-day old chicken eggs induced by 60ng basic fibroblast growth factor (bFGF. Ethyl p-methoxycinnamate (EPMC potency was determined at dosages of 30, 60, 90 and 120 mg and compared with celecoxib 60 mg as reference drug and one negative bFGF-induced control group. Neovascularization and endothelial cell count in CAM blood vessels were evaluated. To predict the antiangiogenic mechanism of EPMC, a docking study was performed with the Molegro Virtual Docker program on tyrosine kinase as receptor (PDB 1XKK. Results Angiogenesis stimulation by bFGF was prevented significantly (p<0.05 by EPMC at dosages of 30, 60, 90 and 120 mg and this activity was dose dependent. Molecular docking showed interaction between EPMC functional groups and tyrosine kinase amino acids at Met766, Met793, Thr854, Thr790, Gln791 and Ala743. There was an association between EPMC antiangiogenic activity and docking study results. Conclusions Ethyl p-methoxycinnamate is a potential new angiogenesis inhibitor through interaction with tyrosine kinase. EPMC could be a promising therapeutic agent for treatment of angiogenesis-related diseases.

  9. Modulation of Strawberry/Cranberry Phenolic Compounds Glucuronidation by Co-Supplementation with Onion: Characterization of Phenolic Metabolites in Rat Plasma Using an Optimized μSPE-UHPLC-MS/MS Method.

    Science.gov (United States)

    Dudonné, Stéphanie; Dubé, Pascal; Pilon, Geneviève; Marette, André; Jacques, Hélène; Weisnagel, John; Desjardins, Yves

    2014-04-09

    Plant phenolic compounds are suggested to exert pharmacological activities in regards to obesity and type-2 diabetes, but their mode of action is poorly understood due to a lack of information about their bioavailability. This work aimed to study the bioavailability of GlucoPhenol phenolic compounds, a strawberry-cranberry extracts blend, by characterizing plasma phenolic profile in obese rats. A comparison was performed by co-supplementation with an onion extract. Using an optimized μSPE-UHPLC-MS/MS method, 21 phenolic metabolites were characterized, mostly conjugated metabolites and microbial degradation products of the native phenolic compounds. Their kinetic profiles revealed either an intestinal or hepatic formation. Among identified metabolites, isorhamnetin glucuronide sulfate was found in greater amount in plasma. Three glucuronidated conjugates of strawberry-cranberry phenolic compounds, p-hydroxybenzoic acid glucuronide, catechins glucuronide, and methyl catechins glucuronide were found in higher quantities when GlucoPhenol was ingested together with onion extract (+252%, +279%, and +118% respectively), suggesting a possible induction of glucuronidation processes by quercetin. This work allowed the characterization of actual phenolic metabolites generated in vivo following a phenolic intake, the analysis of their kinetics and suggested a possible synergistic activity of phenolic compounds for improving bioavailability.

  10. Inhibition of glucuronidation and oxidative metabolism of buprenorphine using GRAS compounds or dietary constituents/supplements: in vitro proof of concept.

    Science.gov (United States)

    Maharao, Neha V; Joshi, Anand A; Gerk, Phillip M

    2017-03-01

    The present study investigated the potential of generally recognized as safe (GRAS) compounds or dietary substances to inhibit the presystemic metabolism of buprenorphine and to increase its oral bioavailability. Using IVIVE, buprenorphine extraction ratios in intestine and liver were predicted as 96% and 71%, respectively. In addition, the relative fraction of buprenorphine metabolized by oxidation and glucuronidation in these two organs was estimated using pooled human intestinal and liver microsomes. In both organs, oxidation appeared to be the major metabolic pathway with a 6 and 4 fold higher intrinsic clearance than glucuronidation in intestine and liver, respectively. The oral bioavailability of buprenorphine was predicted to be 1.16%. Inhibition of 75% and 50% of intestinal and hepatic presystemic metabolism would result in an F oral of 49%, which is comparable to the bioavailability of sublingual buprenorphine. In human liver microsomes, chrysin, curcumin, ginger extract, hesperitin, magnolol, quercetin and silybin inhibited ≥50% glucuronidation, whereas chrysin, curcumin, ginger extract, 6-gingerol, pterostilbene, resveratrol and silybin exhibited ≥30% inhibition of oxidation. In human intestinal microsomes, curcumin, ginger extract, α-mangostin, quercetin and silybin inhibited ≥50% glucuronidation while chrysin, ginger extract, α-mangostin, pterostilbene and resveratrol exhibited ≥30% inhibition of oxidation. These results demonstrate the feasibility of our proposed approach of using GRAS or dietary compounds to inhibit the presystemic metabolism of buprenorphine and thus improve its oral bioavailability. An oral buprenorphine formulation containing these inhibitors or their combinations has promising potential to replace sublingual buprenorphine. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Quantification of cannabinoids and their free and glucuronide metabolites in whole blood by disposable pipette extraction and liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Scheidweiler, Karl B; Newmeyer, Matthew N; Barnes, Allan J; Huestis, Marilyn A

    2016-07-01

    Identifying recent cannabis intake is confounded by prolonged cannabinoid excretion in chronic frequent cannabis users. We previously observed detection times ≤2.1h for cannabidiol (CBD) and cannabinol (CBN) and Δ(9)-tetrahydrocannabinol (THC)-glucuronide in whole blood after smoking, suggesting their applicability for identifying recent intake. However, whole blood collection may not occur for up to 4h during driving under the influence of drugs investigations, making a recent-use marker with a 6-8h detection window helpful for improving whole blood cannabinoid interpretation. Other minor cannabinoids cannabigerol (CBG), Δ9-tetrahydrocannabivarin (THCV), and its metabolite 11-nor-9-carboxy-THCV (THCVCOOH) might also be useful. We developed and validated a sensitive and specific liquid chromatography-tandem mass spectrometry method for quantification of THC, its phase I and glucuronide phase II metabolites, and 5 five minor cannabinoids. Cannabinoids were extracted from 200μL whole blood via disposable pipette extraction, separated on a C18 column, and detected via electrospray ionization in negative mode with scheduled multiple reaction mass spectrometric monitoring. Linear ranges were 0.5-100μg/L for THC and 11-nor-9-carboxy-THC (THCCOOH); 0.5-50μg/L for 11-hydroxy-THC (11-OH-THC), CBD, CBN, and THC-glucuronide; 1-50μg/L for CBG, THCV, and THCVCOOH; and 5-500μg/L for THCCOOH-glucuronide. Inter-day accuracy and precision at low, mid and high quality control (QC) concentrations were 95.1-113% and 2.4-8.5%, respectively (n=25). Extraction recoveries and matrix effects at low and high QC concentrations were 54.0-84.4% and -25.8-30.6%, respectively. By simultaneously monitoring multiple cannabinoids and metabolites, identification of recent cannabis administration or discrimination between licit medicinal and illicit recreational cannabis use can be improved. Published by Elsevier B.V.

  12. Pregnane × Receptor (PXR expression in colorectal cancer cells restricts irinotecan chemosensitivity through enhanced SN-38 glucuronidation

    Directory of Open Access Journals (Sweden)

    Lumbroso Serge

    2010-03-01

    Full Text Available Abstract Background Clinical efficacy of chemotherapy in colorectal cancer is subjected to broad inter-individual variations leading to the inability to predict outcome and toxicity. The topoisomerase I inhibitor irinotecan (CPT-11 is worldwide approved for the treatment of metastatic colorectal cancer and undergoes extensive peripheral and tumoral metabolism. PXR is a xenoreceptor activated by many drugs and environmental compounds regulating the expression of drug metabolism and transport genes in detoxification organs such as liver and gastrointestinal tract. Considering the metabolic pathway of irinotecan and the tissue distribution of Pregnane × Receptor (PXR, we hypothesized that PXR could play a key role in colon cancer cell response to irinotecan. Results PXR mRNA expression was quantified by RT-quantitative PCR in a panel of 14 colon tumor samples and their matched normal tissues. PXR expression was modulated in human colorectal cancer cells LS174T, SW480 and SW620 by transfection and siRNA strategies. Cellular response to irinotecan and its active metabolic SN38 was assessed by cell viability assays, HPLC metabolic profiles and mRNA quantification of PXR target genes. We showed that PXR was strongly expressed in colon tumor samples and displayed a great variability of expression. Expression of hPXR in human colorectal cancer cells led to a marked chemoresistance to the active metabolite SN38 correlated with PXR expression level. Metabolic profiles of SN38 showed a strong enhancement of SN38 glucuronidation to the inactive SN38G metabolite in PXR-expressing cells, correlated with an increase of UDPglucuronosyl transferases UGT1A1, UGT1A9 and UGT1A10 mRNAs. Inhibition of PXR expression by lentivirus-mediated shRNA, led to SN38 chemoresistance reversion concomitantly to a decrease of UGT1A1 expression and SN38 glucuronidation. Similarly, PXR mRNA expression levels correlated to UGT1A subfamily expression in human colon tumor biopsies

  13. Free and Glucuronide Whole Blood Cannabinoids' Pharmacokinetics after Controlled Smoked, Vaporized, and Oral Cannabis Administration in Frequent and Occasional Cannabis Users: Identification of Recent Cannabis Intake.

    Science.gov (United States)

    Newmeyer, Matthew N; Swortwood, Madeleine J; Barnes, Allan J; Abulseoud, Osama A; Scheidweiler, Karl B; Huestis, Marilyn A

    2016-12-01

    There is increasing interest in markers of recent cannabis use because following frequent cannabis intake, Δ 9 -tetrahydrocannabinol (THC) may be detected in blood for up to 30 days. The minor cannabinoids cannabidiol, cannabinol (CBN), and THC-glucuronide were previously detected for ≤2.1 h in frequent and occasional smokers' blood after cannabis smoking. Cannabigerol (CBG), Δ 9 -tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-THCV might also be recent use markers, but their blood pharmacokinetics have not been investigated. Additionally, while smoking is the most common administration route, vaporization and edibles are frequently used. We characterized blood pharmacokinetics of THC, its phase I and phase II glucuronide metabolites, and minor cannabinoids in occasional and frequent cannabis smokers for 54 (occasional) and 72 (frequent) hours after controlled smoked, vaporized, and oral cannabis administration. Few differences were observed between smoked and vaporized blood cannabinoid pharmacokinetics, while significantly greater 11-nor-9-carboxy-THC (THCCOOH) and THCCOOH-glucuronide concentrations occurred following oral cannabis. CBG and CBN were frequently identified after inhalation routes with short detection windows, but not detected following oral dosing. Implementation of a combined THC ≥5 μg/L plus THCCOOH/11-hydroxy-THC ratio tests. Clinicaltrials.gov Identifier: NCT02177513. © 2016 American Association for Clinical Chemistry.

  14. Isolation and characterization of a β-glucuronide of hydroxylated SARM S1 produced using a combination of biotransformation and chemical oxidation.

    Science.gov (United States)

    Rydevik, Axel; Lagojda, Andreas; Thevis, Mario; Bondesson, Ulf; Hedeland, Mikael

    2014-09-01

    In this study, using mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy, it has been confirmed that biotransformation with the fungus Cunninghamella elegans combined with chemical oxidation with the free radical tetramethylpiperidinyl-1-oxy (TEMPO) can produce drug glucuronides of β-configuration. Glucuronic acid conjugates are a common type of metabolites formed by the human body. The detection of such conjugates in doping control and other kinds of forensic analysis would be beneficial owing to a decrease in analysis time as hydrolysis can be omitted. However the commercial availability of reference standards for drug glucuronides is poor. The selective androgen receptor modulator (SARM) SARM S1 was incubated with the fungus C. elegans. The sample was treated with the free radical TEMPO oxidizing agent and was thereafter purified by SPE. A glucuronic acid conjugate was isolated using a fraction collector connected to an ultra high performance liquid chromatographic (UHPLC) system. The isolated compound was characterized by NMR spectroscopy and mass spectrometry and its structure was confirmed as a glucuronic acid β-conjugate of hydroxylated SARM S1 bearing the glucuronide moiety on carbon C-10. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Analysis of methylphosphonic acid, ethyl methylphosphonic acid and isopropyl methylphosphonic acid at low microgram per liter levels in groundwater.

    Science.gov (United States)

    Sega, G A; Tomkins, B A; Griest, W H

    1997-11-28

    A method is described for determining methylphosphonic acid, ethyl methylphosphonic acid and isopropyl methylphosphonic acid, which are hydrolysis products of the nerve agents VX (S-2-diisopropylaminoethyl O-ethyl methylphosphonothiolate) and GB (sarin, isopropylmethyl phosphonofluoridate). The analytes are extracted from 50 ml groundwater using a solid-phase extraction column packed with 500 mg of silica with a bonded quaternary amine phase, and are eluted and derivatized with methanolic trimethylphenylammonium hydroxide. Separation and quantitation are achieved using a capillary column gas chromatograph equipped with a flame photometric detector operated in its phosphorus-selective mode. Two independent statistically-unbiased procedures were employed to determine the detection limits, which ranged between 3 and 9 micrograms/l, for the three analytes.

  16. Urinary steroid hormone analysis of ovarian cycles and pregnancy in mandrills (Mandrillus sphinx) indicate that menses, copulatory behavior, sexual swellings and reproductive condition are associated with changing estrone conjugates (E(1)C) and pregnanediol-3-glucuronide (PdG).

    Science.gov (United States)

    Phillips, Rebecca Sellin; Wheaton, Catharine J

    2008-07-01

    The objective of this study was to determine if sexual swellings in mandrills (Mandrillus sphinx) are a reflection of reproductive endocrine state. Urine samples were assayed using an enzyme immunoassay measuring pregnanediol-3-glucuronide (PdG) and estrone conjugates (E(1)C). Hormone patterns of ovarian cycles, pregnancy and lactation were characterized and compared with sexual swellings and copulations relative to menses and peak E(1)C. Cycle lengths averaging 28.7 days and pregnancy length of 181 days determined by hormonal and sexual swelling measures were similar to those reported in other Old World primate species. First day of copulation was observed during rising E(1)C concentrations and preceded observations of peak swelling by 1-2 days. Observations of peak sexual swellings occurred at or on the day after peak E(1)C and decreased following the ovulatory increase in PdG. Observations of menses and sexual swellings are a useful method to track mandrill ovarian cycles and can assist zoos in determining the reproductive state of females in their collections. Zoo Biol 27:320-330, 2008. (c) 2008 Wiley-Liss, Inc.

  17. Bidirectional placental transfer of Bisphenol A and its main metabolite, Bisphenol A-Glucuronide, in the isolated perfused human placenta.

    Science.gov (United States)

    Corbel, T; Gayrard, V; Puel, S; Lacroix, M Z; Berrebi, A; Gil, S; Viguié, C; Toutain, P-L; Picard-Hagen, N

    2014-08-01

    The widespread human exposure to Bisphenol A (BPA), an endocrine disruptor interfering with developmental processes, raises the question of the risk for human health of BPA fetal exposure. In humans, highly variable BPA concentrations have been reported in the feto-placental compartment. However the human fetal exposure to BPA still remains unclear. The aim of the study was to characterize placental exchanges of BPA and its main metabolite, Bisphenol A-Glucuronide (BPA-G) using the non-recirculating dual human placental perfusion. This high placental bidirectional permeability to the lipid soluble BPA strongly suggests a transport by passive diffusion in both materno-to-fetal and feto-to-maternal direction, leading to a calculated ratio between fetal and maternal free BPA concentrations of about 1. In contrast, BPA-G has limited placental permeability, particularly in the materno-to-fetal direction. Thus the fetal exposure to BPA conjugates could be explained mainly by its limited capacity to extrude BPA-G. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. The effect of varying the peptide linker length in a single chain variable fragment antibody against wogonin glucuronide.

    Science.gov (United States)

    Paudel, Madan Kumar; Sakamoto, Seiichi; Van Huy, Le; Tanaka, Hiroyuki; Miyamoto, Tomofumi; Morimoto, Satoshi

    2017-06-10

    Peptide linkers of three different lengths were constructed to join the variable regions of the heavy chain (VH) and the light chain (VL) in a single-chain variable fragment antibody (scFv) specific for wogonin glucuronide (Wgn) that has the structure VH-(GGGGS) n -VL (n=3, 5, or 7). The scFv antibodies, which were expressed in Escherichia coli, were derived from an anti-Wgn monoclonal antibody (315A). An indirect competitive enzyme-linked immunosorbent assay (icELISA) was used to evaluate their reactivity and sensitivity, which is also used for quantitative analysis of Wgn. Our results, showed that the reactivity and specificity of the three different scFvs were, in fact, similar. Subsequently, the scFv having a VH-(GGGGS) 3 -VL linker which was slightly better that other two scFvs against Wgn, was applied to indirect competitive ELISA (icELISA) to analyze Scutellariae Radix (S. Radix). The utility of the icELISA was demonstrated for quality control and analysis of S. Radix in this report. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. [HPLC fingerprint of ethyl acetate extraction of Saxifraga stolonifera].

    Science.gov (United States)

    Zhou, Mei; Chen, Hua-Guo; Xian, Chun; Huang, Zhi-Jin; Zhou, Xin

    2013-04-01

    To establish an HPLC fingerprint of ethyl acetate extraction of Saxifraga stolonifera. The HPLC analysis was performed on a Diamonsil C18 (4.6 mm x 250 mm, 5 microm) column with isocratic elution of acetonitrile-0.05% phosphoric acid at a flow rate of 1.0 mL x min(-1). The detection wavelength was set at 256 nm and the column temperature was set at 30 degrees C. The HPLC fingerprint of ethyl acetate extraction of S. stolonifera has been established. There were fifteen common peaks, seven of which were identified by reference substances. The RSD of relative retention time was less than 3% in the precision and repeated tests. Eleven samples from different area can be distinguished from their fingerprints. This method is reasonable and reliable and can be used for quality control of S. stolonifera.

  20. SPECTROSCOPIC CHARACTERIZATION AND DETECTION OF ETHYL MERCAPTAN IN ORION

    Energy Technology Data Exchange (ETDEWEB)

    Kolesniková, L.; Alonso, J. L.; Daly, A. M. [Grupo de Espectroscopía Molecular (GEM), Edificio Quifima, Laboratorios de Espectroscopía y Bioespectroscopía, Parque Científico UVa, Unidad Asociada CSIC, Universidad de Valladolid, E-47011 Valladolid (Spain); Tercero, B.; Cernicharo, J. [Departamento de Astrofísica, Centro de Astrobiología CAB, CSIC-INTA, Ctra. de Torrejón a Ajalvir km 4, E-28850 Madrid (Spain); Gordon, B. P.; Shipman, S. T., E-mail: lucie.kolesnikova@uva.es, E-mail: jlalonso@qf.uva.es, E-mail: adammichael.daly@uva.es, E-mail: terceromb@cab.inta-csic.es, E-mail: jcernicharo@cab.inta-csic.es, E-mail: brittany.gordon@ncf.edu, E-mail: shipman@ncf.edu [Division of Natural Sciences, New College of Florida, Sarasota, FL 34243 (United States)

    2014-03-20

    New laboratory data of ethyl mercaptan, CH{sub 3}CH{sub 2}SH, in the millimeter- and submillimeter-wave domains (up to 880 GHz) provided very precise values of the spectroscopic constants that allowed the detection of gauche-CH{sub 3}CH{sub 2}SH toward Orion KL. This identification is supported by 77 unblended or slightly blended lines plus no missing transitions in the range 80-280 GHz. A detection of methyl mercaptan, CH{sub 3}SH, in the spectral survey of Orion KL is reported as well. Our column density results indicate that methyl mercaptan is ≅ 5 times more abundant than ethyl mercaptan in the hot core of Orion KL.

  1. Bioequivalence Demonstration for Ω-3 Acid Ethyl Ester Formulations: Rationale for Modification of Current Guidance.

    Science.gov (United States)

    Maki, Kevin C; Johns, Colleen; Harris, William S; Puder, Mark; Freedman, Steven D; Thorsteinsson, Thorsteinn; Daak, Ahmed; Rabinowicz, Adrian L; Sancilio, Frederick D

    2017-03-01

    The US Food and Drug Administration (FDA) draft guidance for establishing bioequivalence (BE) of ω-3 acid ethyl esters (containing both eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA] as ethyl esters), used to treat severe hypertriglyceridemia, recommends the conduct of 2 studies: one with participants in the fasting state and one with participants in the fed state. For the fasting study, the primary measures of BE are baseline-adjusted EPA and DHA levels in total plasma lipids. For the fed study, the primary measures of BE are EPA and DHA ethyl esters in plasma. This guidance differs from that established for icosapent ethyl (EPA ethyl esters) in which the primary measure of BE is baseline-adjusted total EPA in plasma lipids for both the fasting and fed states. The FDA guidance for ω-3 acid ethyl esters is not supported by their physiologic characteristics and triglyceride-lowering mechanisms because EPA and DHA ethyl esters are best characterized as pro-drugs. This article presents an argument for amending the FDA draft guidance for ω-3 acid ethyl esters to use baseline-adjusted EPA and DHA in total plasma lipids as the primary measures of BE for both fasting and fed conditions. This change would harmonize the approaches for demonstration of BE for ω-3 acid ethyl esters and icosapent ethyl (EPA ethyl esters) products for future development programs and is the most physiologically rational approach to BE testing. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  2. Physiologically based pharmacokinetic modeling of ethyl acetate and ethanol in rodents and humans.

    Science.gov (United States)

    Crowell, S R; Smith, J N; Creim, J A; Faber, W; Teeguarden, J G

    2015-10-01

    A physiologically based pharmacokinetic (PBPK) model was developed and applied to a metabolic series approach for the ethyl series (i.e., ethyl acetate, ethanol, acetaldehyde, and acetate). This approach bases toxicity information on dosimetry analyses for metabolically linked compounds using pharmacokinetic data for each compound and toxicity data for parent or individual compounds. In vivo pharmacokinetic studies of ethyl acetate and ethanol were conducted in rats following IV and inhalation exposure. Regardless of route, ethyl acetate was rapidly converted to ethanol. Blood concentrations of ethyl acetate and ethanol following both IV bolus and infusion suggested linear kinetics across blood concentrations from 0.1 to 10 mM ethyl acetate and 0.01-0.8 mM ethanol. Metabolic parameters were optimized and evaluated based on available pharmacokinetic data. The respiratory bioavailability of ethyl acetate and ethanol were estimated from closed chamber inhalation studies and measured ventilation rates. The resulting ethyl series model successfully reproduces blood ethyl acetate and ethanol kinetics following IV administration and inhalation exposure in rats, and blood ethanol kinetics following inhalation exposure to ethanol in humans. The extrapolated human model was used to derive human equivalent concentrations for the occupational setting of 257-2120 ppm ethyl acetate and 72-517 ppm ethyl acetate for continuous exposure, corresponding to rat LOAELs of 350 and 1500 ppm. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Impact of Association Colloids on Lipid Oxidation in Triacylglycerols and Fatty Acid Ethyl Esters.

    Science.gov (United States)

    Homma, Rika; Suzuki, Karin; Cui, Leqi; McClements, David Julian; Decker, Eric A

    2015-11-25

    The impact of association colloids on lipid oxidation in triacylglycerols and fatty acid ethyl esters was investigated. Association colloids did not affect lipid oxidation of high oleic safflower and high linoleic safflower triacylglycerols, but were prooxidative in fish triacylglycerols. Association colloids retarded aldehyde formation in stripped ethyl oleate, linoleate, and fish oil ethyl esters. Interfacial tension revealed that lipid hydroperoxides were surface active in the presence of the surfactants found in association colloids. The lipid hydroperoxides from ethyl esters were less surface active than triacylglycerol hydroperoxides. Stripping decreased iron and copper concentrations in all oils, but more so in fatty acid ethyl esters. The combination of lower hydroperoxide surface activity and low metal concentrations could explain why association colloids inhibited lipid oxidation in fatty acid ethyl esters. This research suggests that association colloids could be used as an antioxidant technology in fatty acid ethyl esters.

  4. Physical Properties of Ethyl Methacrylate as a Bolus in Radiotherapy

    Directory of Open Access Journals (Sweden)

    Atousa Montaseri

    2012-03-01

    Full Text Available Introduction Bolus is a soft and resilient material which is used for increasing skin dose or to even out the irregular patient contour. The main property of various materials used presently as bolus is the water-equivalent electron density. Ethyl methacrylate is used as a soft-liner in dentistry and its physical and chemical properties are proved to be nontoxic for human body. The goal of this study was to assess the feasibility of using this material as bolus in radiotherapy and also evaluating some parameters such as mass, electron densities, and transmission factors. Materials and Methods Computed tomography data from the sample material were acquired to assess mass and electron densities with various techniques (mA and kVp. Circular ROIs were delineated on CT DICOM images and densities were calculated using CT numbers. Transmission factors were calculated for 6 and 18 MV. Results Evaluation of our results are evident that showed that mass and electron densities of ethyl methacrylate are similar to those of water and soft tissue. Furthermore, transmission factors are close to those of water. Conclusion According to the results of this study and other properties such as flexibility and harmlessness, it seems that ethyl methacrylate is a suitable material to be used as bolus in radiotherapy.

  5. Sensory reception of the primer pheromone ethyl oleate

    Science.gov (United States)

    Muenz, Thomas S.; Maisonnasse, Alban; Plettner, Erika; Le Conte, Yves; Rössler, Wolfgang

    2012-05-01

    Social work force distribution in honeybee colonies critically depends on subtle adjustments of an age-related polyethism. Pheromones play a crucial role in adjusting physiological and behavioral maturation of nurse bees to foragers. In addition to primer effects of brood pheromone and queen mandibular pheromone—both were shown to influence onset of foraging—direct worker-worker interactions influence adult behavioral maturation. These interactions were narrowed down to the primer pheromone ethyl oleate, which is present at high concentrations in foragers, almost absent in young bees and was shown to delay the onset of foraging. Based on chemical analyses, physiological recordings from the antenna (electroantennograms) and the antennal lobe (calcium imaging), and behavioral assays (associative conditioning of the proboscis extension response), we present evidence that ethyl oleate is most abundant on the cuticle, received by olfactory receptors on the antenna, processed in glomeruli of the antennal lobe, and learned in olfactory centers of the brain. The results are highly suggestive that the primer pheromone ethyl oleate is transmitted and perceived between individuals via olfaction at close range.

  6. Evaluation and Characterization of Biodiesels Obtained Through Ethylic or Methylic Transesterification of Tryacylglicerides in Corn Oil

    Directory of Open Access Journals (Sweden)

    Douglas Queiroz Santos

    2014-06-01

    Full Text Available This work was devoted to the transesterification of corn oil either with methyl or ethyl alcohol and to the characterization of the biodiesels (composed by FAME—fatty acid methyl esters—or FAEE—fatty acid ethyl esters, respectively produced. As an initial hypothesis, it was argued whether or not the two alcohols, both with short molecular chains, would impart significant differences to the chemical characteristics of the two biodiesels from corn oil. The most common properties of the biodiesels were evaluated by determining corresponding parameters for acid value, peroxide value, water content, oxidative stability, free and total glycerin, kinematic viscosity at 40 ℃ and density at 20 ℃, for both chemical routes, FAME and FAEE. In general, values were found to be well within the recommended limits for commercial biodiesel, in accordance with the Brazilian, European and American standard recommendations, except only for the oxidative stability. The methyl biodiesel presented acidity of 0.08 mg KOH/g; peroxide index, 23.77 meq/kg; oxidation stability, 3.10 h; water content, 297.1 mg/kg; total glycerin, 0.092 %; free glycerin, 0.009 %; viscosity, 4.05 mm2/s and density, 878.7 kg/m. The methyl biodiesel presented acidity of 0.11 mg/ KOH; peroxide index, 22.39 meq/kg; oxidation stability, 2.13 h; water content, 264.8 mg/kg; total glycerin, 0.25 %; free glycerin, 0.02 %; viscosity, 4.37 mm2/s and density, 874.0 kg/m. From a direct inspection of chemical data for the two products prepared via the two chemical routes, it can be drawn that values of the physical and chemical parameters for both, methyl and ethyl biodiesels, are essentially similar, except for the oxidative stability. However, the oxidative stability can be suitably adjusted by adding an anti-oxidizing agent to the ethyl biodiesel medium. The two biodiesels are thus promising alternatives to fully replace or to be admixed to the mineral diesel. Relatively to the pure petrol

  7. Antimicrobial activity of Butyl acetate, Ethyl acetate and Isopropyl alcohol on undesirable microorganisms in cosmetic products.

    Science.gov (United States)

    Lens, C; Malet, G; Cupferman, S

    2016-10-01

    The microbiological contamination risk of a cosmetic product has to be assessed by the manufacturer, according to the composition, to determine whether microbiological testing is required. Certain ingredients in cosmetic formulations help to create an environment hostile towards microbial growth. In this study, the influence on microbial survival of some solvents used in nail varnishes was evaluated. The purpose of this study was two-fold. The first was to define the thresholds to be considered for the exemption of products from microbiological testing. The second was to assess the cross-contamination risk linked to the use on successive consumers of solvent-based products in beauty salons. Strains of Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Candida albicans and Trichophyton rubrum were exposed to various concentrations of ethyl acetate, butyl acetate and isopropyl alcohol in culture medium to estimate their MIC (minimum inhibitory concentration). These strains are relevant to cosmetic products as they are associated with skin and nail infections. Mixtures of the three solvents, which are characteristic of nail varnish compositions, were also tested for their cidal activity. Ethyl and butyl acetates had a stronger impact than isopropyl alcohol: the MIC of ethyl and butyl acetate is ≤5% for all of the tested strains, whereas that of isopropyl alcohol is ≤10%. Various combinations of the three solvents tested showed a significant effect on both fungal and bacterial strains (greater than 3 log reduction in 15 min for the bacterial test strains and in 30 min for T. rubrum). Products containing more than 5% ethyl or butyl acetate or more than 10% isopropyl alcohol are hostile towards microbial growth. These products can therefore be considered as microbiologically low risk during both production and use, and so do not require microbiological testing (challenge test and end-product testing). Moreover, the nine tested mixtures of these three

  8. Spectroscopic study and astronomical detection of doubly 13C-substituted ethyl cyanide

    Science.gov (United States)

    Margulès, L.; Belloche, A.; Müller, H. S. P.; Motiyenko, R. A.; Guillemin, J.-C.; Garrod, R. T.; Menten, K. M.

    2016-05-01

    Context. We have performed a spectral line survey called Exploring Molecular Complexity with ALMA (EMoCA) toward Sagittarius B2(N) between 84.1 and 114.4 GHz with the Atacama Large Millimeter/submillimeter Array (ALMA) in its Cycles 0 and 1. Line intensities of the main isotopic species of ethyl cyanide and its singly 13C-substituted isotopomers observed toward the hot molecular core Sagittarius B2(N2) suggest that the doubly 13C-substituted isotopomers should also be detectable. Aims: We want to determine the spectroscopic parameters of all three doubly 13C-substituted isotopologues of ethyl cyanide to search for them in our ALMA data. Methods: We investigated the laboratory rotational spectra of the three species between 150 GHz and 990 GHz. We searched for emission lines produced by these species in the ALMA spectrum of Sagittarius B2(N2). We modeled their emission and the emission of the 12C and singly 13C-substituted isotopologues assuming local thermodynamic equilibrium. Results: We identified more than 5000 rotational transitions, pertaining to more than 3500 different transition frequencies, in the laboratory for each of the three doubly 13C-substituted isotopomers. The quantum numbers reach J ≈ 115 and Ka ≈ 35, resulting in accurate spectroscopic parameters and accurate rest frequency calculations beyond 1000 GHz for strong to moderately weak transitions of either isotopomer. All three species are unambiguously detected in our ALMA data. The 12C/13C column density ratio of the isotopomers with one 13C atom to those with two 13C atoms is about 25. Conclusions: Ethyl cyanide is the second molecule after methyl cyanide for which isotopologues containing two 13C atoms have been securely detected in the interstellar medium. The model of our ethyl cyanide data suggests that we should be able to detect vibrational satellites of the main species up to at least ν19 = 1 at ~1130 K and up to ν13 + ν21 = 2 at ~600 K for the isotopologues with one 13C atom in

  9. C-24 stereochemistry of marine Sterols: (22E)-24-Ethyl-24-methylcholesta-5,22-dien-3{beta}-ol and 24-Ethyl-24-methylcholest-5-en-3{beta}-ol

    Energy Technology Data Exchange (ETDEWEB)

    Echigo, Shizue; Uekusa, Hidehiro; Hara, Noriyuki; Fujimoto, Yoshinori [Tokyo Institute of Technology, Meguro, Tokyo (Japan). Dept. of Chemistry and Materials Science; Castellanos, Leonardo; Duque, Carmenza, E-mail: cduqueb@unal.edu.c [Universidad Nacional de Colombia, Bogota (Colombia). Dept. de Quimica

    2011-07-01

    The C-24 configurations of (22E)-24-ethyl-24-methylcholesta-5,22-dien-3{beta}-ol (1) and 24-ethyl- 24-methylcholest-5-en-3{beta}-ol (2), isolated from the Colombian Caribbean sponge Topsentia ophiraphidites, were determined to be R and S, respectively, by comparing their NMR data with those of stereodefined (24R)- and (24S)-samples that were synthesized in routes involving the orthoester Claisen rearrangement of {Delta}{sup 23}-22-allylic alcohols. This is the first synthetic study where the Claisen rearrangement is used to introduce a C-24 quaternary center in a stereospecific manner with acceptable yield. X-ray analysis of 1 confirmed these stereochemical assignments. (author)

  10. Vapor-liquid equilibrium for the system ethyl alcohol + ester; Equilibrio liquido-vapor para o sistema alcool etilico+ester

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Humberto Neves Maia de; Nascimento, Yuri Corsino do; Chiavone-Filho, Osvaldo [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil)

    2004-07-01

    This work consists of the experimental determination of a series of vapor-liquid equilibrium (VLE) data, for mixtures of ethyl alcohol + ester (ethyl acetate), prepared synthetically, that may be present in the production of biodiesel. The separation of the ethyl alcohol from esters by distillation is an important stage of this process, and therefore it demands accurate data for an appropriate modelling, and later optimization via simulators. FISCHER'S ebulliometer, with digital control (Model 602), was used for measurement of VLE data for the system ethyl alcohol + ester. It consists of a recirculation cell of the both vapor and liquid phases, providing complete data, i.e., pressure, temperature and compositions of the liquid and vapor phases that were obtained by gaseous chromatography (PTxy). This apparatus is coupled to a thermostatic bath with cooling (TE-184 TECNAL) that aims to condense the coming steams of the ebullition in order to return to the mixture camera. The VLE data obtained experimentally were submitted to the test of thermodynamic consistence of the deviations, where the equation of Gibbs-Duhem is used, through the model UNIQUAC. The parameters obtained from the experimental data can be applied in the simulators of processes with the purpose of optimizing the separation of the ethyl alcohol of Ester. (author)

  11. Postharvest control of western flower thrips (Thysanoptera: Thripidae) and California red scale (Hemiptera: Diaspididae) with ethyl formate and its impact on citrus fruit quality.

    Science.gov (United States)

    Pupin, Francine; Bikoba, Veronique; Biasi, William B; Pedroso, Gabriel M; Ouyang, Yuling; Grafton-Cardwell, Elizabeth E; Mitcham, Elizabeth J

    2013-12-01

    The postharvest control of arthropod pests is a challenge that the California citrus industry must overcome when exporting fruit overseas. Currently, methyl bromide fumigation is used to control postharvest pests on exported citrus, but it may soon be unavailable because of use restrictions and cost of this health-hazard ozone-depleting chemical. Ethyl formate is a natural plant volatile and possible alternative to methyl bromide in postharvest insect control. The objectives of this study were 1) to evaluate the mortality of third instar California red scale [Aonidiella aurantii (Maskell)] (Hemiptera: Diaspididae) and adult western flower thrips [Frankliniella occidentalis (Pergande)] (Thysanoptera: Thripidae) under a wide range of ethyl formate concentrations, 2) to determine the ethyl formate concentration required to reach a Probit 9 level of control for both pests, and 3) to test the effects of ethyl formate fumigation on the quality of navel oranges [Citrus sinensis (L.) Osbeck] and lemons [Citrus limon (L.) Burman f.] at 24 h after fumigation, and at different time periods to simulate shipping plus storage (5 wk at 5 degrees C), and shipping, storage, handling, and shelf-life (5 wk at 5 degrees C, plus 5 d at 15 degrees C, and 2 d at 20 degrees C). The results indicate that ethyl formate is a promising alternative to methyl bromide for the California citrus industry, because of successful control of adult western flower thips and third instar California red scale and no deleterious effect on fruit quality at any of the evaluated periods and quality parameters.

  12. 3-Ethyl-2-(ethylimino-4-methyl-2,3-dihydro-1,3-thiazole-5-carboxylate Ethyl Ester

    Directory of Open Access Journals (Sweden)

    Ge Meng

    2016-11-01

    Full Text Available An efficient procedure to obtain the new compound 1a from ethyl acetoacetate (2a, NBS and N,N′-diethylthiourea (4a was reported. In comparison with the traditional method to synthesize its analogues, this efficient, catalyst-free, and one-pot synthetic method is facile. The work-up procedure is easy and gives the pure target compound under milder reaction conditions in a relatively high yield of 75%.

  13. p-Cresyl glucuronide is a major metabolite of p-cresol in mouse: in contrast to p-cresyl sulphate, p-cresyl glucuronide fails to promote insulin resistance.

    Science.gov (United States)

    Koppe, Laetitia; Alix, Pascaline M; Croze, Marine L; Chambert, Stéphane; Vanholder, Raymond; Glorieux, Griet; Fouque, Denis; Soulage, Christophe O

    2017-08-03

    The role of uraemic toxins in insulin resistance associated with chronic kidney disease (CKD) is gaining interest. p-Cresol has been defined as the intestinally generated precursor of the prototype protein-bound uraemic toxins p-cresyl sulphate (p-CS) as the main metabolite and, at a markedly lower concentration in humans, p-cresyl glucuronide (p-CG). The objective of the present study was to evaluate the metabolism of p-cresol in mice and to decipher the potential role of both conjugates of p-cresol on glucose metabolism. p-CS and p-CG were measured by high performance liquid chromatography-fluorescence in serum from control, 5/6 nephrectomized mice and mice injected intraperitoneously with either p-cresol or p-CG. The insulin sensitivity in vivo was estimated by insulin tolerance test. The insulin pathway in the presence of p-cresol, p-CG and/or p-CS was further evaluated in vitro on C2C12 muscle cells by measuring insulin-stimulated glucose uptake and the insulin signalling pathway (protein kinase B, PKB/Akt) by western blot. In contrast to in humans, where p-CS is the main metabolite of p-cresol, in CKD mice both conjugates accumulated, and after chronic p-cresol administration with equivalent concentrations but a substantial difference in protein binding (96% for p-CS and p-CG). p-CG exhibited no effect on insulin sensitivity in vivo or in vitro and no synergistic inhibiting effect in combination with p-CS. The relative proportion of the two p-cresol conjugates, i.e. p-CS and p-CG, is similar in mouse, in contrast to humans, pinpointing major inter-species differences in endogenous metabolism. Biologically, the sulpho- (i.e. p-CS) but not the glucuro- (i.e. p-CG) conjugate promotes insulin resistance in CKD.

  14. [The peculiar features of the distribution of 2-(dimethylamino)ethyl- (1-hydroxycyclopentyl) (phenyl) acetate in the organism of warm-blooded animals after its intravenous administration].

    Science.gov (United States)

    Shormanov, V K; Pravdyuk, M F

    The objective of the present study was to elucidate the dynamics of the distribution of 2-(dimethylamino)ethyl-(1-hydroxycyclopentyl)(phenyl) acetate in the organism of warm-blooded animals (rats) after its intravenous administration to the animals. The identification and the quantitative determination of 2-(dimethylamino)ethyl-(1-hydroxycyclopentyl)(phenyl) acetate present in the organs and blood of the warm-blooded animals were carried out with the use of chromatography in a thin layer of silica gel, chromogenic reaction for the synthesis of the acinitro salt, UV spectrophotometry, and gas chromatography mass-spectrometry (GCh-MS). The quantitation was performed on days 5, 20, 150, and 360 minutes after the intravenous administration of 2-(dimethylamino)ethyl-(1-hydroxycyclopentyl)(phenyl) acetate to the rats. The maximum amounts of cyclopentolate were found in the spleen, brain, lungs, and heart of the experimental animals.

  15. Development and validation of a radioreceptor assay for the determination of morphine and its active metabolites in serum

    NARCIS (Netherlands)

    de Jong, LAA; Kramer, K; Kroeze, MPH; Bischoff, R; Uges, DRA; Franke, JP

    2005-01-01

    This article describes the development and validation of a radioreceptor assay for the determination of morphine andmorphine-6-beta-glucuronide (M6G) in serum. The assay is based on competitive inhibition of the mu-opioid-selective radiolabeled ligand [H-3]-DAMGO by opioid ligands (e.g. M6G) for

  16. Mechanistic insights into the hydrolysis of 2-chloroethyl ethyl sulfide: the expanded roles of sulfonium salts.

    Science.gov (United States)

    Bae, Su Y; Winemiller, Mark D

    2013-07-05

    The hydrolysis of 2-chloroethyl ethyl sulfide has been examined in an effort to better understand its mechanism under more concentrated conditions. Two salts formed during hydrolysis were synthesized, and an emphasis was placed on determining their effect on the reaction as it proceeded. Unexpected changes in mechanism were seen when excess chloride was added to the reaction. By measuring rates and product distributions as the products were added back into the hydrolysis, a mechanism was developed. The formation of these sulfonium salts represents additional products in the disappearance of 2-chloroethyl ethyl sulfide with k3 in particular causing a deviation away from expected first-order behavior. Sulfonium salts 3 and 4 do not appear to interconvert, and the system as a whole had fewer pathways available than previously proposed. Initial conditions for studying the hydrolysis were very important and could lead to different conclusions depending on the conditions used. This work will aid in better understanding the hydrolysis of the very toxic chemical warfare agent mustard (bis(2-chloroethyl)sulfide) in the environment and during its decontamination.

  17. Acute toxicity profiling of the ethyl acetate fraction ofSwietenia macrophyllaseeds andin-vitroneuroprotection studies.

    Science.gov (United States)

    Sayyad, Mustak; Tiang, Ning; Kumari, Yatinesh; Goh, Bey Hing; Jaiswal, Yogini; Rosli, Rozita; Williams, Leonard; Shaikh, Mohd Farooq

    2017-02-01

    Swietenia macrophylla (SM) is a medicinally important plant found in tropical and subtropical regions of the world. The ethyl acetate fraction of the seeds of S. macrophylla (SMEAF) is reported to exhibit potent anticancer, antitumor, anti-inflammatory and antifeedant activities. Till date, there have been no studies reported on the acute oral toxicity profile of the ethyl acetate fraction of the seeds of SM. The objective of the present study was to determine the acute toxicity of SMEAF and evaluate the in - vitro neuroprotective activity of SMEAF using primary neuronal cell cultures. In acute oral toxicity study, the SMEAF did not produce any lethal signs of morbidity and mortality. Histo-pathological findings, support the safety of SMEAF, as there were no significant changes observed in any of the parameters studied. Based on the results obtained in MTT assay, we infer that SMEAF has a significant neuroprotective effect, as it increased the cell viability and exhibited protection to the neuronal cells against TBHP induced oxidative stress. Thus, SMEAF can be suggested for use in the development of herbal drug formulations with neuroprotective potential.

  18. Feoforbídeo (etoxi-purpurina-18 isolado de Gossypium mustelinum (Malvaceae Ethyl ester putpurin-18 from Gossypium mustelinum (Malvaceae

    Directory of Open Access Journals (Sweden)

    Tania Maria Sarmento Silva

    2010-01-01

    Full Text Available The phaeophorbide ethyl ester named Purpurin-18 and the flavonoids quercetin and kaempferol were obtained by chromatographic procedures from the chloroform fraction of aerial parts of Gossypium mustelinum. The structure of these compound was determined by NMR, IR and mass spectra data analysis. This is the first occurrence of this compound in Angiosperm.

  19. Simultaneous quantification of tizoxanide and tizoxanide glucuronide in mouse plasma by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Liu, Jinqiu; Meng, Fanhua; Li, Zhaofeng; Yu, Lin; Peng, Shuangqing; Guo, Jifen; Xu, Haiyan

    2016-11-01

    Nitazoxanide (NTZ) is a broad-spectrum antimicrobial agent. Tizoxanide (T) and tizoxanide glucuronide (TG) are the major circulating metabolites after oral administration of NTZ. A rapid and specific LC-MS/MS method for the simultaneous quantification of T and TG in mouse plasma was developed and validated. A simple acetonitrile-induced protein precipitation method was employed to extract two analytes and the internal standard glipizide from 50 μL of mouse plasma. The purified samples were resolved using a C18 column with a mobile phase consisting of acetonitrile and 5 mm ammonium formate buffer (containing 0.05% formic acid) following a gradient elution. An API 3000 triple quadrupole mass spectrometer was operated under multiple reaction-monitoring mode with electrospray ionization. The precursor-to-product ion transitions m/z 264 → m/z 217 for T and m/z 440 → m/z 264 for TG were used for quantification. The developed method was linear in the concentration ranges of 1.0-500.0 ng/mL for T and 5.0-1000.0 ng/mL for TG. The intra- and inter-day precision and accuracy of the quality control samples at low, medium and high concentrations exhibited an RSD of <13.2% and the accuracy values ranged from -9.6 to 9.3%. We used this validated method to study the pharmacokinetics of T and TG in mice following oral administration of NTZ. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  20. The TLR4-Active Morphine Metabolite Morphine-3-Glucuronide Does Not Elicit Macrophage Classical Activation In Vitro.

    Science.gov (United States)

    Khabbazi, Samira; Xie, Nan; Pu, Wenjun; Goumon, Yannick; Parat, Marie-Odile

    2016-01-01

    Macrophages are abundant in the tumor microenvironment where they adopt a pro-tumor phenotype following alternative polarization induced by paracrine factors from cancer and stromal cells. In contrast, classically activated macrophages have tumoricidal activities, such that the polarization of tumor-associated macrophages has become a novel therapeutic target. Toll-like receptor 4 engagement promotes classical activation of macrophages, and recent literature suggests TLR4 agonism to prevent metastasis and promote survival in experimental metastasis models. A growing number of studies indicate that TLR4 can respond to opioids, including the opioid receptor-inactive morphine metabolite morphine-3-glucuronide (M3G). We measured the activation of TLR4 in a reporter cell line exogenously expressing TLR4 and TLR4 co-receptors, and confirmed that M3G weakly but significantly activates TLR4. We hypothesized that M3G would promote the expression of classical activation signature genes in macrophages in vitro. We exposed mouse and human macrophage cell lines to M3G or the TLR4 activator lipopolysaccharide (LPS), alone or in combination with interferon gamma (IFN-γ). The classical macrophage activation markers tested were iNOS, CD86, IL-6, or TNF-α in RAW 264.7 cells and IL-6, IL-12, IL-23, TNF-α, CXCL10, and CXCL11 in THP1 cells. Our results show that despite exhibiting TLR4-activation ability, M3G does not elicit the expression of classical activation markers in LPS-responsive macrophages.

  1. The Influence of Active Transport Systems on Morphine -6-Glucuronide Transport in MDCKII and MDCK-PGP Cells

    Directory of Open Access Journals (Sweden)

    SO. Mashayekhi

    2011-12-01

    Full Text Available Background and the purpose of the study: Morphine-6-glucuronide (M6G is a potent metabolite of morphine which has high penetration into the brain despite its high polarity, which could be the result of an active transport system involved in M6G transport through blood brain barrier. Examples of such transporters are p-glycoprotein (PGP, probenecid-sensitive transport mechanism, multidrug resistance related protein 1-3, the organic anion transporter family, and the organic anion transporter polypeptide family. The aim of present study was to elucidate the mechanisms involved in transporting morphine's potent metabolite, M6G.Methods: M6G permeability via two cell lines; MDCKII and MDCK-PGP, was compared with that of sucrose. M6G transport was examined in different concentrations and in the presence of inhibitors of different transport systems such as cyclosporine, digoxin and probenecid. M6G concentration was measured using ELISA assay. The method was sensitive, reliable and reproducible.Results: The results confirmed that M6G could cross a layer of MDCK II or MDR-PGP cells more than sucrose could. It was also observed that M6G is a PGP transporter substrate. Its permeability was increased by the use of a PGP expressed cell line, and also in the presence of a strong PGP inhibitor. Digoxin related transporters such as Oatp2 may also involved in transport of M6G. M6G seemed to be a glucose transporter 1 substrate, but was not a substrate to probenecid sensitive transporters.Major conclusion: It is concluded that different transporters are responsible for M6G transports via different membrane, which could have effects on its pharmacokinetics or pharmacodynamics.

  2. Enzymatic synthesis of {sup 125/131}I labeled 8-hydroxyquinoline glucuronide and in vitro/in vivo evaluation of biological influence

    Energy Technology Data Exchange (ETDEWEB)

    Yesilagac, Reyhan [Ege University, Institute of Nuclear Science, 35100 Bornova, Izmir (Turkey); Unak, Perihan, E-mail: perihan.unak@ege.edu.t [Ege University, Institute of Nuclear Science, 35100 Bornova, Izmir (Turkey); Medine, E. Ilker; Ichedef, Cigdem A. [Ege University, Institute of Nuclear Science, 35100 Bornova, Izmir (Turkey); Ertay, Turkan [Dokuz Eyluel University, Medical School, Department of Nuclear Medicine, Inciralti, Izmir (Turkey); Mueftueler, F.Z. Biber [Ege University, Institute of Nuclear Science, 35100 Bornova, Izmir (Turkey)

    2011-02-15

    8-Hydroxyquinoline (8-OHQ) is a long-known molecule which due to its metal-complexation ability is frequently used for analysis. It is also called oxine. Oxine and derivatives have been investigated to process antitumor and antimicrobial activities. 8-Hydroxyquinolyl-glucuronide (8-OHQ-Glu) was enzymatically synthesized using microsome preparates separated from Hutu-80 cells, labeled with {sup 125}I to perform a radionuclide labeled prodrug and investigated of its biological affinities on Hutu-80 (human duodenum intestinal adenocarcinoma), Caco-2 (human colorectal adenocarcinoma), Detroit 562 (human pharynx adenocarcinoma) cells and ACBRI 519 (primary human small intestine epithelial cells) in this work. UDP-glucuronyl transferase (UDPGT) rich microsome preparates, which are used for glucuronidation in enzymatic synthesis, were extracted from Hutu-80 cells. 8-OHQ-Glu components were labeled using iodogen method with {sup 125}I and {sup 131}I. Structural analyses were performed with LC/MS/MS, {sup 1}H NMR and {sup 13}C-MMR for identify and measure chemical constituents. Results confirmed expected molecular structure. 8-OHQ-Glu could successfully radioiodinated with {sup 125/131}I according to iodogen method. {sup 125}I-8-OHQ-glucuronide incorporated with human gastrointestinal cancer cells such as Detroit-562 (human pharynx adenocarcinoma) (12.6%), Caco-2 (human colorectal adenocarcinoma) (7.8%), Hutu- 80 (human duodenum intestinal adenocarcinoma) (9.5%) and ACBRI 519 (primary human small intestine epithelial cells) (6.40%). {sup 131}I-8-OHQ-Glu was tested in mice bearing subcutaneously implanted Caco-2 colorectal adenocarcinoma cells. The results demonstrated that radioiodinated 8-OHQ-Glu may be promising anticancer prodrug.

  3. Development of a Liquid Chromatography Tandem Mass Spectrometric Method for Quantification of Mycophenolic Acid and Its Glucuronides in Dried Blood Spot Samples.

    Science.gov (United States)

    Iboshi, Hiromasa; Yamaguchi, Hiroaki; Suzuki, Hiroyuki; Kikuchi, Masafumi; Tanaka, Masaki; Takasaki, Shinya; Takahashi, Akiko; Maekawa, Masamitsu; Shimada, Miki; Matsuda, Yasushi; Okada, Yoshinori; Mano, Nariyasu

    2017-10-14

    Personalized immunosuppressive therapy, including accurate drug dosing based on drug blood level, leads to better clinical outcomes, specifically with regard to avoidance of drug-induced adverse effects and maintenance of efficacy. Mycophenolic acid (MPA) is used as an immunosuppressant in transplantation of various solid organs. The aim of this study was to develop a method for quantification of MPA and its metabolites, mycophenolic acid 7-O-glucuronide (MPAG) and mycophenolic acid acyl glucuronide, in dried blood spot (DBS) samples, using liquid chromatography/electrospray ionization/tandem mass spectrometry. For sample preparation, a microwave-drying approach was used to deactivate enzymes and reduce drying time. Blood volume was calculated in a DBS disk of 3 mm diameter. Concentrations of analytes in plasma from patients receiving mycophenolate mofetil were compared to DBS samples after hematocrit correction. The method yielded good recoveries of all three analytes (90.3-104.2%). Blood volume in the disk was calculated as 3.0 ± 0.2 µL. Linearity over concentration ranges of 0.1-30 µg/mL MPA, 0.1-200 µg/mL MPAG, and 0.125-10 µg/mL mycophenolic acid acyl glucuronide were obtained with r ≥ 0.999. Intra-day and inter-day variation were less than 14.6%, and accuracy was within ±11.9%. Passing-Bablok analysis showed no significant differences between plasma concentrations and DBS concentrations after hematocrit correction of MPA and MPAG. We developed and validated an LC/ESI-MS/MS method for analysis of MPA in DBS samples. The method is useful for monitoring MPA blood level.

  4. Lipopolysaccharide enhances the cytotoxicity of 2-chloroethyl ethyl sulfide

    OpenAIRE

    Stone, William L; Qui, Min; Smith, Milton

    2003-01-01

    Abstract Background The bacterial endotoxin, lipopolysaccharide (LPS), is a well-characterized inflammatory factor found in the cell wall of Gram-negative bacteria. In this investigation, we studied the cytotoxic interaction between 2-chloroethyl ethyl sulfide (CEES or ClCH2CH2SCH2CH3) and LPS using murine RAW264.7 macrophages. CEES is a sulfur vesicating agent and is an analog of 2,2'-dichlorodiethyl sulfide (sulfur mustard). LPS is a ubiquitous natural agent found in the environment. The ab...

  5. Ethyl 2-[3-(4-nitrobenzoylthioureido]benzoate

    Directory of Open Access Journals (Sweden)

    Sohail Saeed

    2010-04-01

    Full Text Available In the title compound, C17H15N3O5S, the nitro and thioureido groups are twisted by 7.2 (7 and 21.4 (2°, respectively, from the nitrobenzene ring plane whereas the thioureido and the ethyl ester group make dihedral angles of 43.0 (1 and 18.0 (2°, respectively, with the benzene rings to which they are attached. Intramolecular N—H...O hydrogen-bonding interactions are observed. In the crystal, intermolecular N—H...O hydrogen bonds connect the molecules into chains running along the a axis.

  6. Elevated ethyl methanesulfonate (EMS) in nelfinavir mesylate (Viracept?, Roche): overview

    OpenAIRE

    Jones Judith K; Salgo Miklos; Müller Lutz; Pozniak Anton; Larson Peter; Tweats David

    2009-01-01

    Abstract Roche's protease inhibitor nelfinavir mesylate (Viracept®) produced between March 2007-June 2007 was found to contain elevated levels of ethyl methanesulfonate (EMS), a known mutagen (alkylator) – leading to a global recall of the drug. EMS levels in a daily dose (2,500 mg Viracept/day) were predicted not to exceed a dose of ~2.75 mg/day (~0.055 mg/kg/day based on 50 kg patient). As existing toxicology data on EMS did not permit an adequate patient risk assessment, a comprehensive an...

  7. Direct Conversion of Carbohydrates into Ethyl Levulinate with Potassium Phosphotungstate as an Efficient Catalyst

    Directory of Open Access Journals (Sweden)

    Shiqiang Zhao

    2015-11-01

    Full Text Available A series of metal-modified phosphotungstates were prepared and performed for direct synthesis of ethyl levulinate from fructose in ethanol. Considering the cost of catalysts, catalytic activity of catalysts, and easy separation of catalysts together, K-HPW-1 was chosen as the most suitable catalyst for synthesis of ethyl levulinate from fructose. A high ethyl levulinate yield of 64.6 mol% was obtained at 150 °C within 2 h in ethanol. The introduction of low polar toluene as a co-solvent improved the yield of ethyl levulinate to 68.7 mol%. The recovered catalyst remained high activity with the yield of ethyl levulinate converted from fructose above 50 mol% after being used five times. Moreover, the generality of the catalyst was further demonstrated by glucose, sucrose, inulin, and cellulose with ethyl levulinate yielding 14.5, 35.4, 52.3, and 14.8 mol%, respectively.

  8. The effect of ethyl acetate fraction of Citrus limon peel on mesenchymal cell proliferation and polybacterial growth

    Directory of Open Access Journals (Sweden)

    Astrid Marinna

    2015-09-01

    Full Text Available Background: Oral diseases remain to be global health problem. The common therapy involved the use of modern medicines with their various side effects. Citrus limon are potentials as anti-inflammatory, anti-fungal, anti-oxidant, anti-viral and anti-bacterial. Purpose: The purpose of this study was to determine the effect of ethyl acetate fraction of citrus limon peel extract on human gingival mesenchymal cell proliferation and palm commensal polybacterial growth. Method: This study was experimental study with post test only control group design. Citrus limon peel extracted and partitioned in order to obtain ethyl acetate fraction of 3.125%, 2.75%, 2.375%, 2%, and 1.5625%. Toxicity test was performed after 24 hours using the MTT Assays. Cell viability was measured by optical density formazonand read by ELISA reader 620 nm. Results: All treatment groups showed less than 60% cell viability. The highest cell was 19.36 (1.5625% concentration and the lowest was 12.65 (3.125% concentration. The highest anti-bacterial inhibition value was 8.9125 mm (3.125% concentration and the lowest was 6.0625 mm (1.5625% concentration. Conclusion: The higher concentration of ethyl acetate fraction Citrus limon peel extract, the higher toxicity and inhibitory properties against commensal palm polybacteria.

  9. Assessment of Acute Oral and Dermal Toxicity of 2 Ethyl-Carbamates with Activity against Rhipicephalus microplus in Rats

    Directory of Open Access Journals (Sweden)

    María Guadalupe Prado-Ochoa

    2014-01-01

    Full Text Available The acute oral and dermal toxicity of two new ethyl-carbamates (ethyl-4-bromophenyl-carbamate and ethyl-4-chlorophenyl-carbamate with ixodicide activity was determined in rats. The oral LD50 of each carbamate was 300 to 2000 mg/kg, and the dermal LD50 of each carbamate was >5000 mg/kg. Clinically, the surviving rats that had received oral doses of each carbamate showed decreased weight gain (P<0.05 and had slight nervous system manifestations. These clinical signs were evident from the 300 mg/kg dose and were reversible, whereas the 2000 mg/kg dose caused severe damage and either caused their death or was motive for euthanasia. At necropsy, these rats had dilated stomachs and cecums with diffuse congestion, as well as moderate congestion of the liver. Histologically, the liver showed slight degenerative lesions, binucleated hepatocytes, focal coagulative necrosis, and congestion areas; the severity of the lesions increased with dosage. Furthermore, an slight increase in gamma-glutamyltransferase, lactate dehydrogenase, and creatinine was observed in the plasma. The dermal application of the maximum dose (5000 mg/kg of each carbamate did not cause clinical manifestations or liver and skin alterations. This finding demonstrates that the carbamates under study have a low oral hazard and low acute dermal toxicity.

  10. The millimeter and sub-millimeter rotational spectrum of triple 13C-substituted ethyl cyanide

    Science.gov (United States)

    Pienkina, A. O.; Margulès, L.; Motiyenko, R. A.; Müller, H. S. P.; Guillemin, J.-C.

    2017-05-01

    Context. A recently published astronomical detection of all three doubly 13C-substituted ethyl cyanides toward Sgr B2(N2) motivated us to investigate triple 13C isotopic species that are expected to be also present in the ISM. Aims: We aim to present an experimental study of the rotational spectrum of triple 13C-substituted ethyl cyanide, 13CH313CH213CN, in the frequency range 150-990 GHz. We want to use the determined spectroscopic parameters for searching for 13CH313CH213CN in ALMA data. The main objective of this work is to provide accurate frequency predictions to search for this molecule in the Galactic center source Sagittarius B2(N) and to facilitate its detection in space. Methods: The laboratory rotational spectrum of 13CH313CH213CN has been recorded with the Lille's fast DDS solid-state spectrometer between 150 GHz and 990 GHz. Results: More than 4000 rotational transitions were identified in the laboratory. The quantum numbers reach J = 115 and Ka = 39. Watson's Hamiltonian in the A and S reductions were used to analyze the spectra. Accurate spectroscopic parameters were determined. The rotational spectra of the 13C containing species CH3CH2CN have been assigned, thus allowing the determination of the rotational and centrifugal distortion constants Full Table 3 is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/601/A2

  11. Atmospheric chemistry of two biodiesel model compounds: methyl propionate and ethyl acetate.

    Science.gov (United States)

    Andersen, Vibeke F; Berhanu, Tesfaye A; Nilsson, Elna J K; Jørgensen, Solvejg; Nielsen, Ole John; Wallington, Timothy J; Johnson, Matthew S

    2011-08-18

    The atmospheric chemistry of two C(4)H(8)O(2) isomers (methyl propionate and ethyl acetate) was investigated. With relative rate techniques in 980 mbar of air at 293 K the following rate constants were determined: k(C(2)H(5)C(O)OCH(3) + Cl) = (1.57 ± 0.23) × 10(-11), k(C(2)H(5)C(O)OCH(3) + OH) = (9.25 ± 1.27) × 10(-13), k(CH(3)C(O)OC(2)H(5) + Cl) = (1.76 ± 0.22) × 10(-11), and k(CH(3)C(O)OC(2)H(5) + OH) = (1.54 ± 0.22) × 10(-12) cm(3) molecule(-1) s(-1). The chlorine atom initiated oxidation of methyl propionate in 930 mbar of N(2)/O(2) diluent (with, and without, NO(x)) gave methyl pyruvate, propionic acid, acetaldehyde, formic acid, and formaldehyde as products. In experiments conducted in N(2) diluent the formation of CH(3)CHClC(O)OCH(3) and CH(3)CCl(2)C(O)OCH(3) was observed. From the observed product yields we conclude that the branching ratios for reaction of chlorine atoms with the CH(3)-, -CH(2)-, and -OCH(3) groups are 9 ± 2%, respectively. The chlorine atom initiated oxidation of ethyl acetate in N(2)/O(2) diluent gave acetic acid, acetic acid anhydride, acetic formic anhydride, formaldehyde, and, in the presence of NO(x), PAN. From the yield of these products we conclude that at least 41 ± 6% of the reaction of chlorine atoms with ethyl acetate occurs at the -CH(2)- group. The rate constants and branching ratios for reactions of OH radicals with methyl propionate and ethyl acetate were investigated theoretically using transition state theory. The stationary points along the oxidation pathways were optimized at the CCSD(T)/cc-pVTZ//BHandHLYP/aug-cc-pVTZ level of theory. The reaction of OH radicals with ethyl acetate was computed to occur essentially exclusively (∼99%) at the -CH(2)- group. In contrast, both methyl groups and the -CH(2)- group contribute appreciably in the reaction of OH with methyl propionate. Decomposition via the α-ester rearrangement (to give C(2)H(5)C(O)OH and a HCO radical) and reaction with O(2) (to give CH(3)CH(2)C

  12. Clinical comparison of ethyl acetate and diethyl ether in the formalin-ether sedimentation technique.

    OpenAIRE

    Erdman, D D

    1981-01-01

    A substitute for the volatile solvent diethyl ether has been actively sought for the Formalin-ether sedimentation technique. Ethyl acetate has recently been shown to be a comparable substitute. In an effort to verify these findings and evaluate ethyl acetate under clinical conditions, comparison studies with 62 fresh human stool specimens were performed. Parallel concentrates with diethyl ether and ethyl acetate were prepared for each specimen, and the quantity and appearance of recovered par...

  13. A possible anti-inflammatory mechanism of ethyl acetate extracts of Teucrium stocksianum Bioss.

    Science.gov (United States)

    Mukarram Shah, Syed Muhammad

    2015-08-29

    Teucrium stocksianum (T. stocksianum) is one of the important members of the genus Teucrium which contains numerous biologically active compounds. Traditionally, it is used for the treatment of fever, pain, as expectorant and blood purifier. Researchers are trying to discover plants origin, novel and safe remedies for the management of various ailments. The present study was aimed to determine the possible anti-inflammatory mechanism of ethyl acetate extract of T. stocksianum. Preliminary, the ethanolic extract and sub-fractions were screened for anti-inflammatory potential at doses of 100, 200 and 300 mg/kg (i.p) body weight, using carrageenan induced paw edema test in mice. In-order to determine the possible mechanism of anti-inflammatory effect, the ethyl acetate fraction was ascertained with different phlogistic agents like histamine, bradykinin, prostaglandins E2 and arachedonic acid via paw edema test in mice. The ethanolic extract and sub-fractions of T. stocksianum displayed marked to moderate anti-inflammatory activity in a carrageenan induced paw edema test in mice. Among the sub-fractions, ethyl acetate fraction (EAF) demonstrated excellent (66%) anti-inflammatory action at the highest tested dose (300 mg/kg) that reached to the maximum value at 3rd hour after carrageenan injection and remained significant (***P<0.001) till 5th hour of test sample administration. EAF revealed moderate effect against the paw edema induced by histamine (31.048%) while non-significant results (18.148%) were observed against the edema induced by bradykinin. The extract demonstrated significant (66.23-73.076%) anti-inflammatory potential against the edematogenic effect of prostaglandin E2. Moreover, the extract also significantly inhibited (51.33%) the paw edema induced by arachedonic acid. Our results suggest that the EAF has dual action and produced the anti-inflammatory effect by blocking both pathways of arachedonic acid metabolites (cyclooxygenase and lipoxygenase). Thus

  14. Binding of ethyl pyruvate to bovine serum albumin: Calorimetric, spectroscopic and molecular docking studies

    Energy Technology Data Exchange (ETDEWEB)

    Pathak, Mallika [Department of Chemistry, Miranda House, University of Delhi, Delhi 11007 (India); Mishra, Rashmi; Agarwala, Paban K. [Department of Radiation Genetics and Epigenetics, Division of Radioprotective Drug Development Research, Institute of Nuclear Medicine and Allied Sciences, Delhi 110054 (India); Ojha, Himanshu, E-mail: himanshu.drdo@gmail.com [Department of Radiation Genetics and Epigenetics, Division of Radioprotective Drug Development Research, Institute of Nuclear Medicine and Allied Sciences, Delhi 110054 (India); Singh, Bhawna [Department of Radiation Genetics and Epigenetics, Division of Radioprotective Drug Development Research, Institute of Nuclear Medicine and Allied Sciences, Delhi 110054 (India); Singh, Anju; Kukreti, Shrikant [Nucleic Acid Research Laboratory, Department of Chemistry, University of Delhi, Delhi 11007 (India)

    2016-06-10

    Highlights: • ITC study showed binding of ethyl pyruvate with BSA with high binding affinity. • Ethyl pyruvate binding caused conformation alteration of BSA. • Fluorescence quenching mechanism is static in nature. • Electrostatic, hydrogen bonding and hydrophobic forces involved in binding. • Docking confirmed role of electrostatic, hydrogen bonding and hydrophobic forces. - Abstract: Various in vitro and in vivo studies have shown the anti-inflammatory and anticancer potential role of ethyl pyruvate. Bio-distribution of drugs is significantly influenced by the drug-serum protein binding. Therefore, the binding mechanism of the ethyl pyruvate with bovine serum albumin was investigated using UV–vis absorption, fluorescence, circular dichroism, isothermal titration calorimetry and molecular docking techniques. Absorption and fluorescence quenching studies indicated the binding of ethyl pyruvate with protein. Circular dichroism spectra of bovine serum albumin confirmed significant change in the conformation of protein upon binding. Thermodynamic data confirmed that ethyl pyruvate binds to bovine serum albumin at the two different sites with high affinity. Binding of ethyl pyruvate to bovine serum albumin involves hydrogen bonding, van der Waal and hydrophobic interactions. Further, docking studies indicated that ethyl pyruvate could bind significantly at the three binding sites. The results will definitely contribute to the development of ethyl pyruvate as drug.

  15. STABILITY OF ETHYL ACETATE IN WHOLE BLOOD DURING STORAGE UNDER VARIOUS CONDITIONS

    OpenAIRE

    Watanabe, Kanako; Ishii, Akira; Seno, Hiroshi; Kumazawa, Takeshi; Suzuki, Osamu; Suzuki, Kanako

    2000-01-01

    Various conditions of storage have been tested for stability of ethyl acetate in whole blood. Ethyl acetate (5μg/ml) was spiked to whole blood, and kept at room temperature or at 4℃ for various intervals in the presence or absence of sodium fluoride. Ethyl acetate and ethanol were simultaneously measured by our cryogenic oven trapping gas chromatography. Ethyl acetate was found stable at room temperature for 3 days in the presence of 10 mg sodium azide and 50 mg sodium fluoride in 1 ml whole ...

  16. Mixture effects during the oxidation of toluene, ethyl acetate and ethanol over a cryptomelane catalyst.

    Science.gov (United States)

    Santos, V P; Pereira, M F R; Órfão, J J M; Figueiredo, J L

    2011-01-30

    The catalytic oxidation of two-component VOC mixtures (ethanol, ethyl acetate and toluene) was studied over cryptomelane. Remarkable mixture effects were observed on the activity and the selectivity. Toluene inhibits both ethyl acetate and ethanol oxidation, this effect being more evident in the case of ethyl acetate. For instance, the temperature for 100% conversion is about 210 °C when ethyl acetate is oxidised alone, and 250 °C or higher, when it is oxidised in mixtures with toluene. On the contrary, toluene oxidation is only slightly inhibited by the presence of ethyl acetate, while the presence of ethanol has a promoting effect. Concerning the mixtures of ethyl acetate and ethanol, both compounds have a mutual inhibitory effect, which is more evident in the case of ethyl acetate (the temperature for 100% conversion of ethyl acetate is about 45 °C higher when ethyl acetate is oxidised in mixtures with ethanol, while in the case of ethanol the corresponding increase is only 10 °C). Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Growth of glycine ethyl ester hydrochloride and its characterizations

    Energy Technology Data Exchange (ETDEWEB)

    Venkatesan, G.; Pari, S., E-mail: sparimyur@gmail.com

    2016-11-15

    Single crystal of glycine ethyl ester hydrochloride by slow evaporation method is reported. The grown crystal characterized by single crystal X-ray diffraction, FT-IR, UV–Vis–NIR and fluorescence spectroscopy. It is established that the crystal falls under the monoclinic system and space group P21/c with the cell parameters as: a=8.565 Å, b=12.943 Å, c=6.272 Å, α=γ=90°, β=103.630º. UV–Vis–NIR spectrum shows indirect allowed transition with a band gap of 5.21 eV and other optical properties are measured. The crystal is also shown to have a high transmittance in the visible region. The third order nonlinear property and optical limiting have been investigated using Z-Scan technique. Complex impedance spectrum measured at the dc conductivity. Dependence of dielectric constant, dielectric loss and ac conductivity on frequency at different temperature of applied ac field is analyzed. The mechanical behavior has been assessed by Vickers microhardness indenter. The thermal behavior of glycine ethyl ester hydrochloride was analyzed using TG/DTA thermal curves. From the thermal study, the material was found to possess thermal stability up to 174 °C. The predicted NLO properties, UV–Vis transmittance and Z-scan studies indicate that is an attractive material for photonics optical limiting applications.

  18. On the high-temperature unimolecular decomposition of ethyl levulinate

    KAUST Repository

    Alabbad, Mohammed

    2016-09-20

    The pyrolysis of ethyl levulinate (EL) was studied behind reflected shock waves over the temperature range of 1015-1325K and pressures of 750-1650Torr. The reaction progress was followed by measuring ethylene mole fraction using CO2 gas laser absorption near 10.532 μm. The rate coefficients for the unimolecular dissociation of EL were extracted from the initial slope method and further ascertained by using a complete kinetic model. Our data exhibited no discernible pressure dependence under the current experimental conditions. To rationalize our results further, high-level quantum chemical and master equation calculations were employed to calculate the pressure- and temperature-dependence of the reaction. Our calculations revealed that unimolecular dissociation of EL involves simultaneous 1,5-hydrogen shift of the β-hydrogen to the carbonyl group, rupture of the O-C ester bond and formation of the π-bond (C α -C β ). Our results present evidences that the C2H4 elimination from EL occurs in a concerted manner. To our knowledge, this work represents the first experimental and theoretical study of the thermal unimolecular dissociation of ethyl levulinate. © 2016 The Combustion Institute.

  19. DISCOVERY OF METHYL ACETATE AND GAUCHE ETHYL FORMATE IN ORION

    Energy Technology Data Exchange (ETDEWEB)

    Tercero, B.; Cernicharo, J.; Lopez, A.; Caro, G. M. Munoz [Department of Astrophysics, CAB, INTA-CSIC, Crta Torrejon-Ajalvir, km. 4, E-28850 Torrejon de Ardoz, Madrid (Spain); Kleiner, I.; Nguyen, H. V. L., E-mail: terceromb@cab.inta-csic.es, E-mail: jcernicharo@cab.inta-csic.es, E-mail: lopezja@cab.inta-csic.es, E-mail: munozcg@cab.inta-csic.es, E-mail: isabelle.kleiner@lisa.u-pec.fr, E-mail: nguyen@pc.rwth-aachen.de [Laboratoire Interuniversitaire des Systemes Atmospheriques, CNRS/IPSL UMR7583 et Universites Paris Diderot et Paris Est, 61 av. General de Gaulle, F-94010 Creteil (France)

    2013-06-10

    We report on the discovery of methyl acetate, CH{sub 3}COOCH{sub 3}, through the detection of a large number of rotational lines from each one of the spin states of the molecule: AA species (A{sub 1} or A{sub 2}), EA species (E{sub 1}), AE species (E{sub 2}), and EE species (E{sub 3} or E{sub 4}). We also report, for the first time in space, the detection of the gauche conformer of ethyl formate, CH{sub 3}CH{sub 2}OCOH, in the same source. The trans conformer is also detected for the first time outside the Galactic center source SgrB2. From the derived velocity of the emission of methyl acetate, we conclude that it arises mainly from the compact ridge region with a total column density of (4.2 {+-} 0.5) Multiplication-Sign 10{sup 15} cm{sup -2}. The derived rotational temperature is 150 K. The column density for each conformer of ethyl formate, trans and gauche, is (4.5 {+-} 1.0) Multiplication-Sign 10{sup 14} cm{sup -2}. Their abundance ratio indicates a kinetic temperature of 135 K for the emitting gas and suggests that gas-phase reactions could participate efficiently in the formation of both conformers in addition to cold ice mantle reactions on the surface of dust grains.

  20. Thermal Breakdown Kinetics of 1-Ethyl-3-Methylimidazolium Ethylsulfate Measured Using Quantitative Infrared Spectroscopy.

    Science.gov (United States)

    Wheeler, Jeffrey L; Pugh, McKinley; Atkins, S Jake; Porter, Jason M

    2017-12-01

    In this work, the thermal stability of the room temperature ionic liquid (RTIL) 1-ethyl-3-methylimidazolium ethylsulfate ([EMIM][EtSO4]) is investigated using infrared (IR) spectroscopy. Quantitative IR absorption spectral data are measured for heated [EMIM][EtSO4]. Spectra have been collected between 25 ℃ and 100 ℃ using a heated optical cell. Multiple samples and cell pathlengths are used to determine quantitative values for the molar absorptivity of [EMIM][EtSO4]. These results are compared to previous computational models of the ion pair. These quantitative spectra are used to measure the rate of thermal decomposition of [EMIM][EtSO4] at elevated temperatures. The spectroscopic measurements of the rate of decomposition show that thermogravimetric methods overestimate the thermal stability of [EMIM][EtSO4].

  1. Fatty acid ethyl ester synthesis in the preparation of scotch whiskey.

    Science.gov (United States)

    Goss, K A; Alharethi, R; Laposata, M

    1999-04-01

    Fatty acid ethyl esters (FAEE), nonoxidative ethanol metabolites present in human organs commonly damaged by ethanol abuse, have been implicated as mediators of organ damage. FAEE are additives in various foods and beverages to provide flavor or fragrance, and therefore are common dietary lipid constituents. We hypothesized that FAEE could be generated during alcoholic beverage production because fatty acids are present within microorganisms and ethanol is generated during the fermentation process. In this report, we demonstrate that FAEE are present in commercially available scotch beverages, and that in the preparation of scotch, FAEE can be produced during the fermentation reaction as a result of FAEE synthase activity in the yeast. Following ingestion of scotch, preformed FAEE are delivered to GI tract. The consequences of ingestion of FAEE in scotch, if any, remain to be determined.

  2. Effects of wildlife of ethyl and methyl parathion applied to California USA rice fields

    Science.gov (United States)

    Custer, T.W.; Hill, E.F.; Ohlendorf, H.M.

    1985-01-01

    Selected rice fields on the Sacramento National Wildlife Refuge Complex were aerially sprayed one time during May or June 1982 with either ethyl (0.11 kg Al/ha) or methyl (0.84 kg AI/ha) parathion for control of tadpole shrimp, Triops longicaudatus. No sick or dead vertebrate wildlife were found or adjacent to the treated rice fields after spraying. Specimens of the following birds and mammals were assayed for brain cholinesterase (ChE) activity to determine exposure to either form of parathion; house mouse, Mus musculus; black-tailed jackrabbit, Lepus californicus; mallard, Anas platyrhynchos; ring-necked pheasant, Phasianus colchicus; American coot, Fulica americana; and red-winged blackbird, Agelaius phoeniceus. Both mice and pheasants from methyl parathion-treated fields had overall mean ChE activities that were significantly (P fields, but sufficient information on potential hazards was obtained to warrant caution in use of these chemicals, especially methyl parathion, in rice fields.

  3. Effects on wildlife of ethyl and methyl parathion applied to California rice fields

    Science.gov (United States)

    Custer, T.W.; Hill, E.F.; Ohlendorf, H.M.

    1985-01-01

    Selected rice fields on the Sacramento National Wildlife Refuge Complex were aerially sprayed one time during May or June 1982 with either ethyl (0.11 kg Al/ha) or methyl (0.84 kg AI/ha) parathion for control of tadpole shrimp, Triops longicaudatus. No sick or dead vertebrate wildlife were found or adjacent to the treated rice fields after spraying. Specimens of the following birds and mammals were assayed for brain cholinesterase (ChE) activity to determine exposure to either form of parathion; house mouse, Mus musculus; black-tailed jackrabbit, Lepus californicus; mallard, Anas platyrhynchos; ring-necked pheasant, Phasianus colchicus; American coot, Fulica americana; and red-winged blackbird, Agelaius phoeniceus. Both mice and pheasants from methyl parathion-treated fields had overall mean ChE activities that were significantly (P fields, but sufficient information on potential hazards was obtained to warrant caution in use of these chemicals, especially methyl parathion, in rice fields.

  4. Placental Fatty Acid ethyl esters are elevated with maternal alcohol use in pregnancies complicated by prematurity.

    Directory of Open Access Journals (Sweden)

    Theresa W Gauthier

    Full Text Available The accumulation of fatty acid ethyl esters (FAEEs in meconium of term newborns has been described as one potential biomarker of maternal alcohol use during pregnancy. FAEEs accumulate in multiple alcohol-exposed fetal tissues and in the placenta. Limited research has focused on the identification of the premature newborn exposed to alcohol in utero. We hypothesized that maternal alcohol use occurs in a significant proportion of premature deliveries and that this exposure can be detected as elevated placental FAEEs. The goals of this study were to 1 determine the prevalence of maternal alcohol use in the premature newborn and 2 investigate whether placental FAEEs could identify those newborns with fetal alcohol exposure. This prospective observational study evaluated 80 placentas from 80 women after premature delivery. Subjects were interviewed for alcohol intake and placental FAEEs were quantified via GC/MS. Receiver Operator Characteristic (ROC Curves were generated to evaluate the ability of placental FAEEs to predict maternal drinking during pregnancy. Adjusted ROC curves were generated to adjust for gestational age, maternal smoking, and illicit drug use. 30% of the subjects admitted to drinking alcohol during pregnancy and approximately 14% answered questions indicative of problem drinking (designated AUDIT+. The specific FAEEs ethyl stearate and linoleate, as well as combinations of oleate + linoleate + linolenate (OLL and of OLL + stearate, were significantly (p<0.05 elevated in placentas from AUDIT+ pregnancies. Adjusted ROC Curves generated areas under the curve ranging from 88-93% with negative predictive values of 97% for AUDIT+ pregnancies. We conclude that nearly one third of premature pregnancies were alcohol-exposed, and that elevated placental FAEEs hold great promise to accurately determine maternal alcohol use, particularly heavy use, in pregnancies complicated by premature delivery.

  5. Pharmacokinetic comparison between quercetin and quercetin 3-O-β-glucuronide in rats by UHPLC-MS/MS

    Science.gov (United States)

    Yang, Le-Le; Xiao, Na; Li, Xiao-Wei; Fan, Yong; Alolga, Raphael N.; Sun, Xiao-Yue; Wang, Shi-Lei; Li, Ping; Qi, Lian-Wen

    2016-10-01

    Quercetin is a natural flavonoid widely distributed in human diet and functional foods. Quercetin 3-O-β-glucuronide (Q3G) is present in wine and some medicinal plants. Quercetin and Q3G may be metabolized from each other in vivo. While quercetin has been the subject of many studies, the pharmacokinetic profiles of quercetin and Q3G (in animals) have not yet been compared. Herein, we prepared a column-based method for rapid isolation of Q3G from Nelumbo nucifera. Then, we developed an UHPLC-MS/MS method to compare the pharmacokinetics of quercetin and Q3G. Our results showed that the plasma concentration-time curves of quercetin and Q3G show two maxima (Tmax1 ≈ 0.75 h, Tmax2 ≈ 5 h). After oral administration of 100 mg/kg quercetin or 100 mg/kg Q3G in rats, predominantly Q3G was detected in plasma with AUC at 39529.2 ± 6108.2 mg·h·L-1 or 24625.1 ± 1563.8 mg·h·L-1, 18-fold higher than quercetin with AUC at 1583.9 ± 583.3 mg·h·L-1 or 1394.6 ± 868.1 mg·h·L-1, respectively. After intravenous injection of 10 mg/kg in rats, Q3G showed extensive tissue uptake in kidney (409.2 ± 118.4 ng/g), liver (166.1 ± 52.9 ng/g), heart (97.7 ± 22.6 ng/g), and brain (5.8 ± 1.2 ng/g). In conclusion, we have shown that Q3G is a major active component in plasma and tissue for oral administration of quercetin or Q3G.

  6. Radiolabeling of bleomycin-glucuronide with (131)I and biodistribution studies using xenograft model of human colon tumor in Balb/C mice.

    Science.gov (United States)

    Demiroğlu, Hasan; Avcibaşi, Ugur; Ünak, Perihan; Müftüler, Fazilet Zümrüt Biber; İçhedef, Ç A; Gümüşer, Fikriye Gül; Sakarya, Serhan

    2012-08-01

    Bleomycin-glucuronide (BLMG) is the glucuronide conjugate of BLM. In the present study, BLMG was primarily enzymatically synthesized by using a microsome preparate separated from rat liver, labeled with (131)I by iodogen method with the aim of generating a radionuclide-labeled prodrug, and investigated its bioaffinities with tumor-bearing Balb/C mice. Quality control procedures were carried out using thin-layer radiochromatography and high-performance liquid chromatography. Tumor growing was carried out by following Caco-2 cell inoculation into mice. Radiolabeling yield was found to be about 65%. Results indicated that (131)I-labeled BLMG ((131)I-BLMG) was highly stable for 24 hours in human serum. Biodistribution studies were carried out with male Albino Wistar rats and colorectal adenocarcinoma tumor-bearing female Balb/C mice. The biodistribution results in rats showed high uptake in the prostate, the large intestine, and the spinal cord. In addition to this, scintigraphic results agreed with those of biodistributional studies. Xenography studies with tumor-bearing mice demonstrated that tumor uptakes of (131)I-BLM and (131)I-BLMG were high in the first 30 minutes postinjection. Tumor-bearing animal studies demonstrated that (131)I-BLMG was specially retained in colorectal adenocarcinoma with high tumor uptake. Therefore, (131)I-BLMG can be proven to be a promising imaging and therapeutic agent, especially for colon cancer in nuclear medical applications.

  7. Electrochemical investigation of cold worked copper in alkaline solution with the presence of potassium ethyl xanthate

    Directory of Open Access Journals (Sweden)

    Ivanov Svetlana Lj.

    2014-01-01

    Full Text Available This paper presents the investigation results of the electrochemical behavior of copper in 1 M Na2CO3 solution in the presence of potassium ethyl xanthate (KEtX with different concentrations. Tests were conducted on copper samples obtained without deformation and with deformation of 83, 91 and 99 %. Samples were obtained by cold drawing of wire, which was previously obtained by dip-forming procedure. Corrosion behavior of cold deformed copper wire is characterized by its open circuit potential and behavior during anodic polarization. Experiments were carried out in aqueous solution 1 M Na2CO3 with added various amounts of KEtX between 0.008 g/l and 0.15 g/l. It was experimentally proved that the degree of deformation between 83 and 99 % does not have a large effect on the open circuit potential, as well as on the behavior of copper during anodic polarization in 1 M Na2CO3. Voltammograms show no significant differences between peak heights obtained for different electrodes. The first peak which occurs at potential of around -0.06 V vs. SCE corresponds to the formation of copper oxide Cu2O. The second wide peak is at potential of around 0.15 V vs. SCE and corresponds to the formation of CuO. Addition of potassium ethyl xanthate in alkaline 1 M Na2CO3 solution changes the mechanism of the process in anodic part, which is reflected in the change of shape of voltammograms. In presence of KEtX in concentration between 0.008 g/l and 0.15 g/l on voltammograms a sharp peak appears at potential of about -0.2 V vs. SCE and corresponds to the oxidation of xanthate. Current density, which determines the rate of the process which takes place at the electrode surface, yet in the presence of smallest amounts of KEtX (<0,08 g/l is higher than in the absence of KEtX. It allows one to conclude that the processes of oxidation of copper accelerate in presence of potassium ethyl xanthate.

  8. Catalytic distillation to remove minute amount of ethyl acetate in aqueous ethanol solution; Ethanol suiyoekichu no biryo no sakusan ethyl no jokyo ni taisuru shokubai joryu no shiko

    Energy Technology Data Exchange (ETDEWEB)

    Ikari, A.; Hatate, Y.; Aiko, R. [Kagoshima University, Kagoshima (Japan)

    1997-07-10

    Pillow-type packings were prepared by wrapping ion exchange resin with stainless steel wire netting. An experimental apparatus for batch distillation was constructed, in which 60 packings were packed. Aqueous ethanol solutions containing a minute amount of ethyl acetate were changed in the still and distilled. When all the condensed top vapor was returned to the column, the concentration of ethyl acetate in distillate decreased rapidly, and the concentration of acetic acid in the still increased gradually. On the contrary, when the aqueous ethanol solution containing a minute amount of acetic acid was distilled, ethyl acetate was produced in the column, and its concentration in distillate increased gradually. From these experimental results, the applicability of catalytic distillation for removing a minute amount of ethyl acetate in aqueous ethanol solution is discussed. 5 refs., 4 figs., 1 tab.

  9. Simultaneous exposure to ethyl benzene and noise : synergistic effects on outer hair cells

    NARCIS (Netherlands)

    Cappaert, N.L.M.; Klis, S.F.L.; Muijser, H.; Kulig, B.M.; Smoorenburg, G.F.

    2001-01-01

    The effects on hearing of simultaneous exposure to the ototoxic organic solvent ethyl benzene and broad-band noise were evaluated in rats. The effects of three ethyl benzene concentrations (0, 300 or 400 ppm) and three noise levels (95 or 105 dBlin SPL or background noise at 65 dBlin SPL) and all

  10. Differential susceptibility of rats and guinea pigs to the ototoxic effects of ethyl benzene

    NARCIS (Netherlands)

    Cappaert, NLM; Klis, SFL; Muijser, H; Kulig, BM; Ravensberg, LC; Smoorenburg, GF

    2002-01-01

    The present study was designed to compare the ototoxic effects of volatile ethyl benzene in guinea pigs and rats. Rats showed deteriorated auditory thresholds in the mid-frequency range, based on electrocochleography, after 550-ppm ethyl benzene (8 h/day, 5 days). Outer hair cell (OHC) loss was

  11. The direct transformation of ethanol to ethyl acetate over Cu/SiO2 ...

    Indian Academy of Sciences (India)

    key factor to achieve direct transformation of ethanol to ethyl acetate. Keywords. Ethanol; ethyl acetate; copper .... Pyridine adsorption Fourier transform infrared spectrum was performed according to literature.24 ..... Ji Chan Park H J L, Jung Up Bang, Kang Hyun Park and. Hyunjoon Song 2009 Chem. Commun. 7345. 8.

  12. 46 CFR 151.50-40 - Additional requirements for carbon disulfide (carbon bisulfide) and ethyl ether.

    Science.gov (United States)

    2010-10-01

    ... bisulfide) and ethyl ether. 151.50-40 Section 151.50-40 Shipping COAST GUARD, DEPARTMENT OF HOMELAND... ether. (a) The provisions of this section are applicable if specifically referenced in the Special... disulfide (carbon bisulfide) and § 151.50-42 for ethyl ether shall also be observed. ...

  13. Synthesis, Analgesic and Anti-inflammatory Activities of 3- Ethyl-2 ...

    African Journals Online (AJOL)

    4(3H)-ones and evaluate them for their analgesic and anti-inflammatory activities. Methods: The compounds, 3-ethyl-2-substituted amino-quinazolin-4(3H)-ones, were synthesized by reacting the amino group of 3-ethyl-2-hydrazino ...

  14. Poly (N-ethyl aniline)/Ag Nanocomposite as Humidity Sensor

    Science.gov (United States)

    Pande, Nishigandh S.; Jaspal, Dipika; Ambekar, Jalindar

    Poly (N-ethyl aniline)/Ag organic-inorganic composite has been synthesized by a single step in situ chemical oxidative polymerization method. The synthesis of Poly (N-ethyl aniline)/Ag nanocomposite has been confirmed by X-ray diffraction (XRD), Ultraviolet-Vis Spectroscopy (UV-visible), Fourier transform infrared analysis (FTIR) and FE-SEM investigations. XRD spectral study exhibited major diffraction in the range 20-80∘ (2θ) and indicated the semicrystalline nature of poly (N-ethyl aniline)/Ag nanocomposite. Characteristic peaks in UV-visible and FTIR spectra of poly (N-ethyl aniline) switched to higher wave numbers in poly (N-ethyl aniline)/Ag nanocomposite. Peaks at 1789cm-1, 1595cm-1, 667cm-1 and 501cm-1 in FTIR spectrum confirmed the formation of poly (N-ethyl aniline)/Ag nanocomposite. FE-SEM photographs reported agglomerated granular particulate nature of poly (N-ethyl aniline)/Ag nanocomposite. Synthesized poly (N-ethyl aniline)/Ag nanocomposite exhibited a high response to humidity, good reproducibility and stability at room temperature. An appreciable response was shown in the presence of 40% humid atmosphere for up to successive four cycles. Composite sensitivity has been found to increase with the increasing concentration of humidity, at room temperature.

  15. Chemical constituents of the ethyl acetate extracts of the stem bark ...

    African Journals Online (AJOL)

    The antibacterial activities of ethyl acetate, methanol and aqueous extracts of the stem bark of Dichrostachys cinerea and the roots of Parkia bicolor have been evaluated. Ethyl acetate extracts have been investigated, studies that led to a series of known compounds, amongst which many are reported here for the very first ...

  16. High-temperature unimolecular decomposition of ethyl propionate

    KAUST Repository

    Giri, Binod

    2016-10-09

    This work reports rate coefficients of the thermal unimolecular decomposition reaction of ethyl propionate (EP) behind reflected shock waves over the temperature range of 976–1300 K and pressures of 825–1875 Torr. The reaction progress was monitored by detecting CH near 10.532 μm using CO gas laser absorption. In addition, G3//MP2/aug-cc-pVDZ and master equation calculations were performed to assess the pressure- and temperature-dependence of the reaction. Our calculations revealed that CH elimination occurs via a six-centered retro-ene transition state. Our measured rate data are close to the high-pressure limit and showed no discernable temperature fall off.

  17. Icosapent ethyl for the treatment of severe hypertriglyceridemia

    Directory of Open Access Journals (Sweden)

    Fares H

    2014-06-01

    Full Text Available Hassan Fares,1 Carl J Lavie,2,3 James J DiNicolantonio,4 James H O'Keefe,5 Richard V Milani2 1Department of Hospital Medicine, Ochsner Medical Center, New Orleans, LA, 2Department of Cardiovascular Diseases, John Ochsner Heart and Vascular Institute, Ochsner Clinical School, University of Queensland School of Medicine, New Orleans, LA, 3Department of Preventive Medicine, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, 4Mid America Heart Institute at Saint Luke's Hospital, Kansas City, MO, 5Mid America Heart Institute, University of Missouri–Kansas City, Kansas City, MO, USA Abstract: Hypertriglyceridemia is a highly prevalent lipid abnormality and it is associated with atherosclerosis, with a growing body of evidence linking elevated triglycerides (TGs with cardiovascular disease. The current major omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA/docosahexaenoic acid (DHA combination, lowers serum TGs while often increasing levels of low-density lipoprotein cholesterol. Icosapent ethyl is an omega-3 polyunsaturated fatty acid with a 96% pure ethyl ester of EPA that has been recently approved for lowering TG levels in patients with very high TGs (≥500 mg/dL, and it does so without significantly affecting serum low-density lipoprotein cholesterol. The potential benefits of omega-3 fatty acid therapy for dyslipidemias will be discussed, including the potential pros and cons of EPA alone versus the more common and readily available EPA/DHA combination therapy. Keywords: triglycerides, low-density lipoprotein, eicosapentaenoic acid, docosahexaenoic acid

  18. Master equation description of the multiphoton decomposition of ethyl acetate

    Science.gov (United States)

    Eberhardt, J. E.; Knott, R. B.; Pryor, A. W.; Gilbert, Robert G.

    1982-07-01

    In experimental observations of the multiphoton decomposition of ethyl acetate by a CO 2 laser at 1045.0 cm -1 fluences up to 4 J cm -2 were employed to dissociate 2 Pa of ethyl acetate in up to 600 Pa of N 2, He, Ne, Ar, Kr, Xe, ethylene and acetone bath gases. The fraction dissociated was measured in a closed cell, either by rate of removal of reactant, monitored by a probe laser and spectrophone, or by rate of pressure rise, monitored by a capacitance manometer. Total absorption and transient absorption changes were also measured in separate experiments. Data were analysed by finite difference solution of the energy-grained master equation, incorporating collisional effects and changes in transitional temperature. The convergence of the solutions was checked with decrease in the size of the energy grain. Microscopic reaction rates were described by an RRKM formulation with parameters from thermal experiments. Radiation absorption was described by an energy-dependent cross section with one free parameter chosen to match independent data. The collisional energy transfer function was an exponential form with the mean down transfer energy as a parameter. Dissociation versus pressure and fluence was fitted by one value of for each bath gas: N 2-820, He-550, Ne-700, Ar-930, Kr-905, Xe-920, C 2H 4-3000, CO(CH 3) 2-5000 cm -1. The technique appears to be a reliable means of obtaining energy transfer data at low temperatures. In addition to the experiments with reactant diluted in bath gas, the decomposition of undiluted reactant was also observed, at pressures in the range 1 to 800 Pa; here, reaction was terminated by collisions of irradiated molecules with molecules outside the beam; an approximate theory which appears to confirm the hypotheses is presented.

  19. Crystal structure of azilsartan methyl ester ethyl acetate hemisolvate

    Directory of Open Access Journals (Sweden)

    Zhengyi Li

    2015-02-01

    Full Text Available The title compound, C26H22N4O5 (systematic name: methyl 2-ethoxy-1-{4-[2-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-ylphenyl]benzyl}-1H-1,3-benzodiazole-7-carboxylate ethyl acetate hemisolvate, was obtained via cyclization of methyl (Z-2-ethoxy-1-{(2′-(N′-hydroxycarbamimidoyl-[1,1′-biphenyl]-4-ylmethyl}-1H-benzo[d]imidazole-7-carboxylate with diphenyl carbonate. There are two independent molecules (A and B with different conformations and an ethyl acetate solvent molecule in the asymmetric unit. In molecule A, the dihedral angle between the benzene ring and its attached oxadiazole ring is 59.36 (17; the dihedral angle between the benzene rings is 43.89 (15 and that between the benzene ring and its attached imidazole ring system is 80.06 (11°. The corresponding dihedral angles in molecule B are 58.45 (18, 50.73 (16 and 85.37 (10°, respectively. The C—O—C—Cm (m = methyl torsion angles for the ethoxy side chains attached to the imidazole rings in molecules A and B are 93.9 (3 and −174.6 (3°, respectively. In the crystal, the components are linked by N—H...N and C—H...O hydrogen bonds, generating a three-dimensional network. Aromatic π–π stacking interactions [shortest centroid–centroid separation = 3.536 (3Å] are also observed.

  20. Crystal structure of azilsartan methyl ester ethyl acetate hemisolvate.

    Science.gov (United States)

    Li, Zhengyi; Liu, Rong; Zhu, Meilan; Chen, Liang; Sun, Xiaoqiang

    2015-02-01

    The title compound, C26H22N4O5 (systematic name: methyl 2-eth-oxy-1-{4-[2-(5-oxo-4,5-di-hydro-1,2,4-oxa-diazol-3-yl)phenyl]benz-yl}-1H-1,3-benzo-diazole-7-carboxyl-ate ethyl acetate hemisolvate), was obtained via cyclization of methyl (Z)-2-eth-oxy-1-{(2'-(N'-hy-droxy-carbamimido-yl)-[1,1'-biphen-yl]-4-yl)meth-yl}-1H-benzo[d]imidazole-7-carboxyl-ate with diphen-yl carbonate. There are two independent mol-ecules (A and B) with different conformations and an ethyl acetate solvent mol-ecule in the asymmetric unit. In mol-ecule A, the dihedral angle between the benzene ring and its attached oxa-diazole ring is 59.36 (17); the dihedral angle between the benzene rings is 43.89 (15) and that between the benzene ring and its attached imidazole ring system is 80.06 (11)°. The corres-ponding dihedral angles in mol-ecule B are 58.45 (18), 50.73 (16) and 85.37 (10)°, respectively. The C-O-C-Cm (m = meth-yl) torsion angles for the eth-oxy side chains attached to the imidazole rings in mol-ecules A and B are 93.9 (3) and -174.6 (3)°, respectively. In the crystal, the components are linked by N-H⋯N and C-H⋯O hydrogen bonds, generating a three-dimensional network. Aromatic π-π stacking inter-actions [shortest centroid-centroid separation = 3.536 (3)Å] are also observed.

  1. Antidepressant-like effect of Kyllinga brevifolia rhizomes in male mice and chemical characterization of the components of the active ethyl acetate fraction.

    Science.gov (United States)

    Hellión-Ibarrola, M C; Montalbetti, Y; Heinichen, O Y; Kennedy, M L; Campuzano, M A; Alvarenga, N; Ibarrola, D A

    2016-12-24

    days) was similar to imipramine. The main constituents of the KbF-ethyl-ac were identified as catechins and their dimers by LC-DAD-ESI-MS and LC-ESI-MS/MS, according to their UV and MS spectra, as compared with the literature data. These results indicate an important antidepressant-like profile of action for the CEKb and KbF-ethyl-ac; and meanwhile, this effect may partially reside on catechins and their dimers isolated from the KbF-ethyl-ac. These findings indicate that K. brevifolia exerts antidepressant -like effects in mice and suggest its potential usefulness for the treatment of depression in humans and encourage us to pursue the isolation of the molecules associated to the effect observed in CEKb and KbF-ethyl-ac, and to determine the mechanism of antidepressant-like effect of Kyllinga brevifolia using adequate complementary test. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Preconditioning with ethyl 3,4-dihydroxy benzoate augments aerobic respiration in rat skeletal muscle

    Directory of Open Access Journals (Sweden)

    Nimker C

    2016-05-01

    Full Text Available Charu Nimker, Deependra Pratap Singh, Deepika Saraswat, Anju Bansal Experimental Biology Division, Defence Institute of Physiology and Allied Sciences, Defense Research and Development Organisation, Timarpur, Delhi, India Abstract: Muscle respiratory capacity decides the amount of exertion one's skeletal muscle can undergo, and endurance exercise is believed to increase it. There are also certain preconditioning methods by which muscle respiratory and exercise performance can be enhanced. In this study, preconditioning with ethyl 3,4-dihydroxybenzoate (EDHB, a prolyl hydroxylase domain enzyme inhibitor, has been investigated to determine its effect on aerobic metabolism and bioenergetics in skeletal muscle, thus facilitating boost in physical performance in a rat model. We observed that EDHB supplementation increases aerobic metabolism via upregulation of HIF-mediated GLUT1 and GLUT4, thus enhancing glucose uptake in muscles. There was also a twofold rise in the activity of enzymes of tricarboxylic acid (TCA cycle and glycolysis, ie, hexokinase and phosphofructokinase. There was an increase in citrate synthase and succinate dehydrogenase activity, resulting in the rise in the levels of ATP due to enhanced Krebs cycle activity as substantiated by enhanced acetyl-CoA levels in EDHB-treated rats as compared to control group. Increased lactate dehydrogenase activity, reduced expression of monocarboxylate transporter 1, and increase in monocarboxylate transporter 4 suggest transport of lactate from muscle to blood. There was a concomitant decrease in plasma lactate, which might be due to enhanced transport of lactate from blood to the liver. This was further supported by the rise in liver pyruvate levels and liver glycogen levels in EDHB-supplemented rats as compared to control rats. These results suggest that EDHB supplementation leads to improved physical performance due to the escalation of aerobic respiration quotient, ie, enhanced muscle

  3. The effect of ethyl cyanoacrylate on experimental posterior lateral spinal fusion in a rat model.

    Science.gov (United States)

    Gezici, Ali Riza; Ergün, Rüçhan; Yilmaz, Fahri; Gürel, Kamil

    2009-01-01

    Cyanoacrylates (CAs) are a type of tissue adhesives which are currently the most commonly used for cutaneous closings. The use of CAs was reported in other clinical procedures such as odontology, neurological surgery, maxillary surgery, orthopaedics, plastic surgery, etc. In this experimental study the authors carried out posterolateral spinal fusion in a rat model to test the usefulness of ethyl-cyanoacrylate (ECA) in fixation of allograft/autograft fusions. 25 Sprague-Dawley rats were randomized into two study groups. Bilateral posterolateral lumbar intertransverse process spinal fusion was performed with both autograft and allograft in both groups. ECA gel was dropped in the fusion area in a rat model in group II. The fusion rates as determined by manual palpation were 75% in controls and 46% in the ECA group (p = 0.322). According to radiographic score, the spinal segment was considered to be fused radiographically in 66% of controls and in 46% of animals in the ECA group (p = 0.43). The mean histological scores were 5.58 +/- 0.14 and 4.53 +/- 0.18 for the control and treatment group, respectively (p = 0.001). The mean bone density of the fusion masses was 101.3 +/- 2.5 in the control group and 92.0 +/- 3.3 in the ECA treatment group (p = 0.044). Ethyl-cyanoacrylate appeared to retard the osteogenic fusion but was well tolerated and did not induce necrosis, allergic reaction, infection, necrosis or neurological deficit in a rat model of posterolateral spinal fusion.

  4. Telotristat ethyl: proof of principle and the first oral agent in the management of well-differentiated metastatic neuroendocrine tumor and carcinoid syndrome diarrhea.

    Science.gov (United States)

    Masab, Muhammad; Saif, Muhammad Wasif

    2017-12-01

    Metastatic neuroendocrine tumors (NETs) are associated with carcinoid syndrome that is typically characterized by diarrhea, cutaneous flushing and bronchospasm. Treatment with somatostatin analogues (SSA) improves the symptom burden but a significant proportion of patients stop responding to SSA therapy eventually. Novel agents with the potential to effectively control the symptoms are urgently needed. This article reviews an in-depth analysis of the phase I-III clinical trials determining the clinical rationale for the use of tryptophan hydroxylase inhibitor, telotristat ethyl in patients with well-differentiated metastatic NETs and uncontrolled carcinoid syndrome. Telotristat ethyl has already been approved for the treatment of inadequately controlled carcinoid syndrome symptoms in metastatic NET patients on SSA therapy. Results from multiple phase I-III clinical studies of telotristat ethyl therapy have reported a significant decrease in the daily bowel movement frequency, increase in quality of life and the subsequent decrease in annual health costs related to carcinoid syndrome symptoms in NET patients. The associated decrease in urinary 5-hydroxyindoleacetic acid (u5-HIAA) provides evidence that telotristat ethyl effectively decreases serotonin production, and therefore, offers a rationale to investigate this agent to mitigate serotonin-mediated complications in this patient population, especially cardiac valvular disease or mesenteric fibrosis.

  5. Two Isophalerin Compounds from Ethyl Acetate of Leave and Fruit of Mahkota Dewa (Phaleria macrocarpa (Scheff. Boerl. and Its Antibacterial Activity

    Directory of Open Access Journals (Sweden)

    Susilawati Susilawati

    2015-07-01

    Full Text Available Mahkota dewa plant (Phaleria macrocarpa (Scheff. Boerl. which is belong to family of Thymelaeaceae is one of Indonesia's traditional medicines. The aim of this research is to isolate secondary metabolites from ethyl acetate extract of leave and fruit of mahkota dewa and to determine the molecular structure of isolated compounds using spectroscopic method and to know the antibacterial activity of the isolated compound. Sample was extracted with methanol, concentrated then extracted by n-hexane, chloroform and ethyl acetate. The compounds were separated and purified with column chromatography. The compound 1 was isolated from ethyl acetate extract of leave as white needle amorphous solid as 45 mg. The compound was identified by spectroscopic as 4,6-dihydroxy-4’-methoxybenzophenon-2-O-β-D-glucopyranoside and named isophalerin B. From the test results of antibacterial activity showed that the compound 1 (10 mg/mL in ethanol has a weak activity against the bacteria S. aureus and E. coli. The compound 2 was isolated from ethyl acetate extract of fruit as peach needle crystal as 10 mg. The compound was identified by spectroscopic as 4,6-dihydroxy-4’-methoxybenzophenon-2-O-α-D-glucopyranoside and named isophalerin A.

  6. Utilization of ethyl cellulose polymer and waste materials for roofing tile production

    Science.gov (United States)

    Sam, Suubitaa Spencer; Ng, ChoonAun; Chee, Swee Yong; Habib, NoorZainab; Nadeem, Humayon; Teoh, Wei Ping

    2017-05-01

    The aim of this study was to utilize ethyl cellulose, mixture of waste engine oil and waste vegetable oil as a binder in the environmental friendly roofing tile production. The waste engine-vegetable oil wasmix together with ethyl cellulose, fly ash, coarse aggregates, fine aggregatesand a catalyst. The Fourier Transform Infrared (FTIR) analysis showed that the oil mixture added with ethyl cellulose has the relatively high binding effect due to the presence of strong carbonyl group especially after being heat cured at 1900C for 24 hours. The mixed proportion of materials with different amount of ethyl cellulose used was studied in the production of tile specimen. The results showed that the ethyl cellulose composed roofing tile specimens passed the transverse breaking strength, durability, permeabilityand the ultraviolet accelerated test. The shrinkage on the tile can be overcome by adding temperature resistance polymer on the exterior of the tile.

  7. Fungal degradation of an acetolactate synthase (ALS) inhibitor pyrazosulfuron-ethyl in soil.

    Science.gov (United States)

    Sondhia, Shobha; Waseem, Uzma; Varma, R K

    2013-11-01

    Owing to reported phytotoxicity of some sulfonylurea class of herbicides in number of sensitive crops and higher persistence in soil, present study was conducted to isolate and identify pyrazosulfuron-ethyl degrading fungi from soil of rice field. Penicillium chrysogenum and Aspergillus niger, were isolated and identified from rhizospere soil of rice field, as potent pyrazosulfuron-ethyl degrading fungi. Degradation of pyrazosulfuron-ethyl by P. chrysogenum and A. niger, yielded transformation products/metabolites which were identified and characterized by LC/MS/MS. The rate of dissipation of pyrazosulfuron-ethyl was found higher in soil of rice field and soil inoculated with P. chrysogenum. This showed important route of degradation of pyrazosulfuron-ethyl by microbes apart from chemical degradation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Activity coefficients at infinite dilution measurements for organic solutes and water in the ionic liquid 1-ethyl-3-methylimidazolium trifluoroacetate.

    Science.gov (United States)

    Domańska, Urszula; Marciniak, Andrzej

    2007-10-18

    The activity coefficients at infinite dilution, gamma13(infinity) for 29 solutes, alkanes, alkenes, alkynes, cycloalkanes, aromatic hydrocarbons, alcohols and water in the ionic liquid 1-ethyl-3-methylimidazolium trifluoroacetate ([EMIM][TFA]), were determined by gas-liquid chromatography at temperatures from 298.15-368.15 K. The partial molar excess enthalpies at infinite dilution DeltaH1(E,infinity) values were calculated from the experimental gamma13(infinity) values obtained over the temperature range. The selectivities for the hexane/benzene and cyclohexane/benzene separation were calculated from gamma13(infinity) and compared to the literature values for other ionic liquids, NMP and sulfolane.

  9. Understanding the hydrolysis mechanism of ethyl acetate catalyzed by an aqueous molybdocene: a computational chemistry investigation.

    Science.gov (United States)

    Tílvez, Elkin; Cárdenas-Jirón, Gloria I; Menéndez, María I; López, Ramón

    2015-02-16

    A thoroughly mechanistic investigation on the [Cp2Mo(OH)(OH2)](+)-catalyzed hydrolysis of ethyl acetate has been performed using density functional theory methodology together with continuum and discrete-continuum solvation models. The use of explicit water molecules in the PCM-B3LYP/aug-cc-pVTZ (aug-cc-pVTZ-PP for Mo)//PCM-B3LYP/aug-cc-pVDZ (aug-cc-pVDZ-PP for Mo) computations is crucial to show that the intramolecular hydroxo ligand attack is the preferred mechanism in agreement with experimental suggestions. Besides, the most stable intermediate located along this mechanism is analogous to that experimentally reported for the norbornenyl acetate hydrolysis catalyzed by molybdocenes. The three most relevant steps are the formation and cleavage of the tetrahedral intermediate immediately formed after the hydroxo ligand attack and the acetic acid formation, with the second one being the rate-determining step with a Gibbs energy barrier of 36.7 kcal/mol. Among several functionals checked, B3LYP-D3 and M06 give the best agreement with experiment as the rate-determining Gibbs energy barrier obtained only differs 0.2 and 0.7 kcal/mol, respectively, from that derived from the experimental kinetic constant measured at 296.15 K. In both cases, the acetic acid elimination becomes now the rate-determining step of the overall process as it is 0.4 kcal/mol less stable than the tetrahedral intermediate cleavage. Apart from clarifying the identity of the cyclic intermediate and discarding the tetrahedral intermediate formation as the rate-determining step for the mechanism of the acetyl acetate hydrolysis catalyzed by molybdocenes, the small difference in the Gibbs energy barrier found between the acetic acid formation and the tetrahedral intermediate cleavage also uncovers that the rate-determining step could change when studying the reactivity of carboxylic esters other than ethyl acetate substrate specific toward molybdocenes or other transition metal complexes. Therefore

  10. 9-Hydroxyfurodysinin-O-ethyl Lactone: A New Sesquiterpene Isolated from the Tropical Marine Sponge Dysidea arenaria

    Directory of Open Access Journals (Sweden)

    P. Karuso

    2005-10-01

    Full Text Available A new sesquiterpene, 9-hydroxyfurodysinin-O-ethyl lactone, has been isolated from a New Caledonian Dysidea arenaria, along with three known compounds. The possible incorporation of the ethyl ether from the extraction solvent is discussed.

  11. Deconjugation of N-glucuronide conjugated metabolites with hydrazine hydrate - Biomarkers for exposure to the food-borne carcinogen 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)

    DEFF Research Database (Denmark)

    Frandsen, Henrik Lauritz

    2007-01-01

    of PhIP metabolites were unsusceptible to treatment with beta-glucuronidase indicating that these are N-glucuronides. Treatment of the conjugates with hydrazine hydrate, however, resulted in complete hydrolysis of the glucuronic acid conjugates as well as in reduction to the parent amine of metabolites...

  12. Elucidation of the metabolites of the novel psychoactive substance 4-methyl-N-ethyl-cathinone (4-MEC) in human urine and pooled liver microsomes by GC-MS and LC-HR-MS/MS techniques and of its detectability by GC-MS or LC-MS(n) standard screening approaches.

    Science.gov (United States)

    Helfer, Andreas G; Turcant, Alain; Boels, David; Ferec, Séverine; Lelièvre, Bénédicte; Welter, Jessica; Meyer, Markus R; Maurer, Hans H

    2015-05-01

    4-methyl-N-ethcathinone (4-MEC), the N-ethyl homologue of mephedrone, is a novel psychoactive substance of the beta-keto amphetamine (cathinone) group. The aim of the present work was to study the phase I and phase II metabolism of 4-MEC in human urine as well as in pooled human liver microsome (pHLM) incubations. The urine samples were worked up with and without enzymatic cleavage, the pHLM incubations by simple deproteinization. The metabolites were separated and identified by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-high resolution-tandem mass spectrometry (LC-HR-MS/MS). Based on the metabolites identified in urine and/or pHLM, the following metabolic pathways could be proposed: reduction of the keto group, N-deethylation, hydroxylation of the 4-methyl group followed by further oxidation to the corresponding 4-carboxy metabolite, and combinations of these steps. Glucuronidation could only be observed for the hydroxy metabolite. These pathways were similar to those described for the N-methyl homologue mephedrone and other related drugs. In pHLM, all phase I metabolites with the exception of the N-deethyl-dihydro isomers and the 4-carboxy-dihydro metabolite could be confirmed. Glucuronides could not be formed under the applied conditions. Although the taken dose was not clear, an intake of 4-MEC should be detectable in urine by the GC-MS and LC-MS(n) standard urine screening approaches at least after overdose. Copyright © 2014 John Wiley & Sons, Ltd.

  13. Estimation of alcohol consumption during "Fallas" festivity in the wastewater of Valencia city (Spain) using ethyl sulfate as a biomarker.

    Science.gov (United States)

    Andrés-Costa, María Jesús; Escrivá, Úrsula; Andreu, Vicente; Picó, Yolanda

    2016-01-15

    Alcohol consumption has been increasing in the last years and it has become a sociological problem due its derived health and safety problems. Ethyl sulfate is a secondary metabolite of the alcohol degradation that is excreted through the urine (0.010-0.016%) after alcohol ingestion and it is quite stable in water. In this study, a new methodology to determine ethyl sulfate by ion-pair liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. Different ion-pairs and additives were tested directly in the sample extracts or in the mobile phase. The best ion-pair was set up adding 0.5M of tributylamine and 0.1% of formic acid to the sample. The limit of quantification was 0.3 μg L(-1) and the intra-day and inter-day precision of the method were ≤ 2.8 and ≤ 3.0%, respectively. Good linearity (r(2)alcohol consumption ranged from 1.07 to 56.11 mL day(-1) inhab(-1), being the highest value of alcohol consumption determined during Fallas. This study presents a reliable and alternative method to traditional ones to determine alcohol consumption by population that provides real-time information of alcohol consumption. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Antidiabetic activity of the ethyl acetate fraction of Ficus lutea (Moraceae) leaf extract: comparison of an in vitro assay with an in vivo obese mouse model.

    Science.gov (United States)

    Olaokun, Oyinlola O; McGaw, Lyndy J; Janse van Rensburg, Ilse; Eloff, Jacobus N; Naidoo, Vinny

    2016-03-31

    Ficus lutea crude acetone leaf extracts were previously shown to stimulate glucose uptake and insulin secretion of established cells and, inhibit α-amylase and α-glucosidase activities. For this study, F. lutea acetone extracts were subjected to solvent-solvent fractionation to yield fractions with differing polarities (hexane, chloroform, dichloromethane, ethyl acetate, n-butanol and water) in an attempt to obtain a more potent fraction with in vitro and probably in vivo activity. Among these fractions, the ethyl acetate fraction had the highest total polyphenol content (100.5 ± 1.6 mg GAE/g dried extract) and α-glucosidase inhibitory activity (126.8 ± 30.6 μg/ml). It also stimulated the highest glucose uptake of C2C12 muscle cells and decreased extracellular glucose concentration of H-4-II-E liver cells with low cytotoxic activity. The ethyl acetate fraction (10.88 ± 0.55 μg/L at 250 μg/ml) enhanced insulin secretion in RIN-m5F pancreatic β-cells to the same degree as the positive control glibenclamide (11.09 ± 0.07 μg/L at 1μM). While fractionation increased α-glucosidase inhibition and glucose uptake of cells, in the ethyl acetate fraction, the α-amylase inhibition and insulin secretion decreased. The weight reducing and glucose control potential of the ethyl acetate fraction in an obese mouse model, important factors in the amelioration of type II diabetes was determined. The extract had no statistical significant weight reducing activity. A major finding was the decrease in the area under the curve of the glucose concentration over time in animals that were treated with both a change in diet and with the plant extract. This is linked to increased glucose uptake within the cells, the most likely mechanism is either an increased insulin response or increased insulin secretion.

  15. Diffusion of 1-ethyl-3-methyl-imidazolium acetate in glucose, cellobiose, and cellulose solutions.

    Science.gov (United States)

    Ries, Michael E; Radhi, Asanah; Keating, Alice S; Parker, Owen; Budtova, Tatiana

    2014-02-10

    Solutions of glucose, cellobiose and microcrystalline cellulose in the ionic liquid 1-ethyl-3-methyl-imidazolium ([C2mim][OAc]) have been examined using pulsed-field gradient (1)H NMR. Diffusion coefficients of the cation and anion across the temperature range 20-70 °C have been determined for a range of concentrations (0-15% w/w) of each carbohydrate in [C2mim][OAc]. These systems behave as an "ideal mixture" of free ions and ions that are associated with the carbohydrate molecules. The molar ratio of carbohydrate OH groups to ionic liquid molecules, α, is the key parameter in determining the diffusion coefficients of the ions. Master curves for the diffusion coefficients of cation, anion and their activation energies are generated upon which all our data collapses when plotted against α. Diffusion coefficients are found to follow an Arrhenius type behavior and the difference in translational activation energy between free and associated ions is determined to be 9.3 ± 0.9 kJ/mol.

  16. Crystal structures of ethyl 6-(4-methylphenyl-4-oxo-4H-chromene-2-carboxylate and ethyl 6-(4-fluorophenyl-4-oxo-4H-chromene-2-carboxylate

    Directory of Open Access Journals (Sweden)

    Ligia R. Gomes

    2016-01-01

    Full Text Available The crystal structures of two chromone derivatives, viz. ethyl 6-(4-methylphenyl-4-oxo-4H-chromene-2-carboxylate, C19H16O4, (1, and ethyl 6-(4-fluorophenyl-4-oxo-4H-chromene-2-carboxylate C18H13FO4, (2, have been determined: (1 crystallizes with two molecules in the asymmetric unit. A comparison of the dihedral angles beween the mean planes of the central chromone core with those of the substituents, an ethyl ester moiety at the 2-position and a para-substituted phenyl ring at the 6-position shows that each molecule differs significantly from the others, even the two independent molecules (a and b of (1. In all three molecules, the carbonyl groups of the chromone and the carboxylate are trans-related. The supramolecular structure of (1 involves only weak C—H...π interactions between H atoms of the substituent phenyl group and the phenyl group, which link molecules into a chain of alternating molecules a and b, and weak π–π stacking interactions between the chromone units. The packing in (2 involves C—H...O interactions, which form a network of two intersecting ladders involving the carbonyl atom of the carboxylate group as the acceptor for H atoms at the 7-position of the chromone ring and from an ortho-H atom of the exocyclic benzene ring. The carbonyl atom of the chromone acts as an acceptor from a meta-H atom of the exocyclic benzene ring. π–π interactions stack the molecules by unit translation along the a axis.

  17. Influence of UGT1A9 intronic I399C>T polymorphism on SN-38 glucuronidation in Asian cancer patients.

    Science.gov (United States)

    Sandanaraj, E; Jada, S R; Shu, X; Lim, R; Lee, S C; Zhou, Q; Zhou, S; Goh, B C; Chowbay, B

    2008-06-01

    Genetic polymorphisms in hepatically expressed UGT1A1 and UGT1A9 contribute to the interindividual variability i-n irinotecan disposition and toxicity. We screened UGT1A1 (UGT1A1*60, g.-3140G>A, UGT1A1*28 and UGT1A1*6) and UGT1A9 (g.-118(T)(9>10) and I399C>T) genes for polymorphic variants in the promoter and coding regions, and the genotypic effect of UGT1A9 I399C>T polymorphism on irinotecan disposition in Asian cancer patients was investigated. Blood samples were collected from 45 patients after administration of irinotecan as a 90 min intravenous infusion of 375 mg/m(2) once in every 3 weeks. Genotypic-phenotypic correlates showed that cancer patients heterozygous or homozygous for the I399C>T allele had approximately 2-fold lower systemic exposure to SN-38 (P0.05). UGT1A1-1A9 diplotype analysis showed that patients harbouring the H1/H2 (TG6GT(10)T/GG6GT(9)C) diplotype had 2.4-fold lower systemic exposure to SN-38 glucuronide (SN-38G) compared with patients harbouring the H1/H5 (TG6GT(10)T/GG6GT(10)C) diplotype (P=0.025). In conclusion, this in vivo study supports the in vitro findings of Girard et al. and suggests that the UGT1A9 I399C>T variant may be an important glucuronidating allele affecting the pharmacokinetics of SN-38 and SN-38G in Asian cancer patients receiving irinotecan chemotherapy.

  18. Rates of nitrogen and growth retardant trinexapac-ethyl on wheat.

    OpenAIRE

    ESPINDULA, M. C.; ROCHA, V. S.; SOUZA, L. T. de.; SOUZA, M. A. de.; CAMPANHARO, M.; GROSSI, J. A. S.

    2011-01-01

    The objective in this study was to evaluate the effects of nitrogen rates in association with rates of the growth retardant trinexapac-ethyl on wheat. The experiment was conducted in Viçosa, MG and arranged in a 5×4 factorial, randomized block design, with four repetitions. A combination of five nitrogen rates (30, 60, 90, 120 and 150kg ha-1) with four rates of trinexapac-ethyl (0, 62.5, 125 and 187.5g ha-1) were tested. Trinexapac-ethyl promotes reduction of soot dry mass and grain yie...

  19. Ethyl cellulose nanoparticles: clarithomycin encapsulation and eradication of H. pylori.

    Science.gov (United States)

    Pan-In, Porntip; Banlunara, Wijit; Chaichanawongsaroj, Nuntaree; Wanichwecharungruang, Supason

    2014-08-30

    The extreme acidic environment of the stomach, its regular voidance of contents and the restricted access to the mucus covered habitat combined with the antibiotic resistance of the bacteria, all contribute to the poor success in the treatment of Helicobacter pylori gastric infections. Here, we demonstrate that by encapsulating clarithromycin into ethyl cellulose (EC) nanoparticles, the efficiency of H. pylori clearance in C57BL/6 mice infected with these bacteria was significantly improved. Clarithomycin-loaded EC nanoparticles were prepared via a simple yet effective anti-solvent particle induction method, to yield sub-micron sized particles with 22.3 ± 0.17% (w/w) clarithromycin loading at 86 ± 0.5% (w/w) encapsulation efficiency. The particles dispersed well in water and simulated gastric fluid and gave a minimum inhibitory concentration of 0.09-0.18 μg/ml against four strains of H. pylori. Encapsulation into EC particles not only enhanced the anti-adhesion activity of clarithromycin when tested with H. pylori and Hep-2 cells, but also gave significant enhancement of H. pylori clearance in the stomach of C57BL/6 mice infected with the bacteria. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Membrane Separation of 2-Ethyl Hexyl Amine/1-Decene

    KAUST Repository

    Bawareth, Bander

    2012-12-01

    1-Decene is a valuable product in linear alpha olefins plants that is contaminated with 2-EHA (2-ethyl hexyl amine). Using organic solvent nanofiltration membranes for this separation is quite challengeable. A membrane has to be a chemically stable in this environment with reasonable and stable separation factor. This paper shows that Teflon AF 2400 and cellulose acetate produced interesting results in 1-decene/2-EHA separation. The separation factor of Teflon AF 2400 is 3 with a stable permeance of 1.1x10-2 L/(m2·h·bar). Likewise, cellulose acetate gave 2-EHA/1-decene separation factor of 2 with a lower permeance of 3.67x10-3 L/(m2·h·bar). A series of hydrophilic membranes were tested but they did not give any separation due to high degree of swelling of 2-EHA with these polymers. The large swelling causes the membrane to lose its diffusivity selectivity because of an increase in the polymer\\'s chain mobility.

  1. Ocular surface frostbite secondary to ethyl chloride spray.

    Science.gov (United States)

    Rodriguez, Nelson A; Ascaso, Francisco J

    2012-03-01

    Ethyl chloride (EC) is a fast-acting vapo-coolant spray that provides rapid, transient, local analgesia for minor invasive procedures. Although the application of EC has decreased, it can be used as a cryoanalgesic agent in minor surgical procedures. Despite the widespread use of EC as a local anesthetic, there are few reported cases of serious adverse side effects. We report a 67-year old otherwise healthy man who underwent excision of a papilloma on his superior right eyelid by a general practitioner at a primary care center. The lesion was removed by curettage after slight freezing with EC spray. This chemical agent was applied without the adequate eye protection, and eight hours later the patient presented an acute frost injury of ocular surface. Urgent treatment included copious irrigation of the affected eye, especially the conjunctival fornices, corticosteroid (prednisone) and antibiotic (neomycin) ointment. A week later, the eyelid lesion and keratoconjunctivitis had resolved but evidence of early cicatrization involving the inferior conjucntival fornix and symblepharon formation were present. To the best of our knowledge, this is the first reported case of an acute burn of the ocular surface following EC spray exposure. EC should be avoided for short-term local anesthesia in the periocular region to prevent this serious complication.

  2. Determinação de metil-etil-cetona em amostras de urina com amostragem por micro extração em fase sólida (MEFS em headspace associada à cromatografia gasosa com detector de ionização de chama (CG-DIC Determination of methyl ethyl ketone in urine samples by headspace solid phase micro extraction (SPME sampling associated to gas chromatography with flame-ionization detectoR (GC-FID

    Directory of Open Access Journals (Sweden)

    Marina Venzon Antunes

    2008-01-01

    Full Text Available Methyl ethyl ketone (MEK is a solvent commonly used in chemical, paint and shoe industry. The aim of this study was to develop and validate a method for urinary quantification of MEK, employing headspace solid phase micro extraction sampling (SPME coupled to gas chromatography with flame ionization detection (GC-FID. The calibration curve (y=4.6851x-0.0011 presented good linearity with r²=0.9993. Accuracy (94-109%, intra-assay precision (4.07-5.91% and inter-assay precision (3.03-5.62% were acceptable. The quantification limit was 0.19 mg/L. This low cost method can be used routinely in the biological monitoring of occupational exposure to MEK, according to the requirements of the Brazilian legislation.

  3. Caracteres morfoanatômicos de Brachiaria brizantha submetida à aplicação de Trinexapac-Ethyl Anatomical characters of Brachiaria brizantha submitted to Trinexapac-Ethyl application

    Directory of Open Access Journals (Sweden)

    C.M.T. Fialho

    2009-01-01

    application, samples from the middle third of the sheath, blade of the second fully expanded leaf and stem internode below the leaf sheath insertion were collected for the determination of morphological characteristics, such as plant height, internode length and diameter, sheath length and leaf length and width. For evaluation of the anatomical features, transverse cuts of leaves, stem and sheath and longitudinal cuts of the stem were made, in table microtome and stained with fuchsin and astra blue and prepared into semi-permanent slides. The images obtained were scanned using a light microscope coupled to a digital camera and connected to a computer. To obtain area and linear measures, the software Image Pro-Plus was used. The data were subjected to statistical analysis, using the F test at 10% probability. The growth regulator reduced the length of tho the leaf blade, internode and sheath and also plant height. On the other hand, trinexapac-ethyl increased leaf blade thickness sheath cell and mesophyll areas, providing anatomical and morphological changes in B. brizantha.

  4. New Look at odorization levels for propane gas. [Ethyl mercaptan; thiophane; equilibrium K values

    Energy Technology Data Exchange (ETDEWEB)

    Whisman, M.L.; Goetzinger, J.W.; Cotton, F.O.; Brinkman, D.W.; Thompson, C.J.

    1977-09-01

    Nearly 4,000 persons participated in a study to evaluate three odorant systems in four test modes and at 24 different test sites. Participants included trained panels, untrained ERDA employees, and several thousand untrained volunteer evaluators. The classical testing technique and three modified test modes were used to represent a spectrum of conditions that would define the effect of environmental familiarity and mental distractions upon olfactory responses to LP-gas. Significant efforts were directed toward determination of odorant levels that not only can be detected but also will be detected. The study showed that in addition to defects of the nasal anatomy, psychological factors also affect olfactory responses, and that unfamiliarity with a given environment as well as anxieties or mental distractions can produce reduced awareness to odorants intended to warn individuals of the presence of LP-gas. A second part of the study involved a laboratory determination of equilibrium K-values for both ethyl mercaptan and thiophane at three temperatures. Novel sample handling and gas chromatographic techniques provided reproducible results which were in close agreement with theoretical predictions. (28 tables, 29 tables)

  5. Rotational Spectroscopy of Two Tellurol Compounds : Ethyl and Vinyl-Tellurol

    Science.gov (United States)

    Motiyenko, R.; Margulès, L.; Goubet, M.; Møllendal, H.; Guillemin, J. C.

    2009-06-01

    Among the compounds containing a chalcogen, the tellurols (R-TeH) have been poorly investigated previously. Only H_2Te was studied in rotational spectroscopy. This fact can be explained by high toxicity and high chemical reactivity of these compounds. However quite recently, a new method allowing easily obtention of pure samples has been reported. Thanks to this approach, very high acidity of these tellurols in gas phase has been measured and photoelectron spectra have been recorded. It should be noted that, even if simple derivatives are known since a long time, no microwave spectrum of these compounds has been recorded previously. The determination of their rotational constants is however a determining step to have a quite complete knowledge of such systems and to be able to perform comparisons of their physicochemical properties with those of the corresponding thiols and selenols which have been more extensively studied. The rotational spectra of vinyl and ethyl-tellurol have been recorded in the frequency range up to 210 GHz. For both compounds gauche forms have been assigned due to rather distinguishable patterns of a-type transitions. The assignments were confirmed by comparison with the results of ab initio calculations. For ethyl-tellurol the rotational transitions were observed as doublets. The splittings are probably caused by tunneling effect between two equivalent configurations (gauche^+, gauche^-). The assignment and analysis of the rotational spectra of both molecules is in progress. The latest results will be reported. I. N. Kozin, P. Jensen, O. Polanz, S. Klee, L. Poteau, and J. Demaison, J. Mol. Spectrosc., 180 402-413 (1996) J. C. Guillemin, A. Bouayard, D. Vijaykumar, D. Chem. Commun., 1163-1164 (2000) J. C. Guillemin, El. H. Riague, J. F. Gal, P. C. Marris, O. Mo., M. Yanez, Chem. Eur. J. 11, 2145-2153 (2005) B. Khater, J. C. Guillemin, G. Bajor, T. Veszprémi, P. C. Marris, O. Mo., M. Yanez, Inorg. Chem. 112, 3053-3060 (2008) A. Baroni, Atti

  6. Icosapent ethyl (eicosapentaenoic acid ethyl ester): Effects on plasma apolipoprotein C-III levels in patients from the MARINE and ANCHOR studies.

    Science.gov (United States)

    Ballantyne, Christie M; Bays, Harold E; Braeckman, Rene A; Philip, Sephy; Stirtan, William G; Doyle, Ralph T; Soni, Paresh N; Juliano, Rebecca A

    2016-01-01

    Apolipoprotein C-III (ApoC-III) regulates lipoprotein and triglyceride (TG) metabolism and may have a causal role in cardiovascular disease. In the Multi-Center, Placebo-Controlled, Randomized, Double-Blind, 12-Week Study With an Open-Label Extension (MARINE) and ANCHOR studies, icosapent ethyl, a high-purity prescription eicosapentaenoic acid ethyl ester, reduced TG, and other atherogenic lipid parameters without increasing low-density lipoprotein cholesterol (LDL-C) compared with placebo. To evaluate the effects of icosapent ethyl on plasma ApoC-III levels in patients from 2 phase 3 studies. MARINE and ANCHOR were 12-week double-blind studies of icosapent ethyl in adult patients. Patients in MARINE had very high TG levels (≥500 and ≤2000 mg/dL) and patients in ANCHOR had high TG levels (≥200 and ANCHOR assessed the median percent change from baseline in plasma ApoC-III levels vs placebo and includes subgroup analyses by statin use/efficacy and median ApoC-III levels. We assessed ApoC-III levels in 148 and 612 patients in the MARINE and ANCHOR studies, respectively. In MARINE, the approved prescription dose of icosapent ethyl (4 g/day) significantly reduced ApoC-III levels by 25.1% (P ANCHOR, icosapent ethyl 4 g/day significantly reduced ApoC-III levels by 19.2% (P ANCHOR studies. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  7. Isolation and Characterization Compounds From Hexane and Ethyl Acetate Fractions of Peperomia pellucida L.

    Directory of Open Access Journals (Sweden)

    Sri Hartati

    2015-09-01

    Full Text Available Peperomia pellucida was used traditionally in Indonesia for health treatment: wounds, boils, pimples, abscesses, abdominal pain, colic, gout, kidney, rheumatic pain, fatigue headache, furuncles, conjunctivitis and anti dermatogenic and also for dengue treatment. The isolation compounds from hexane and ethyl acetate fractions of Peperomia pellucida L. are conducted by maceration of the dry herbs sample with methanol and partition with hexane, ethyl acetate, butanol and water. The hexane and ethyl acetate fractions were fractionated by gravitation column chromatography and eluted successively with hexane, ethyl acetate and methanol by the gradient. The structure was elucidated base on spectroscopy data of NMR proton and carbon for one and two dimension, LCMS and FT-IR. The isolation founded three compounds are stigmasterol, analogue of pheophytin and β-sitosterol-D-glucopyranoside.

  8. Biofiltration of ethyl acetate by Pseudomonas putida immobilized on walnut shell.

    Science.gov (United States)

    Zare, Hossein; Najafpour, Ghasem; Rahimnejad, Mostafa; Tardast, Ali; Gilani, Saeedeh

    2012-11-01

    A biofilter packed with walnut shells was used to eliminate ethyl acetate from an air stream. The shells treated with NaOH were used as medium for immobilization of Pseudomonas putida PTCC 1694. At an empty bed residence time (EBRT) of 60s, a removal efficiency of 99% was achieved at inlet concentrations lower than 430ppm of ethyl acetate. The removal efficiency decreased below 80% with an increase in inlet concentration of ethyl acetate. When the EBRT was increased to 75 s, the removal efficiency remained above 80% even though the inlet loading rate was increased to 421g/m(3)h. Michaelis-Menten type and zero-order diffusion limited models were employed and the predicted data perfectly matched the experimental data. Thus P. putida immobilized on walnut shell has potential for the removal of ethyl acetate from air streams. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Inhibition of Pro-inflammatory Cytokines by Ethyl Acetate Extract of ...

    African Journals Online (AJOL)

    inflammatory production by macrophages. Methods: Mouse peritoneal macrophages were cultured in solvent either alone or with 2 ìg/ml lipopolysaccaride (LPS) with/without different doses of ethyl acetate extract of S. striata. Production of ...

  10. Hydrogen Production via Steam Reforming of Ethyl Alcohol over Palladium/Indium Oxide Catalyst

    Directory of Open Access Journals (Sweden)

    Tetsuo Umegaki

    2009-01-01

    Full Text Available We report the synergetic effect between palladium and indium oxide on hydrogen production in the steam reforming reaction of ethyl alcohol. The palladium/indium oxide catalyst shows higher hydrogen production rate than indium oxide and palladium. Palladium/indium oxide affords ketonization of ethyl alcohol with negligible by-product carbon monoxide, while indium oxide mainly affords dehydration of ethyl alcohol, and palladium affords decomposition of ethyl alcohol with large amount of by-product carbon monoxide. The catalytic feature of palladium/indium oxide can be ascribed to the formation of palladium-indium intermetallic component during the reaction as confirmed by X-ray diffraction and X-ray photoelectron spectroscopic measurements.

  11. α-Glucosidase Inhibitory Activity from Ethyl Acetate Extract ofAntidesma bunius(L.) Spreng Stem Bark Containing Triterpenoids.

    Science.gov (United States)

    Mauldina, Marista Gilang; Sauriasari, Rani; Elya, Berna

    2017-01-01

    Buni ( Antidesma bunius [L.] Spreng) has been used as a traditional antidiabetic agent in Asia. The mechanism of antidiabetic properties was studied in this study by determine its α-glucosidase inhibitory activity. Inhibition of α-glucosidase was performed in all fraction of Buni stem bark with acarbose and miglitol as standards. The half maximal inhibitory concentration (IC 50 ) value of acarbose and miglitol was 5.75 and 59.76 μg/mL respectively while ethyl acetate (EtOAc) fraction was the most active fraction with IC 50 of 19.33 μg/mL. Three isolates (B1, B2, and B3) were found in the EtOAc fraction and elucidated by infrared, 1 hydrogen-nuclear magnetic resonance, 13 carbon-nuclear magnetic resonance, and two-dimensional nuclear magnetic resonance. The chemical structures of the isolates were identified by the spectrum then compared with literature which concluded that B1 is friedelin, B2 is β-sitosterol, and B3 is betulinic acid. Inhibition of the α-glucosidase assay showed IC 50 values of B1, B2, and B3 were 19.51, 49.85, and 18.49 μg/mL, respectively. α-Glucosidase inhibitory activity assay was performed in n-hexane, ethyl acetate (EtOAc), methanol fraction of Buni ( Antidesma bunius (L.) Spreng) stem bark and miglitolEtOAc fraction from the liquid chromatography has the highest inhibitory activity against α-glucosidaseThe chemical structures of the isolates were identified by the spectrums infrared, 1 hydrogen-nuclear magnetic resonance, 13 carbon-nuclear magnetic resonance, and two-dimensional nuclear magnetic resonance, then compared with literature which concluded that B1 is friedelin, B2 is β-sitosterol, and B3 is betulinic acidBetulinic acid and friedelin showed the highest α-glucosidase inhibitory activity. Abbreviations used: IC 50 : Half maximal inhibitory concentration; H-NMR: Hydrogen-nuclear magnetic resonance; C-NMR: Carbon nuclear magnetic resonance; 2D-NMR: Two dimensional-nuclear magnetic resonance; EtOH: Ethanol; EtOAc: Ethyl

  12. Behavior of ethyl linoleate in batch rectification of aqueous ethanol solution containing linoleic acid; Rinoru san wo fukumu etanoru suiyoeki no kaibun jyoryu ni okeru rinoru san echiru no ryoshutsu kyodo

    Energy Technology Data Exchange (ETDEWEB)

    Kashiwada, Masanori; Kawano, Yoshinobu; Shiomori, Koichiro [Miyazai University, Miyazaki (Japan). Department of Materials Science; Aiko, Ryoko; Uemura, Yoshimitsu; Hatate, Yasuo [Kagoshima University, Kagoshima (Japan). Department of Applied Chemistry and Chemical Engineering

    1999-03-10

    In shochu mash containing citric acid, fatty acids react with ethyl alcohol to form their esters having high volatility, and the taste and smell of shochu are influenced by these esters. Ester formation rates between ethanol and linoleic acid were measured at various temperatures. The formation rates are affected by the concentrations of linoleic acid, citric acid as catalyst, and ethanol, and by the reaction temperature. The rate equation of esterification of the linoleic acid is formulated as a function of the concentrations of linoleic acids (C{sub L}), citric acid (C{sub C}) and ethyl alcohol (C{sub E}) as follows. r=k{sub L} C{sub L}{sup l} C{sub C}{sup m} C{sub E}{sup n} The exponents l, m and n were determined. Furthermore, the rate constant (K{sub L}) was estimated as a function of temperature. The distillation behavior of aqueous ethanol solution containing linoleic acid is measured. No linoleic acid is detected in the distillation effluent. The distillation behavior of ethyl linoleate is interpreted based on the esterification of linoleic acid by ethyl alcohol in the distillation still and the equilibrium of ethyl linoleate in aqueous ethanol solution. (author)

  13. Catalyst-free ethyl biodiesel production from rice bran under subcritical condition

    Science.gov (United States)

    Zullaikah, Siti; Afifudin, Riza; Amalia, Rizky

    2015-12-01

    In-situ ethyl biodiesel production from rice bran under subcritical water and ethanol with no catalyst was employed. This process is environmentally friendly and is very flexible in term of feedstock utilization since it can handle relatively high moisture and free fatty acids (FFAs) contents. In addition, the alcohol, i.e. bioethanol, is a non-toxic, biodegradable, and green raw material when produced from non-edible biomass residues, leading to a 100% renewable biodiesel. The fatty acid ethyl esters (FAEEs, ethyl biodiesel) are better than fatty acid methyl esters (FAMEs, methyl biodiesel) in terms of fuel properties, including cetane number, oxidation stability and cold flow properties. The influences of the operating variables such as reaction time (1 - 10 h), ethanol concentration (12.5 - 87.5%), and pressurizing gas (N2 and CO2) on the ethyl biodiesel yield and purity have been investigated systematically while the temperature and pressure were kept constant at 200 °C and 40 bar. The optimum results were obtained at 5 h reaction time and 75% ethanol concentration using CO2 as compressing gas. Ethyl biodiesel yield and purity of 58.78% and 61.35%, respectively, were obtained using rice bran with initial FFAs content of 37.64%. FFAs level was reduced to 14.22% with crude ethyl biodiesel recovery of 95.98%. Increasing the reaction time up to 10 h only increased the yield and purity by only about 3%. Under N2 atmosphere and at the same operating conditions (5h and 75% ethanol), ethyl biodiesel yield and purity decreased to 54.63% and 58.07%, respectively, while FFAs level was increased to 17.93% and crude ethyl biodiesel recovery decreased to 87.32%.

  14. Evaluation and Characterization of Biodiesels Obtained Through Ethylic or Methylic Transesterification of Tryacylglicerides in Corn Oil

    OpenAIRE

    Douglas Queiroz Santos; Ana Paula de Lima; Maíra Martins Franco; David Maikel Fernandes; Waldomiro Borges Neto; José Domingos Fabris

    2014-01-01

    This work was devoted to the transesterification of corn oil either with methyl or ethyl alcohol and to the characterization of the biodiesels (composed by FAME—fatty acid methyl esters—or FAEE—fatty acid ethyl esters, respectively) produced. As an initial hypothesis, it was argued whether or not the two alcohols, both with short molecular chains, would impart significant differences to the chemical characteristics of the two biodiesels from corn oil. The most common properties of the biodies...

  15. Trinexapac-Ethyl and Sulfometuron-Methyl Selectivity to Young Eucalyptus Plants

    OpenAIRE

    Correia,N.M.; Villela,G.B.

    2015-01-01

    Trinexapac-ethyl and sulfometuron-methyl are the most widely used ripeners in sugarcane. The application is performed by airborne spraying. Thus, if weather conditions are unfavorable, spray drift to neighboring areas may occur. The objective of this study was to assess the selectivity of the plant growth regulators trinexapac-ethyl and sulfometuron-methyl, used as sugarcane ripeners, to eucalyptus (Eucalyptus urograndis) young plants. The experiment was installed in an eucalyptus commercial ...

  16. Hydrocracking of ethyl laurate on bifunctional micro-/mesoporous composite materials

    Energy Technology Data Exchange (ETDEWEB)

    Adam, M.; Busse, O.; Reschetilowski, W. [Technische Univ. Dresden (Germany). Inst. for Industrial Chemistry

    2011-07-01

    Hydrocracking of ethyl laurate (dodecanoic acid ethyl ester) as a representative model compound of vegetable oil has been investigated in a fixed bed reactor under integral conditions. A synthesized micro-/mesoporous composite support material Al-MCM-41/ZSM-5 modified by different metal loadings (NiMo, NiW, PtNiW) was used as catalyst system. It could be demonstrated that the metal loading and reducibility influence product selectivity as well as deactivation behavior of catalyst samples. (orig.)

  17. Isolation and Characterization Compounds From Hexane and Ethyl Acetate Fractions of Peperomia Pellucida L.

    OpenAIRE

    Hartati, Sri; Angelina, Marissa; Dewiyanti, Indah; Meilawati, Lia

    2015-01-01

    Peperomia pellucida was used traditionally in Indonesia for health treatment: wounds, boils, pimples, abscesses, abdominal pain, colic, gout, kidney, rheumatic pain, fatigue headache, furuncles, conjunctivitis and anti dermatogenic and also for dengue treatment. The isolation compounds from hexane and ethyl acetate fractions of Peperomia pellucida L. are conducted by maceration of the dry herbs sample with methanol and partition with hexane, ethyl acetate, butanol and water.The hexane and et...

  18. Microtropins A-I: 6'-O-(2″S,3″R)-2″-ethyl-2″,3″-dihydroxybutyrates of aliphatic alcohol β-D-glucopyranosides from the branches of Microtropis japonica.

    Science.gov (United States)

    Uemura, Yuka; Sugimoto, Sachiko; Matsunami, Katsuyoshi; Otsuka, Hideaki; Takeda, Yoshio; Kawahata, Masatoshi; Yamaguchi, Kentaro

    2013-03-01

    From the branches of Microtropis japonica (Celastraceae), nine aliphatic glucosides, named microtropins A-I, were isolated. The 6-position of glucose was esterified with (2S,3R)-2-ethyl-2,3-dihydroxybutyric acid. Microtropins A-D contained a rare natured product nitrile functional group in their aglycones. The absolute structures of the (2S,3R)-2-ethyl-2,3-dihydroxybutyric acid moiety and aglycone of microtropin A were determined by an X-ray crystallographic method. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Probabilistic dietary exposure to ethyl carbamate from fermented foods and alcoholic beverages in the Korean population.

    Science.gov (United States)

    Choi, B; Ryu, D; Kim, C-I; Lee, J-Y; Choi, A; Koh, E

    2017-11-01

    The occurrence of ethyl carbamate was investigated in fermented foods and alcoholic beverages of the Korean total diet study. The concentrations of ethyl carbamate ranged from not detected to 166.5 μg kg-1. Dietary exposure to ethyl carbamate was estimated by the probabilistic method. Estimated intakes of ethyl carbamate from foods and alcoholic beverages were 4.12 ng kg-1 body weight (bw) per day for average consumers and 12.37 ng kg-1 bw/day for 95th percentile high consumers. The major foods contributing to ethyl carbamate exposure were soy sauce (63%), followed by maesilju (plum liqueur, 30%), whisky (5%), and bokbunjaju (black raspberry wine, 2%). On the basis of the benchmark dose lower confidence limit 10% (BMDL10) of 0.3 mg kg-1 bw/day, margins of exposure were 128,000 for mean exposure and 40,000 for 95th percentile exposure. This indicates that the exposure of the Korean general population for ethyl carbamate is of low concern. However, careful vigilance should be continued for high consumers of fermented foods and alcoholic beverages.

  20. Simulation of Pressure-swing Distillation for Separation of Ethyl Acetate-Ethanol-Water

    Science.gov (United States)

    Yang, Jing; Zhou, Menglin; Wang, Yujie; Zhang, Xi; Wu, Gang

    2017-12-01

    In the light of the azeotrope of ethyl acetate-ethanol-water, a process of pressure-swing distillation is proposed. The separation process is simulated by Aspen Plus, and the effects of theoretical stage number, reflux ratio and feed stage about the pressure-swing distillation are optimized. Some better process parameters are as follows: for ethyl acetate refining tower, the pressure is 500.0 kPa, theoretical stage number is 16, reflux ratio is 0.6, feed stage is 5; for crude ethanol tower, the pressure is 101.3 kPa, theoretical stage number is 15, reflux ratio is 0.3, feed stage is 4; for ethanol tower, the pressure is 101.3 kPa, theoretical stage number is 25, reflux ratio is 1.2, feed stage is 10. The mass fraction of ethyl acetate in the bottom of the ethyl acetate refining tower reaches 0.9990, the mass fraction of ethanol in the top of the ethanol tower tower reaches 0.9017, the mass fraction of water in the bottom of the ethanol tower tower reaches 0.9622, and there is also no ethyl acetate in the bottom of the ethanol tower. With laboratory tests, experimental results are in good agreement with the simulation results, which indicates that the separation of ethyl acetate ethanol water can be realized by the pressure-swing distillation separation process. Moreover, it has certain practical significance to industrial practice.

  1. Screening of Methanol Extract and Ethyl Acetate Fraction of Abies webbiana Lindl. for Neuropharmacological Activities.

    Science.gov (United States)

    Parkash, O; Kumar, D; Kumar, S

    2015-01-01

    Despite a long traditional of use of Abies webbiana Lindl. (Talispatra; family-Pinaceae) in the treatment of mental disorders, the plant has not been investigated systematically to validate its traditional claims. Thus, the present investigation was undertaken with an objective to investigate neuropharmacological activities of methanol extract of Abies webbiana aerial parts and its ethyl acetate fraction. Properly identified aerial parts were defatted with petroleum ether and then extracted with methanol in a Soxhlet apparatus. Ethyl acetate fraction was prepared by partitioning methanol extract with ethyl acetate using standard procedure. In acute toxicity study, no mortality was observed in animals after oral administration of 2 g/kg dose of methanol extract. The methanol extract (200 or 400 mg/kg, p.o.) and ethyl acetate fraction (25 or 50 mg/kg, p.o.) were evaluated for antianxiety, anticonvulsant, antidepressant, sedative, antistress and analgesic activities using well established models. The methanol extract and ethyl acetate fraction of Abies webbiana aerial parts exhibited significant antianxiety, anticonvulsant, antidepressant, sedative, antistress and analgesic activities with respect to control. Preliminary phytochemical screening showed presence of flavonoids in bioactive ethyl acetate fraction of Abies webbiana aerial parts. It is finally concluded that flavonoids are the bioactive constituents responsible for most of neuropharmacological activities of Abies webbiana.

  2. Formation of ethyl acetate by Kluyveromyces marxianus on whey: studies of the ester stripping.

    Science.gov (United States)

    Urit, Thanet; Löser, Christian; Wunderlich, Martin; Bley, Thomas

    2011-06-01

    Kluyveromyces marxianus is capable of converting lactose into ethyl acetate offering a chance for an economical reuse of whey. The microbial formation of ethyl acetate as a bulk product calls for an aerobic process and, thus, the highly volatile ethyl acetate is discharged from the aerated bioreactor. This stripping process was modeled and investigated experimentally. The stripping rate was proportional to the gas flow and nearly independent of the stirring rate since the stripping was governed by the absorption capacity of the exhaust gas rather than the phase transfer. Cooling the exhaust gas did not noticeably influence the stripping. One batch experiment is presented in detail to demonstrate the formation of ethyl acetate by K. maxianus DSM 5422 on whey. Further batch experiments showed that a substantial formation of ethyl acetate only occurred when the yeast growth was limited by a lack of trace elements. The highest product yield observed was 0.25 g ethyl acetate per g lactose which is nearly 50% of the theoretical maximum.

  3. Decontamination of 2-Chloroethyl Ethyl Sulfide by Pulsed Corona Plasma

    Science.gov (United States)

    Li, Zhanguo; Hu, Zhen; Cao, Peng; Zhao, Hongjie

    2014-11-01

    Decontamination of 2-chloroethyl ethyl sulfide (2-CEES, CH3CH2SCH2CH2Cl) by pulsed corona plasma was investigated. The results show that 212.6 mg/m3 of 2-CEES, with the gas flow rate of 2 m3/h, can be decontaminated to 0.09 mg/m3. According to the variation of the inlet and outlet concentration of 2-CEES vapor with retention time, it is found that the reaction of 2-CEES in a pulsed corona plasma system follows the first order reaction, with the reaction rate constant of 0.463 s-1. The decontamination mechanism is discussed based on an analysis of the dissociation energy of chemical bonds and decontamination products. The C-S bond adjacent to the Cl atom will be destroyed firstly to form CH3CH2S· and ·CH2CH2Cl radicals. CH3CH2S· can be decomposed to ·C2H5 and ·S. ·S can be oxidized to SO2, while ·C2H5 can be finally oxidized to CO2 and H2O. The C-Cl bond in the ·CH2CH2Cl radical can be destroyed to form ·CH2CH2. and ·Cl, which can be mineralized to CO2, H2O and HCl. The H atom in the ·CH2CH2Cl radical can also be substituted by ·Cl to form CHCl2-CHCl2.

  4. ETHYL CYANIDE ON TITAN: SPECTROSCOPIC DETECTION AND MAPPING USING ALMA

    Energy Technology Data Exchange (ETDEWEB)

    Cordiner, M. A.; Palmer, M. Y.; Nixon, C. A.; Charnley, S. B.; Mumma, M. J.; Serigano, J. [NASA Goddard Space Flight Center, 8800 Greenbelt Road, Greenbelt, MD 20771 (United States); Irwin, P. G. J. [Atmospheric, Oceanic and Planetary Physics, Clarendon Laboratory, University of Oxford, Parks Road, Oxford, OX1 3PU (United Kingdom); Teanby, N. A. [School of Earth Sciences, University of Bristol, Wills Memorial Building, Queen’s Road, Bristol, BS8 1RJ (United Kingdom); Kisiel, Z. [Institute of Physics, Polish Academy of Sciences, Al. Lotnikøw 32/46, 02-668 Warszawa (Poland); Kuan, Y.-J.; Chuang, Y.-L. [National Taiwan Normal University, Taipei 116, Taiwan (China); Wang, K.-S., E-mail: martin.cordiner@nasa.gov [Institute of Astronomy and Astrophysics, Academia Sinica, Taipei 106, Taiwan (China)

    2015-02-10

    We report the first spectroscopic detection of ethyl cyanide (C{sub 2}H{sub 5}CN) in Titan’s atmosphere, obtained using spectrally and spatially resolved observations of multiple emission lines with the Atacama Large Millimeter/submillimeter Array (ALMA). The presence of C{sub 2}H{sub 5}CN in Titan’s ionosphere was previously inferred from Cassini ion mass spectrometry measurements of C{sub 2}H{sub 5}CNH{sup +}. Here we report the detection of 27 rotational lines from C{sub 2}H{sub 5}CN (in 19 separate emission features detected at >3σ confidence) in the frequency range 222–241 GHz. Simultaneous detections of multiple emission lines from HC{sub 3}N, CH{sub 3}CN, and CH{sub 3}CCH were also obtained. In contrast to HC{sub 3}N, CH{sub 3}CN, and CH{sub 3}CCH, which peak in Titan’s northern (spring) hemisphere, the emission from C{sub 2}H{sub 5}CN is found to be concentrated in the southern (autumn) hemisphere, suggesting a distinctly different chemistry for this species, consistent with a relatively short chemical lifetime for C{sub 2}H{sub 5}CN. Radiative transfer models show that C{sub 2}H{sub 5}CN is most concentrated at altitudes ≳200 km, suggesting production predominantly in the stratosphere and above. Vertical column densities are found to be in the range (1–5) × 10{sup 14} cm{sup −2}.

  5. Elevated ethyl methanesulfonate (EMS) in nelfinavir mesylate (Viracept, Roche): overview.

    Science.gov (United States)

    Pozniak, Anton; Müller, Lutz; Salgo, Miklos; Jones, Judith K; Larson, Peter; Tweats, David

    2009-08-06

    Roche's protease inhibitor nelfinavir mesylate (Viracept) produced between March 2007-June 2007 was found to contain elevated levels of ethyl methanesulfonate (EMS), a known mutagen (alkylator) - leading to a global recall of the drug. EMS levels in a daily dose (2,500 mg Viracept/day) were predicted not to exceed a dose of approximately 2.75 mg/day (approximately 0.055 mg/kg/day based on 50 kg patient). As existing toxicology data on EMS did not permit an adequate patient risk assessment, a comprehensive animal toxicology evaluation of EMS was conducted. General toxicity of EMS was investigated in rats over 28 days. Two studies for DNA damage were performed in mice; chromosomal damage was assessed using a micronucleus assay and gene mutations were detected using the MutaMouse transgenic model. In addition, experiments designed to extrapolate animal exposure to humans were undertaken. A general toxicity study showed that the toxicity of EMS occurred only at doses >or= 60 mg/kg/day, which is far above that received by patients. Studies for chromosomal damage and mutations in mice demonstrated a clear threshold effect with EMS at 25 mg/kg/day, under chronic dosing conditions. Exposure analysis (Cmax) demonstrated that approximately 370-fold higher levels of EMS than that ingested by patients, are needed to saturate known, highly conserved, error-free, mammalian DNA repair mechanisms for alkylation. In summary, animal studies suggested that patients who took nelfinavir mesylate with elevated levels of EMS are at no increased risk for carcinogenicity or teratogenicity over their background risk, since mutations are prerequisites for such downstream events. These findings are potentially relevant to >40 marketed drugs that are mesylate salts.

  6. Valence and ionic lowest-lying electronic states of ethyl formate as studied by high-resolution vacuum ultraviolet photoabsorption, He(I) photoelectron spectroscopy, and ab initio calculations

    Energy Technology Data Exchange (ETDEWEB)

    Śmiałek, M. A., E-mail: smialek@pg.gda.pl [Department of Control and Energy Engineering, Faculty of Ocean Engineering and Ship Technology, Gdańsk University of Technology, Gabriela Narutowicza 11/12, 80-233 Gdańsk (Poland); Łabuda, M.; Guthmuller, J. [Department of Theoretical Physic and Quantum Information, Faculty of Applied Physics and Mathematics, Gdańsk University of Technology, Gabriela Narutowicza 11/12, 80-233 Gdańsk (Poland); Hubin-Franskin, M.-J.; Delwiche, J. [Département de Chimie, Université de Liège, Institut de Chimie-Bât. B6C, B-4000 Liège (Belgium); Duflot, D. [Laboratoire de Physique des Lasers, Atomes et Molécules (PhLAM), UMR CNRS 8523, Université Lille1 Sciences et Technologies, F-59655 Villeneuve d' Ascq Cedex (France); Mason, N. J. [Department of Physical Sciences, The Open University, Walton Hall, Milton Keynes MK7 6AA (United Kingdom); Hoffmann, S. V.; Jones, N. C. [ISA, Department of Physics and Astronomy, Aarhus University, Ny Munkegade 120, Building 1520, DK-8000 Aarhus C (Denmark); Limão-Vieira, P., E-mail: plimaovieira@fct.unl.pt [Laboratório de Colisões Atómicas e Moleculares, CEFITEC, Departamento de Física, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal)

    2014-09-14

    The highest resolution vacuum ultraviolet photoabsorption spectrum of ethyl formate, C{sub 2}H{sub 5}OCHO, yet reported is presented over the wavelength range 115.0–275.5 nm (10.75–4.5 eV) revealing several new spectral features. Valence and Rydberg transitions and their associated vibronic series, observed in the photoabsorption spectrum, have been assigned in accordance with new ab initio calculations of the vertical excitation energies and oscillator strengths. Calculations have also been carried out to determine the ionization energies and fine structure of the lowest ionic state of ethyl formate and are compared with a newly recorded He(I) photoelectron spectrum (from 10.1 to 16.1 eV). New vibrational structure is observed in the first photoelectron band. The photoabsorption cross sections have been used to calculate the photolysis lifetime of ethyl formate in the upper stratosphere (20–50 km)

  7. Cosmeceutical effect of ethyl acetate fraction of Kombucha tea by intradermal administration in the skin of aged mice.

    Science.gov (United States)

    Pakravan, Nafiseh; Mahmoudi, Elaheh; Hashemi, Seyed-Ali; Kamali, Jamal; Hajiaghayi, Reza; Rahimzadeh, Mitra; Mahmoodi, Vajiheh

    2017-11-19

    Natural ingredients have been always an interesting approach to prolong youthful appearance of skin. One of the natural compounds is Kombucha tea (KT), which has been mainly used as an energy drink in Asian countries for a long time. Previous reports indicated that it has pharmaceutical and favorable wound repairing effects. The beneficial properties of KT are thought to be mainly due to the presence of fermentation products such as flavonoids and other polyphenols with inhibition of hydrolytic and oxidative enzymes and anti-inflammatory effects. These properties prompted us to study the anti-aging potential of KT and investigate its effective fraction in aged mice, METHODS: Kombucha tea was fractionated into chloroform, butanol, and ethyl acetate, and flavonoid content was determined. Young and old mice were used as control. KT ethyl acetate fraction (KEAf), which had the highest flavonoid content, was intradermally administered to old mice. Administration of KEAf significantly increased the collagen content, NAD + /NADH level, and concomitantly improved skin connective tissue abnormalities in the aged skin. No sensitivity or irritation was observed. This finding suggested that KEAf can be a suitable candidate as a cosmetic product to improve aging-related skin abnormalities and regeneration of aged skin. © 2017 Wiley Periodicals, Inc.

  8. Antibacterial Activity of the Isolation Ethyl Acetate-Soluble Extract Noni Fruit (Morindra citrifolia L.) against Meat Bacterial Decay

    Science.gov (United States)

    Nugraheni, E. R.; Nurrakhman, M. B. E.; Munawaroh, H.; Saputri, L.

    2017-02-01

    Noni (Morindra citrifolia L.) is native to Indonesia which have medicinal properties. One of them as an antibacterial. This study aims to determine the antibacterial activity of isolates from the ethanol extract noni fruit to bacterial decay meat is Bacillus licheniformis, Klebsiella pneumonia, Bacillus alvei, Acinetobacter calcoaceticus, and Staphylococcus saprophyticus. The extraction process using the maceration method, and then made a partition by centrifugation ethyl acetate. Soluble part partition showed bacterial growth inhibition activity of the strong to very strong. Furthermore, the ethyl acetate soluble partition on preparative thin layer chromatography produced 5 isolates. Isolates obtained antibacterial activity test performed with a concentration of 20% and 30%. The results of antibacterial test against bacteria test isolates, showing isolates A can not inhibit the growth of bacteria, isolates B and C have medium activity and strong, isolates D and E isolates have activity against bacteria that were tested. MIC and MBC test results showed that the isolates B gives an inhibitory effect (bacteriostatic) against all bacteria. Content analysis of compounds by TLC using the reagents cerium (IV) sulfate indicates a phenol group. Isolates B contains a major compound which can be used as an antibacterial candidate in food preservation replace chemical preservatives.

  9. Ethyl chitosan synthesis and quantification of the effects acquired after grafting it on a cotton fabric, using ANOVA statistical analysis.

    Science.gov (United States)

    Popescu, Vasilica; Muresan, Augustin; Popescu, Gabriel; Balan, Mihaela; Dobromir, Marius

    2016-03-15

    Three ethyl chitosans (ECSs) have been prepared using the ethyl chloride (AA) that was obtained in situ. Each ECS was applied on a 100% cotton fabric through a pad-dry-cure technology. Using the ANOVA as statistic method, the wrinkle-proofing effects have been determined varying the concentrations of AA (0.1-2.1mmol) and chitosan (CS) (0.1-2.1mmol). Alkylation and grafting mechanisms have been confirmed by the results of FTIR, (1)H NMR, XPS, SEM, DSC and termogravimetric analyses. The performances of each ECS as wrinkle-proofing agent have been revealed through quantitative methods (taking-up degree, wrinkle-recovering angle, tensile strength and effect's durability). The ECSs confer wrinkle-recovering angle and tensile strength higher than those of the witness sample. Durability of ECSs grafted on cotton have been demonstrated by a good capacity of dyeing with non-specific (acid/anionic and cationic) dyes under severe working conditions (100°C, 60min) and a good antimicrobial capacity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Acute toxicity profiling of the ethyl acetate fraction of Swietenia macrophylla seeds and in-vitro neuroprotectio

    Directory of Open Access Journals (Sweden)

    Mustak Sayyad

    2017-02-01

    Full Text Available Swietenia macrophylla (SM is a medicinally important plant found in tropical and subtropical regions of the world. The ethyl acetate fraction of the seeds of S. macrophylla (SMEAF is reported to exhibit potent anticancer, antitumor, anti-inflammatory and antifeedant activities. Till date, there have been no studies reported on the acute oral toxicity profile of the ethyl acetate fraction of the seeds of SM. The objective of the present study was to determine the acute toxicity of SMEAF and evaluate the in-vitro neuroprotective activity of SMEAF using primary neuronal cell cultures. In acute oral toxicity study, the SMEAF did not produce any lethal signs of morbidity and mortality. Histo-pathological findings, support the safety of SMEAF, as there were no significant changes observed in any of the parameters studied. Based on the results obtained in MTT assay, we infer that SMEAF has a significant neuroprotective effect, as it increased the cell viability and exhibited protection to the neuronal cells against TBHP induced oxidative stress. Thus, SMEAF can be suggested for use in the development of herbal drug formulations with neuroprotective potential.

  11. 1-{2-[4-(4-Nitrophenylpiperazin-1-yl]ethyl}-4-aza-1-azoniabicyclo[2.2.2]octane iodide

    Directory of Open Access Journals (Sweden)

    Anssi Peuronen

    2012-07-01

    Full Text Available The title compound, C18H28N5O2+·I−, was observed as a main product in an intended 1:1 reaction between 4-iodonitrobenzene and 1,4-diazabicyclo[2.2.2]octane (DABCO. In the reaction, DABCO undergoes a ring opening to yield a quaternary salt of DABCO and 1-ethyl-4-(4-nitrophenylpiperazine with an iodide anion. The crystal structure determination was carried out as no crystal structure had been previously reported in the investigations describing the corresponding reaction with 4-chloronitrobenze. Indeed, the crystal structure of the title compound confirms the molecular composition proposed earlier for the analogous chloride salt. The cation conformation is similar to the previously reported dinitro analogue 1-{2-[4-(2,4-dinitrophenylpiperazin-1-yl]ethyl}-4-aza-1-azoniabicyclo[2.2.2]octane chloride [Clegg et al. (2004. Acta Cryst. E60, o291–o293]. The crystal packing is dominated by cation...I− interactions in addition to weak intermolecular C—H...O2N and C—H...N interactions between the cations.

  12. Development of a hybrid fermentation-enzymatic bioprocess for the production of ethyl lactate from dairy waste.

    Science.gov (United States)

    Koutinas, Michalis; Menelaou, Maria; Nicolaou, Evrydiki N

    2014-08-01

    This work explores the potential for the development of a hybrid fermentation-enzymatic process for the production of ethyl lactate from dairy waste. Cheese whey was used in Kluyveromyces marxianus and Lactobacillus bulgaricus batch cultures to produce ethanol and lactic acid respectively. Subsequently, the fermentation products were transferred into an organic phase through liquid-liquid extraction and ethyl lactate was formed in an esterification reaction catalyzed by lipases. The production of ethanol and lactic acid achieved under different conditions was 23gL(-1) and 29gL(-1), respectively. Furthermore, the efficiency of various organic solvents for the esterification reaction was evaluated and toluene was chosen for application in the process. The effect of water content was determined aiming to maximize the product yield and 40mgml(-1) was the optimal enzyme concentration. The bioprocess achieved maximum conversion of 33% constituting a valuable alternative to the application of energy demanding chemically derived methods. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Estimation of alcohol consumption during “Fallas” festivity in the wastewater of Valencia city (Spain) using ethyl sulfate as a biomarker

    Energy Technology Data Exchange (ETDEWEB)

    Andrés-Costa, María Jesús, E-mail: M.Jesus.Andres@uv.es [Environmental and Food Safety Research Group (SAMA-UV), Desertification Research Centre CIDE (CSIC-UV-GV), Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, Burjassot, 46100 Valencia (Spain); Escrivá, Úrsula [Environmental and Food Safety Research Group (SAMA-UV), Desertification Research Centre CIDE (CSIC-UV-GV), Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, Burjassot, 46100 Valencia (Spain); Andreu, Vicente [Lanscape Chemistry and Environmental Forensics Group, CIDE (CSIC-UV-GV), Carretera Moncada, Náquera, Km. 4.5, Moncada, 46113 Valencia (Spain); Picó, Yolanda [Environmental and Food Safety Research Group (SAMA-UV), Desertification Research Centre CIDE (CSIC-UV-GV), Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, Burjassot, 46100 Valencia (Spain)

    2016-01-15

    Alcohol consumption has been increasing in the last years and it has become a sociological problem due its derived health and safety problems. Ethyl sulfate is a secondary metabolite of the alcohol degradation that is excreted through the urine (0.010–0.016%) after alcohol ingestion and it is quite stable in water. In this study, a new methodology to determine ethyl sulfate by ion-pair liquid chromatography-tandem mass spectrometry (LC–MS/MS) was developed. Different ion-pairs and additives were tested directly in the sample extracts or in the mobile phase. The best ion-pair was set up adding 0.5 M of tributylamine and 0.1% of formic acid to the sample. The limit of quantification was 0.3 μg L{sup −1} and the intra-day and inter-day precision of the method were ≤ 2.8 and ≤ 3.0%, respectively. Good linearity (r{sup 2} < 0.999) and low matrix effect (< 30% corrected by using internal isotopically labelled internal standard) were achieved. The sampling campaign was from 4th to 20th March of 2014 covering the festivity of Fallas (15th to 19th March). Ethyl sulfate was determined in all influents of the 3 wastewater treatment plants (Pinedo I, Pinedo II and Quart-Benàger) belonging to Valencia and surrounding area. Ethyl sulfate concentrations ranged from 1.46 to 19.85 μg L{sup −1} and alcohol consumption ranged from 1.07 to 56.11 mL day{sup −1} inhab{sup −1}, being the highest value of alcohol consumption determined during Fallas. This study presents a reliable and alternative method to traditional ones to determine alcohol consumption by population that provides real-time information of alcohol consumption. - Highlights: • Direct determination of ethyl sulfate in wastewater by ion-pair LC–MS/MS • Different ion-pairs and additives were tested and compared. • Sewage epidemiology was applied to estimate alcohol consumption. • The increase in the alcohol consumption during Fallas festivity is noticeable.

  14. CCDC 721713: Experimental Crystal Structure Determination : Dichloro-(ethyl phenylalaninate)-tris(pyridine)-ruthenium(ii)

    KAUST Repository

    Reiner, Thomas

    2013-01-01

    An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

  15. The effects of structural and microenvironmental disorder on the electronic properties of poly[2-methoxy,5-(2 '-ethyl-hexoxy)-1,4-phenylene vinylene] (MEH-PPV) and related oligomers

    NARCIS (Netherlands)

    Wachsmann-Hogiu, S; Peteanu, LA; Liu, LA; Yaron, DJ; Wildeman, J

    2003-01-01

    In this study, electroabsorption (Stark) spectroscopy is used to determine the trace of the change in polarizability (tr (Delta x) over bar) and the absolute value of the change in dipole moment (/Delta(mu) over right arrow/) of the electroluminescent polymer poly [2-methoxy,5-(2'-ethyl-hexoxy)-

  16. Theoretical and Shock Tube Study of the Rate Constants for Hydrogen Abstraction Reactions of Ethyl Formate

    KAUST Repository

    Wu, Junjun

    2017-08-03

    We report a systematic chemical kinetics study of the H-atom abstractions from ethyl formate (EF) by H, O(3P), CH3, OH, and HO2 radicals. The geometry optimization and frequency calculation of all the species were conducted using the M06 method and the cc-pVTZ basis set. The one-dimensional hindered rotor treatment of the reactants and transition states and the intrinsic reaction coordinate analysis were also performed at the M06/cc-pVTZ level of theory. The relative electronic energies were calculated at the CCSD(T)/cc-pVXZ (where X = D, T) level of theory and further extrapolated to the complete basis set limit. Rate constants for the tittle reactions were calculated over the temperature range of 500‒2500 K by the transition state theory (TST) in conjunction with asymmetric Eckart tunneling effect. In addition, the rate constants of H-abstraction by hydroxyl radical were measured in shock tube experiments at 900‒1321 K and 1.4‒2.0 atm. Our theoretical rate constants of OH + EF → Products agree well with the experimental results within 15% over the experimental temperature range of 900‒1321 K. Branching ratios for the five types of H-abstraction reactions were also determined from their individual site-specific rate constants.

  17. Signal transduction events in lung injury induced by 2-chloroethyl ethyl sulfide, a mustard analog.

    Science.gov (United States)

    Chatterjee, Diptendu; Mukherjee, Shyamali; Smith, Milton G; Das, Salil K

    2003-01-01

    Sulfur mustard has been used as a vesicant chemical warfare agent. To understand the mechanism by which mustard gas exposure causes respiratory damage, we have used 2-chloroethyl ethyl sulfide (CEES) as a mustard analog. Our initial studies have shown that guinea pigs exposed to CEES intratracheally accumulate high levels of TNF-alpha. Accumulation of TNF-alpha leads to activation of both acid and neutral sphingomyelinases, resulting in high accumulation of ceramides, a second messenger involved in cell apoptosis. In addition, NF-kappa B was activated for a short period (1-2 h after exposure) as determined by mobility shift assay. Supershift assays indicated that both p50 and p65 of NF-kappa B were activated due to CEES exposure. However, NF-kappa B rapidly disappeared after 2 h. It is possible that the initial activation of NF-kappa B was an adaptive response to protect the cells from damage since NF-kappa B is known to inhibit TNF-alpha/ceramide-induced cell apoptosis. Since NF-kappa B disappeared after 2 h, the cells continued being damaged owing to accumulation of ceramides and activation of several caspases, leading to apoptosis. Copyright 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:114-121, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10068

  18. In vitro study of partially hydrolyzed poly(2-ethyl-2-oxazolines) as materials for biomedical applications.

    Science.gov (United States)

    Shah, Rushita; Kronekova, Zuzana; Zahoranová, Anna; Roller, Ladislav; Saha, Nabanita; Saha, Petr; Kronek, Juraj

    2015-04-01

    Polymers based on 2-oxazoline, such as poly(2-ethyl-2-oxazolines) (PETOx), are considered to be a type of 'pseudopeptide' with the ability to form novel biomaterials. The hydrolysis of PETOx was carried out to evaluate its use in biomedical applications. In the present work, PETOx samples with a range of molar masses were prepared by living cationic polymerization. Hydrolysis was carried out at time intervals ranging from 15 to 180 min to prepare copolymers with different amounts of ethylene imine units. (1)H NMR spectroscopy was used to identify the structure of the hydrolyzed polymers. The dependence of in vitro cell viability on the degree of hydrolysis was determined using three different model cell lines, namely, mouse embryonic 3T3 fibroblasts, pancreatic βTC3 cells, and mouse lymphoid macrophages P388.D1. It was demonstrated that increasing the degree of hydrolysis decreased cell viability for all cell types. Fibroblast cells displayed the highest tolerance; additionally, the effect of polymer size showed no observable significance. Macrophage cells, immune system representatives, displayed the highest sensitivity to contact with hydrolyzed PETOx. The effect of polymer hydrolysis, polymer concentration and the incubation time on cell viability was experimentally observed. Confocal laser-scanning microscopy provided evidence of cellular uptake of pyrene-labeled (co)polymers.

  19. The effect of sugars on the retention of ethyl butyrate by gellan gels.

    Science.gov (United States)

    Evageliou, Vasiliki; Patsiakou, Anna

    2014-08-15

    The effect of sucrose, glucose and fructose on the retention of ethyl butyrate by low acyl gellan gels was investigated by static headspace gas chromatography. The air/biopolymer partition coefficient (K) and percentage of retention (R%) were determined. When 5 g of sample were left to equilibrate at 37 °C for 24 h, the obtained results were explained in terms of gel rigidity, as increased rigidity resulted in increased aroma retention. Glucose showed the greatest aroma release among the sugars and resulted in either the same or increased aroma release with increasing concentration. Increasing concentrations of fructose and sucrose did not alter aroma release significantly. For 15 g of sample mass, sucrose exhibited the lowest partition coefficient values among the sugars. The two higher sucrose concentrations resulted in decreased coefficient values. For fructose and glucose, aroma retention decreased with increasing concentration. The percentage of retention values were positive for all sugars, throughout their concentration range and for both experiments. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Pharmacokinetic equivalence of 5(ethyl(/sup 2/H)5)- and unlabelled phenobarbitone

    Energy Technology Data Exchange (ETDEWEB)

    Benchekroun, Y.; Ribon, B.; Falconnet, J.B.; Cherrah, Y.; Brazier, J.L.

    1989-02-01

    The present study shows the absence of in vivo pharmacokinetic isotope effect on phenobarbitone (PB) C5-ethyl deuteration (PBd5) following oral administration to man of equimolar PB/PBd5 mixtures (0.40 mmol each). Plasma PB and PBd5 (17 days) and urine PB, PBd5 and parahydroxy-metabolites (PBOH, PBHOd5) levels were determined by GC-MS. Isotope effect research includes comparison of pharmacokinetic parameters, study of time-dependence of isotope ratios (IRs) in plasma and urine (linearity test), comparison of IRs between samples and administered mixtures (Mann Whitney's test) and comparison of PBOH/PBOHd5 ratios before and after urine enzymatic hydrolysis (Student's two tailed t-test). No significant isotope effect was observed on pharmacokinetic parameters, PB hydroxylation or PBOH conjugation (x less than or equal to 5%); which the absence of pentadeuteration-induced alteration in PB's HSA binding parameters (binding mode, Ka, N) corroborates (x less than or equal to 5%). These results establish bioequivalence of PB and PBd5; the latter can be used with benefit in stable-isotope clinical pharmacology (steady state pharmacokinetics, drug interactions...) investigations as well as bioavailability studies of PB preparations.

  1. Pengaruh Ethyl Methane Sulphonate (EMS Terhadap Pertumbuhan dan Variasi Tanaman Marigold (Tagetes sp.

    Directory of Open Access Journals (Sweden)

    NI MADE DIAN PRATIWI

    2015-09-01

    Full Text Available The Effect of Ethyl Methane Sulphonate (EMS on Growth and Variations of Marigold (Tagetes sp. The aims of this research are to determine the variation of marigold (Tagetes sp derived from seed treated with EMS and to recommend the EMS concentrations that are able to induce varietion. Seeds of marigold cv Narai Orange were soaked in water for 6 hours, followed by soaking in EMS at concentration of 0%, 0.3%, 0.6% and 0.9% for 4 hours. This study employed Randomized Complete Blok Design with 10 replicates and each replicate consisted of 10 plants. Six plants were randomly chosen for measurements. The total number of samples observed were 240 plants. Observations were made on the percentage of the growth, plant height, number of leaves, number of branches, diameter and weight of flowers. Data obtained from the observations were analyzed using Analysis of Variance (ANOVA, followed by DMRT (Duncan’s Multiple Range Test if there is a significant difference between treatments. The EMS treatment reduced all characters observed. The EMS concentration of 0.6% showed plant that had yellow flowers. The 0.9% EMS treatment resulted in one plant with chimera, 6 dwarf plants, 2 plants with thin stems, and 1 short plant with many branches. Untreated plants did not show any variation.

  2. Manipulation of Polyhydroxybutyrate Properties through Blending with Ethyl-Cellulose for a Composite Biomaterial

    Directory of Open Access Journals (Sweden)

    Rodman T. H. Chan

    2011-01-01

    Full Text Available Polyhydroxybutyrate (PHB is widely used as a biomaterial in medical and tissue-engineering applications, a relatively high crystallinity limits its application. Blending PHB with ethyl-cellulose (EtC was readily achieved to reduce PHB crystallinity and promote its degradation under physiological conditions without undue influence on biocompatibility. Material strength of composite films remained unchanged at 6.5 ± 0.6 MPa with 40% (w/w EtC loadings. Phase separation between the two biopolymers was determined with PHB crystallinity decreasing from 63% to 47% for films with the same loading. This reduction in crystallinity supported an increase in the degradation rates of composite films from 0.39 to 0.81% wk−1 for PHB and its composite, respectively. No significant change in morphology and proliferation of olfactory ensheathing cells were observed with the composites despite significant increases in average surface roughness (Ra of the films from 2.90 to 3.65 μm for PHB and blends with 80% (w/w EtC, respectively.

  3. Ethyl acetate-n-butanol gradient solvent system for high-speed countercurrent chromatography to screen bioactive substances in okra.

    Science.gov (United States)

    Ying, Hao; Jiang, Heyuan; Liu, Huan; Chen, Fangjuan; Du, Qizhen

    2014-09-12

    High-speed countercurrent chromatographic separation (HSCCC) possesses the property of zero-loss of sample, which is very useful for the screening of bioactive components. In the present study, the ethyl acetate-n-butanol gradient HSCCC solvent system composed of n-hexane-ethyl acetate-n-butanol-water was investigated for the screening of bioactive substances. To screen the antiproliferative compounds in okra extract, we used the stationary phase ethyl acetate-n-butanol-water (1:1:10) as the stationary phase, and eluted the antiproliferative components by 6-steps of gradient using mobile phases n-hexane-ethyl acetate (1:2), n-hexane-ethyl acetate (1:4), n-hexane-ethyl acetate (0:4), n-butanol-ethyl acetate (1:4) n-butanol-ethyl acetate (1:2), n-butanol-ethyl acetate (2:2), and n-butanol-ethyl acetate (2:1). The fractions collected from HSCCC separation with the gradient solvent system were assayed for antiproliferative activity against cancer cells. Bioactive components were identified: a major anti-cancer compound, 4'-hydroxy phenethyl trans-ferulate, with middle activity, and a minor anti-cancer compound, carolignan, with strong activity. The result shows that the gradient solvent system is potential for the screening of bioactive compounds from natural products. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Determination of GHB and GHB-β-O-glucuronide in hair of three narcoleptic patients-Comparison between single and chronic GHB exposure

    DEFF Research Database (Denmark)

    Mehling, Lena-Maria; Wang, Xin; Johansen, Sys-Stybe

    2017-01-01

    (®) in a total dose of 5.78g GHB at bed time (2.89g) and four hours (2.89g) later. P2 took a dose of 3.10g GHB at bed time and an additional dose of 2.68g GHB four hours later. Patient 3 (P3) was newly diagnosed with narcolepsy and started his therapy with oral dose of 6g (divided in three portions of 2g GHB...

  5. Ultra-high-performance liquid chromatography tandem mass spectrometry determination of GHB, GHB-glucuronide in plasma and cerebrospinal fluid of narcoleptic patients under sodium oxybate treatment

    DEFF Research Database (Denmark)

    Tittarelli, Roberta; Pichini, Simona; Pedersen, Daniel S

    2017-01-01

    Sodium oxybate (Xyrem®), the sodium salt of γ- hydroxybutyric acid (GHB), is a first-line treatment of the symptoms induced by type 1 narcolepsy (NT1) and it is highly effective in improving sleep architecture, decreasing excessive daytime sleepiness and the frequency of cataplexy attacks. Using...... with no differences to those of control individuals. In conclusion this simple and fast UHPLC-MS/MS method proved useful for pharmacokinetic studies and therapeutic drug monitoring of GHB in narcoleptic patients treated with sodium oxybate....

  6. Crude ethyl acetate extract of marine microalga, Chaetoceros calcitrans, induces Apoptosis in MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Goh, Su Hua; Alitheen, Noorjahan Banu Mohamed; Yusoff, Fatimah Md; Yap, Swee Keong; Loh, Su Peng

    2014-01-01

    Marine brown diatom Chaetoceros calcitrans and green microalga Nannochloropsis oculata are beneficial materials for various applications in the food, nutraceutical, pharmaceutical and cosmeceutical industries. This study investigated cytotoxicity of different crude solvent extracts from C. calcitrans and N. oculata against various cancer cell lines. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was carried out to screen the cytotoxic effects of hexane (Hex), dichloromethane (DCM), ethyl acetate, and methanol extract from C. calcitrans and N. oculata toward various cancer cell lines. Flow cytometry cell cycle was used to determine the cell cycle arrest while the mode of cell death was investigated through acridine orange/propidium iodide (AOPI) staining, Annexin V-Fluorescein Isothiocyanate (FITC) and Terminal deoxynucleotidyl transferase-mediated d-UTP Nick End Labeling (TUNEL) assays. Expression profile of apoptotic and proliferative-related genes was then determined using the multiplex gene expression profiler (GeXP). Crude ethyl acetate (CEA) extract of C. calcitrans inhibited growth of MDA-MB-231 cells, with IC50 of 60 μg/mL after 72 h of treatment. Further studies were conducted to determine the mode of cell death at various concentrations of this extract: 30, 60 and 120 μg/mL. The mode of cell death was mainly apoptosis as shown through apoptosis determination test. The expression data from GeXP showed that caspase-4 was upregulated while B-cell leukemia/lymphoma 2(Bcl-2) was down regulated. Thus, caspase-4 induction endoplasmic reticulum death pathway is believed to be one of the mechanisms underlying the induction of apoptosis while Bcl-2 induced S and G2/M cell cycle phase arrest in MDA-MB-231 cells. CEA extract of C. calcitrans showed the highest cytotoxicity on MDA-MB-231 via apoptosis.

  7. Identification and quantification of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide (THC-COOH-glu) in hair by ultra-performance liquid chromatography tandem mass spectrometry as a potential hair biomarker of cannabis use.

    Science.gov (United States)

    Pichini, Simona; Marchei, Emilia; Martello, Simona; Gottardi, Massimo; Pellegrini, Manuela; Svaizer, Fiorenza; Lotti, Andrea; Chiarotti, Marcello; Pacifici, Roberta

    2015-04-01

    We developed and validated an ultra-high-pressure liquid chromatography-tandem mass spectrometry method to identify and quantify 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide in hair of cannabis consumers. After hair washing with methyl alcohol and diethyl ether and subsequent addition of amiodarone as internal standard hair samples were treated with 500 μl VMA-T M3 buffer reagent for 1 h at 100 °C. After cooling, 10 μl VMA-T M3 extract were injected into chromatographic system. Chromatographic separation was carried out on a reversed phase column using a linear gradient elution with two solvents: 5 mM ammonium formate pH 3.0 (solvent A) and 0.1% formic acid in acetonitrile (solvent B). The flow rate was kept constant at 0.4 ml/min during the analysis. The separated analytes were detected with a triple quadrupole mass spectrometer operated in multiple reaction monitoring mode via positive electrospray ionization. Linear calibration curves were obtained for 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide with correlation coefficients (r(2)) of 0.99 and a limit of quantification of 0.25 pg/mg hair. Analytical recovery was between 79.6% and 100.7% and intra- and inter-assay imprecision and inaccuracy were always lower than 15%. Ultra-high-pressure liquid chromatography-tandem mass spectrometry analysis of 20 different hair samples of cannabis consumers disclosed the presence of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide in the range of 0.5-8.6 pg/mg hair. These data provided a good start to consider 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide as alternative hair biomarker of cannabis consumption. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Ethyl Pyruvate Ameliorates Hepatic Ischemia-Reperfusion Injury by Inhibiting Intrinsic Pathway of Apoptosis and Autophagy

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    Miao Shen

    2013-01-01

    Full Text Available Background. Hepatic ischemia-reperfusion (I/R injury is a pivotal clinical problem occurring in many clinical conditions such as transplantation, trauma, and hepatic failure after hemorrhagic shock. Apoptosis and autophagy have been shown to contribute to cell death in hepatic I/R injury. Ethyl pyruvate, a stable and simple lipophilic ester, has been shown to have anti-inflammatory properties. In this study, the purpose is to explore both the effect of ethyl pyruvate on hepatic I/R injury and regulation of intrinsic pathway of apoptosis and autophagy. Methods. Three doses of ethyl pyruvate (20 mg/kg, 40 mg/kg, and 80 mg/kg were administered 1 h before a model of segmental (70% hepatic warm ischemia was established in Balb/c mice. All serum and liver tissues were obtained at three different time points (4 h, 8 h, and 16 h. Results. Alanine aminotransferase (ALT, aspartate aminotransferase (AST, and pathological features were significantly ameliorated by ethyl pyruvate (80 mg/kg. The expression of Bcl-2, Bax, Beclin-1, and LC3, which play an important role in the regulation of intrinsic pathway of apoptosis and autophagy, was also obviously decreased by ethyl pyruvate (80 mg/kg. Furthermore, ethyl pyruvate inhibited the HMGB1/TLR4/ NF-κb axis and the release of cytokines (TNF-α and IL-6. Conclusion. Our results showed that ethyl pyruvate might attenuate to hepatic I/R injury by inhibiting intrinsic pathway of apoptosis and autophagy, mediated partly through downregulation of HMGB1/TLR4/ NF-κb axis and the competitive interaction with Beclin-1 of HMGB1.

  9. Gradual enhancement of ethyl acetate production through promoter engineering in chinese liquor yeast strains.

    Science.gov (United States)

    Dong, Jian; Hong, Kun-Qiang; Hao, Ai-Li; Zhang, Cui-Ying; Fu, Xiao-Meng; Wang, Peng-Fei; Xiao, Dong-Guang

    2018-01-05

    As content and proportion of ethyl acetate is critical to the flavor and quality of beverages, the concise regulation of the ethyl acetate metabolism is a major issue in beverage fermentations. In this study, for ethyl acetate yield regulation, we finely modulated the expression of ATF1 through precise and seamless insertion of serially truncated PGK1 promoter from the 3' end by 100bp steps in the Chinese liquor yeast, CLy12a. The three engineered promoters carrying 100-, 200-, and 300-bp truncations exhibited reduced promoter strength but unaffected growth. These three promoters were integrated into the CLy12a strain, generating strains CLy12a-P-100, CLy12a-P-200, and CLy12a-P-300, respectively. The transcription levels of CLy12a-P-100, CLy12a-P-200, and CLy12a-P-300 were 20%, 17%, and 10% of that of CLy12a-P, respectively. The AATase (alcohol acetyl transferases, encoded by the ATF1 gene) activity of three engineered strains were 36%, 56%, and 62% of that of CLy12a-P. In the liquid fermentation of corn hydrolysate at 30°C, the concentration of ethyl acetate in CLy12a-P-100, CLy12a-P-200, and CLy12a-P-300 were reduced by 28%, 30%, and 42%, respectively, compared to CLy12a-P. These results verifying that the ethyl acetate yield could be gradually enhanced by finely modulating the expression of ATF1. The engineered strain CLy12a-P-200 produced the ethyl acetate concentration with the best sensorial quality compared to the other engineered yeast strains. The method proposed in this work supplies a practical proposal for breeding Chinese liquor yeast strains with finely modulated ethyl acetate yield. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018. © 2018 American Institute of Chemical Engineers.

  10. Analysis of Veterinary Drug and Pesticide Residues Using the Ethyl Acetate Multiclass/Multiresidue Method in Milk by Liquid Chromatography-Tandem Mass Spectrometry

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    Husniye Imamoglu

    2016-01-01

    Full Text Available A rapid and simple multiclass, ethyl acetate (EtOAc multiresidue method based on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS detection was developed for the determination and quantification of 26 veterinary drugs and 187 total pesticide residues in milk. Sample preparation was a simple procedure based on liquid–liquid extraction with ethyl acetate containing 0.1% acetic acid, followed by centrifugation and evaporation of the supernatant. The residue was dissolved in ethyl acetate with 0.1% acetic acid and centrifuged prior to LC-MS/MS analysis. Chromatographic separation of analytes was performed on an Inertsil X-Terra C18 column with acetic acid in methanol and water gradient. The repeatability and reproducibility were in the range of 2 to 13% and 6 to 16%, respectively. The average recoveries ranged from 75 to 120% with the RSD (n=18. The developed method was validated according to the criteria set in Commission Decision 2002/657/EC and SANTE/11945/2015. The validated methodology represents a fast and cheap alternative for the simultaneous analysis of veterinary drug and pesticide residues which can be easily extended to other compounds and matrices.

  11. ISOLATION AND IDENTIFICATION OF FLAVONOID COMPOUND EXTRACTIRE ETHYL ACETATE FRACTION EXTRACTED FROM THE RHIZOMES FINGERROOT OF (Boesenbergia pandurata (Roxb. Schlecht (Zingiberaceae

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    Ochtavia Prima Sari

    2010-06-01

    Full Text Available Boesenbergia pandurata (Roxb. Schlecht is one of fingerroot plant in ginger family (Zingiberaceae. The rhizomes of the plant contained a lot of secondary metabolites compounds. Therefore, the purpose of the research is to isolate and identify the flavonoid compound from the plant. The rhizomes were extracted with metanol continued by partition using ethyl acetate-water (1:1. The ethyl acetate extract was chromatographed on a column of Si gel (Vacuum Liquid Chromatography and Gravitation Column Chromatography using n-hexane-ethyl acetate (5:2 as eluents. Further purification by recristalization  using benzene  produced a compound as yellow powder (16 mg having melting point of 294-295 oC. The spectra of isolated compound were determined by spectroscopic UV-Vis, FT-IR, and GC-MS. Spectrum UV-Vis of the isolated compound showed ultraviolet absorption at λmax (MeOH, nm 290 and 322; λmax (MeOH+NaOH, nm 322; λmax (MeOH+AlCl3, nm 309; λmax (MeOH+AlCl3+HCl, nm 310; λmax (MeOH+NaOAc, nm 322 and λmax (MeOH+NaOAc+H3BO3, nm 290. Its FT-IR spectrum represented a number of absorption lied on νmax (cm-1 : 3142.5; 3012.6; 2893; 2345.3; 1631.7; 1585.4; 1357.8; 1168.8; and 825.5. GC-MS spectrum of the isolated compound exhibited an [M]+ ion peak at m/z = 256 with retention time of  22,579. Based on the results of spectrum analysis it can be concluded that the compound is 5,7-dyhydroxyflavanone.   Keywords: 5,7-dyhydroxyflavanone, Boesenbergia pandurata, ethyl asetat, fingerroot

  12. Glutathione S-transferase pi (GST-pi) inhibition and anti-inflammation activity of the ethyl acetate extract of Streptomyces sp. strain MJM 8637.

    Science.gov (United States)

    Lee, Sung-Kwon; Lee, Dong-Ryung; Choi, Bong-Keun; Palaniyandi, Sasikumar Arunachalam; Yang, Seung Hwan; Suh, Joo-Won

    2015-11-01

    To investigate the anti-cancer properties of soil-borne actinobacteria, MJM 8637, the glutathione S-transferase pi (GST-pi) assay, anti-tumor necrosis factor (TNF)-α assay, the level of antioxidant potential by DPPH radical scavenging activity, NO scavenging activity, and ABTS radical scavenging activity in ethyl acetate extract were determined. The 16S rDNA sequencing analysis revealed that Streptomyces sp. strain MJM 8637, which was isolated from Hambak Mountain, Korea, has 99.5% similarity to Streptomyces atratus strain NBRC 3897. The physiological and the morphological characteristics of the strain MJM 8637 were also identified. The ethyl acetate extract of MJM 8637 inhibited TNF-α production approximately 61.8% at concentration 100 μg/ml. The IC50 value of the strain MJM 8637 extract on GST-pi was identified to be 120.2 ± 1.6 μg/ml. In DPPH, NO, and ABTS radical scavenging assays, the IC50 values of the strain MJM 8637 extract were found to be 977.2 μg/ml, 1143.7 μg/ml, and 454.4 μg/ml, respectively. The ethyl acetate extract of the strain MJM 8637 showed 97.2 ± 1.3% of cell viability at 100 μg/ml in RAW 264.7 cell viability assay. The results obtained from this study suggest that the ethyl acetate extract of Streptomyces sp. strain MJM 8637 could be considered as a potential source of drug for the cancers that have multidrug resistance with its GST-pi inhibition and anti-inflammation activities, and low cytotoxicity.

  13. Effects of ethyl oleate and microwave blanching on drying kinetics of bitter gourd.

    Science.gov (United States)

    Srimagal, A; Mishra, S; Pradhan, R C

    2017-04-01

    In the present study effects of pre-treatments such as blanching with hot water and microwave, ethyl oleate dipping, and combinations of these treatments on drying characteristics of the bitter gourd ( Momordica charantia L.) at various temperature were studied. The overall drying time was reduced significantly in the ethyl oleate treated and microwave blanched samples. The minimum diffusivity (2.65 × 10 -8  m 2 /s) was observed in control samples whereas the maximum diffusivity (3.86 × 10 -8  m 2 /s) was observed in ethyl oleate treated and microwave blanched samples at 50 °C. Ethyl oleate treated and microwave blanched samples dried at lowest temperature (50 °C) showed the lowermost shrinkage ratio (46.04%). The rehydration ratio increased from 3.49 to 4.90 as the temperature increased from 50 to 70 °C for control samples. Combined pre-treatment of ethyl oleate and microwave blanching had resulted in most acceptable drying characteristics and quality of bitter gourd. Drying of the samples were mathematically modelled. The drying characteristics of bitter gourd could be explained suitably by Page drying model.

  14. Effects of ethyl chloride spray on pain and parameters of needle electromyography in the upper extremity.

    Science.gov (United States)

    Moon, Young-Eun; Kim, Sang-Hyun

    2014-10-01

    The aim of this study was to compare the effects of ethyl chloride and placebo sprays for reducing pain induced by needle electromyography and changes in parameters of the motor unit action potential during needle electromyography of the upper extremity. Sixty patients were randomized into the ethyl chloride or placebo spray groups. In both groups, spray was applied just before needle electromyography of the flexor carpi radialis, and a visual analog scale to evaluate the pain of needle electromyography and a five-point Likert scale for patient satisfaction and preference for reexamination were compared between the two groups. Then, changes in the amplitude, phases, turns, and duration of the motor unit action potential during needle electromyography of the biceps brachii were compared before and after spraying in each group. The visual analog scale was significantly lower, and patient satisfaction and preference for reexamination were significantly higher in the ethyl chloride spray group. Among the parameters of the motor unit action potential, there were no significant changes except for an increased duration after spraying with ethyl chloride. Ethyl chloride spray can effectively reduce pain, but it must be used with caution because it may affect parameters of the motor unit action potential during needle electromyography.

  15. Surface-enhanced Raman scattering for quantitative detection of ethyl carbamate in alcoholic beverages.

    Science.gov (United States)

    Yang, Danting; Zhou, Haibo; Ying, Yibin; Niessner, Reinhard; Haisch, Christoph

    2013-11-01

    Ethyl carbamate, a by-product of fermentation and storage with widespread occurrence in fermented food and alcoholic beverages, is a compound potentially toxic to humans. In this work, a new approach for quantitative detection of ethyl carbamate in alcoholic beverages, based on surface-enhanced Raman scattering (SERS), is reported. Individual silver-coated gold nanoparticle colloids are used as SERS amplifiers, yielding high Raman enhancement of ethyl carbamate in three kinds of alcoholic beverages (vodka, Obstler, and white rum). The characteristic band at 1,003 cm(-1), which is the strongest and best reproducible peak in the SERS spectra, was used for quantitative evaluation of ethyl carbamate. The limit of detection, which corresponds to a signal-to-noise ratio of 3, was 9.0 × 10(-9) M (0.8 μg · L(-1)), 1.3 × 10(-7) M (11.6 μg · L(-1)), and 7.8 × 10(-8) M (6.9 μg · L(-1)), respectively. Surface-enhanced Raman spectroscopy offers great practical potential for the in situ assessment and identification of ethyl carbamate in the alcoholic beverage industry.

  16. Enzymatic production of biodiesel from microalgal oil using ethyl acetate as an acyl acceptor.

    Science.gov (United States)

    Alavijeh, Razieh Shafiee; Tabandeh, Fatemeh; Tavakoli, Omid; Karkhane, Aliasghar; Shariati, Parvin

    2015-01-01

    Microalgae have become an important source of biomass for biodiesel production. In enzymatic transesterification reaction, the enzyme activity is decreased in presence of alcohols. The use of different acyl acceptors such as methyl/ethyl acetate is suggested as an alternative and effective way to overcome this problem. In this study, ethyl acetate was used for the first time in the enzymatic production of biodiesel by using microalga, Chlorella vulgaris, as a triglyceride source. Enzymatic conversion of such fatty acids to biodiesel was catalyzed by Novozym 435 as an efficient immobilized lipase which is extensively used in biodiesel production. The best conversion yield of 66.71% was obtained at the ethyl acetate to oil molar ratio of 13:1 and Novozym 435 concentration of 40%, based on the amount of oil, and a time period of 72 h at 40℃. The results showed that ethyl acetate have no adverse effect on lipase activity and the biodiesel amount was not decreased even after seven transesterification cycles, so ethyl acetate has a great potential to be substituted for short-chain alcohols in transesterification reaction.

  17. The anti-inflammatory effects of Caragana tangutica ethyl acetate extract.

    Science.gov (United States)

    Niu, Xiaofeng; Li, Yongmei; Li, Weifeng; Hu, Hua; Yao, Huan; Li, Huani; Mu, Qingli

    2014-02-27

    Caragana tangutica KOM has been used to treat arthritis, wounds, fever and other disease conditions in traditional Chinese medicine (TMC). To support the application of the plant in traditional Chinese medicine by investigating the anti-inflammatory effects of the ethyl acetate extract of Caragana tangutica. The anti-inflammatory activity was evaluated by animal models including xylene-induced ear edema in mice, carrageenan-induced paw edema in rats, acetic acid induced writhing in mice and LPS-induced acute lung injury (ALI). The anti-inflammatory mechanism was evaluated by detecting prostaglandin E2 and immunohistochemistry expression of cyclooxygenase-2 (COX-2) using an EIA assay kit and immunohistochemistry, respectively. The results showed that the xylene-induced ear edema in mice was significantly reduced by the ethyl acetate extract at dosages of 100, 200 and 400mg/kg, and the carrageenan-induced paw edema in rats was monitored to be reduced by the ethyl acetate extract 3h after carrageenan injection. The ethyl acetate extract was also found to reduce the inflammation pain of acetic acid-induced writhing model in a dose-dependent manner and cause reduction of the ALI in mice through the inhibition of the release of PGE2 and the LPS-induced COX-2 expression in the lung. Our study demonstrates that the ethyl acetate extract of the plant can help to reduce inflammations by inhibiting the expression of COX-2. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Formation of ethyl acetate from whey by Kluyveromyces marxianus on a pilot scale.

    Science.gov (United States)

    Löser, Christian; Urit, Thanet; Stukert, Anton; Bley, Thomas

    2013-01-10

    Whey arising in huge amounts during milk processing is a valuable renewable resource in the field of White Biotechnology. Kluyveromyces marxianus is able to convert whey-borne lactose into ethyl acetate, an environmentally friendly solvent. Formation of ethyl acetate as a bulk product is triggered by iron (Fe). K. marxianus DSM 5422 was cultivated aerobically in whey-borne medium originally containing 40 μg/L Fe, supplemented with 1, 3 or 10 mg/L Fe in the pre-culture, using an 1 L or 70 L stirred reactor. The highest Fe content in the pre-culture promoted yeast growth in the main culture causing a high sugar consumption for growth and dissatisfactory formation of ethyl acetate, while the lowest Fe content limited yeast growth and promoted ester synthesis but slowed down the process. An intermediate Fe dose (ca. 0.5 μg Fe/g sugar) lastly represented a compromise between some yeast growth, a quite high yield of ethyl acetate and an acceptable duration of the process. The mass of ethyl acetate related to the sugar consumed amounted to 0.113, 0.265 and 0.239 g/g in the three processes corresponding to 21.9%, 51.4% and 46.3% of the theoretically maximum yield. The performance on a pilot scale was somewhat higher than on lab scale. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Effect of potent ethyl acetate fraction of Stereospermum suaveolens extract in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Balasubramanian, T; Chatterjee, Tapan Kumar; Senthilkumar, G P; Mani, Tamizh

    2012-01-01

    To evaluate the antihyperglycemic effect of ethyl acetate fraction of ethanol extract of Stereospermum suaveolens in streptozotocin-(STZ-) induced diabetic rats by acute and subacute models. In this paper, various fractions of ethanol extract of Stereospermum suaveolens were prepared and their effects on blood glucose levels in STZ-induced diabetic rats were studied after a single oral administration (200 mg/kg). Administration of the ethyl acetate fraction at 200 mg/kg once daily for 14 days to STZ-induced diabetic rats was also carried out. The parameters such as the fasting blood glucose, hepatic glycogen content, and pancreatic antioxidant levels were monitored. In the acute study, the ethyl acetate fraction is the most potent in reducing the fasting serum glucose levels of the STZ-induced diabetic rats. The 14-day repeated oral administration of the ethyl acetate fraction significantly reduced the fasting blood glucose and pancreatic TBARS level and significantly increased the liver glycogen, pancreatic superoxide dismutase, and catalase activities as well as reduced glutathione levels. The histopathological studies during the subacute treatment have been shown to ameliorate the STZ-induced histological damage of pancreas. This paper concludes that the ethyl acetate fraction from ethanol extract of Stereospermum suaveolens possesses potent antihyperglycemic and antioxidant properties, thereby substantiating the use of plant in the indigenous system of medicine.

  20. Effect of Potent Ethyl Acetate Fraction of Stereospermum suaveolens Extract in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    T. Balasubramanian

    2012-01-01

    Full Text Available To evaluate the antihyperglycemic effect of ethyl acetate fraction of ethanol extract of Stereospermum suaveolens in streptozotocin-(STZ- induced diabetic rats by acute and subacute models. In this paper, various fractions of ethanol extract of Stereospermum suaveolens were prepared and their effects on blood glucose levels in STZ-induced diabetic rats were studied after a single oral administration (200?mg/kg. Administration of the ethyl acetate fraction at 200?mg/kg once daily for 14 days to STZ-induced diabetic rats was also carried out. The parameters such as the fasting blood glucose, hepatic glycogen content, and pancreatic antioxidant levels were monitored. In the acute study, the ethyl acetate fraction is the most potent in reducing the fasting serum glucose levels of the STZ-induced diabetic rats. The 14-day repeated oral administration of the ethyl acetate fraction significantly reduced the fasting blood glucose and pancreatic TBARS level and significantly increased the liver glycogen, pancreatic superoxide dismutase, and catalase activities as well as reduced glutathione levels. The histopathological studies during the subacute treatment have been shown to ameliorate the STZ-induced histological damage of pancreas. This paper concludes that the ethyl acetate fraction from ethanol extract of Stereospermum suaveolens possesses potent antihyperglycemic and antioxidant properties, thereby substantiating the use of plant in the indigenous system of medicine.

  1. Degradation of chlorimuron-ethyl by Aspergillus niger isolated from agricultural soil.

    Science.gov (United States)

    Sharma, Seema; Banerjee, Kaushik; Choudhury, Partha P

    2012-12-01

    Chlorimuron-ethyl, ethyl-2-[[[[(4-methoxy-6-chloro-pyrimidin-2-yl)amino]carbonyl]amino] sulfonyl]benzoate, is used as a pre- and postemergence herbicide for the control of important broadleaved weeds in soybean and maize. Due to its phytotoxicity to rotation crops, concerns regarding chlorimuron contamination of soil and water have been raised. Although it is degraded in the agricultural environment primarily via pH- and temperature-dependent chemical hydrolysis, microbial transformation also has an important role. Fungi such as Fusarium and Alternaria are unable to survive in artificial media containing chlorimuron-ethyl at 25 mg L(-1) . However, Aspergillus niger survived in minimal broth containing chlorimuron at 2 mg mL(-1) . Aspergillus niger degraded the herbicide to harvest energy through two major routes of degradation. One route involves the cleavage of the sulfonylurea bridge, resulting in the formation of two major metabolites, namely ethyl-2-aminosulfonylbenzoate (I) and 4-methoxy-6-chloro-2-amino-pyrimidine (II). The other route is the cleavage of sulfonylamide linkage, which generates the metabolite N-(4-methoxy-6-chloropyrimidin-2-yl) urea (III). Two other metabolites, saccharin (IV) and N-methyl saccharin (V), formed from metabolite II, were also identified. A metabolic pathway for the degradation of chlorimuron-ethyl by A. niger has been proposed. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  2. Associations of serum sex steroid hormones and 5α-androstane-3α,17β-diol glucuronide concentrations with prostate cancer risk among men treated with finasteride

    Science.gov (United States)

    Kristal, Alan R.; Till, Cathee; Tangen, Catherine M.; Goodman, Phyllis J.; Neuhouser, Marian L.; Stanczyk, Frank Z.; Chu, Lisa W.; Patel, Sherfaraz K.; Thompson, Ian; Reichardt, Juergen K.; Hoque, Ashraful; Platz, Elizabeth A.; Figg, William D.; Van Bokhoven, Adrie; Lippman, Scott M.; Hsing, Ann W

    2012-01-01

    BACKGROUND Finasteride, an inhibitor of 5 α-reductase (Type II), lowers intraprostatic dihydrotestosterone (DHT), which is reflected in serum as reduced 5α-androstane-3α,17β-diol glucuronide (3α-dG). It also modestly increases serum testosterone (T), estrone (E1) and estradiol (E2). In this altered hormonal milieu, it is unknown whether serum concentrations of these hormones are associated with prostate cancer risk. METHODS In this nested case-control study of men in the finasteride arm of the Prostate Cancer Prevention Trial, sex steroid hormones and sex hormone binding globulin (SHBG) were measured at baseline and approximately 3-years post-treatment in 553 prostate cancer cases and 694 controls. RESULTS Median post-treatment changes in concentrations of 3α-dG, T, E1, and E2 were −73.8%, +10.1%, +11.2%, and +7.5% (all pfinasteride-treated men, concentrations of 3α-dG were not associated with total or Gleason grades 2–6, 7–10 or 8–10 cancer. High serum estrogens may increase cancer risk when intraprostatic DHT is pharmacologically lowered. IMPACT Low post-treatment serum estrogens may identify men more likely to benefit from use of finasteride to prevent prostate cancer. PMID:22879203

  3. Novel one-pot process for the synthesis of ethyl 2-imino-4-methyl-2,3-dihydrothiazole-5-carboxylates

    Directory of Open Access Journals (Sweden)

    Beyzaei Hamid

    2015-01-01

    Full Text Available A facile one-pot two-step process for the synthesis of ethyl 2-imino-4-methyl-2,3-dihydrothiazole-5-carboxylates via the cyclocondensation of ethyl 2-thiocyanatoacetoacetate with a variety of hydrazine and hydrazide derivatives has been developed. Ethyl 2-thiocyanatoacetoacetate itself has been synthesized as intermediate from the reaction of ethyl 2-chloroacetoacetate with potassium thiocyanate (KSCN. The molecular structures of these newly synthesized compounds were elucidated on the basis of elemental analysis and spectral data.

  4. Experimental and modeling study of the thermal decomposition of C3-C5 ethyl esters behind reflected shock waves.

    Science.gov (United States)

    Ren, Wei; Spearrin, R Mitchell; Davidson, David F; Hanson, Ronald K

    2014-03-13

    The thermal decomposition of three ethyl esters, ethyl formate (C3H6O2), ethyl acetate (C4H8O2), and ethyl propanoate (C5H10O2), was studied behind reflected shock waves using laser absorption to measure concentration time-histories of H2O, CO2, and CO. Experimental conditions covered temperatures of 1301-1636 K, pressures of 1.48-1.72 atm, and reactant concentrations of 2000 ppm in argon. Recently developed mid-infrared laser diagnostics for H2O (2.5 μm), CO2 (4.3 μm), and CO (4.6 μm) provide orders-of-magnitude greater detectivity compared to previous near-infrared absorption sensors. The experimental results have highlighted significant differences among these three ethyl esters: negligible CO2 production during ethyl formate pyrolysis, quite slow CO formation rate during ethyl acetate pyrolysis, and nearly equal formation rate of H2O, CO2, and CO during ethyl propanoate pyrolysis. Detailed kinetic modeling was performed to understand the destruction pathways of these three ethyl esters with different alkyl chain lengths. Rate of production and sensitivity analyses were also carried out to interpret the experimental results and to identify the key reactions affecting experimental results.

  5. Aerobic oxidation of aqueous ethanol using heterogeneous gold catalysts: Efficient routes to acetic acid and ethyl acetate

    DEFF Research Database (Denmark)

    Jørgensen, Betina; Christiansen, Sofie Egholm; Thomsen, M.L.D.

    2007-01-01

    conditions, yields of 90-95% of acetic acid could be achieved at moderate temperatures and pressures. Based on our findings, a reaction pathway for the catalytic oxidation of ethanol via acetaldehyde to acetic acid is proposed, and the rate-determining step (RDS) in the mechanism is found to be the (possibly......The aerobic oxidation of aqueous ethanol to produce acetic acid and ethyl acetate was studied using heterogeneous gold catalysts. Comparing the performance of Au/MgAl2O4 and Au/TiO2 showed that these two catalysts exhibited similar performance in the reaction. By proper selection of the reaction...... oxygen-assisted) dehydrogenation of ethanol to produce acetaldehyde. It also is concluded that most of the CO2 formed as a byproduct in the reaction results from the absorbed intermediate in the dehydrogenation of ethanol to produce acetaldehyde. By varying the amount of water in the reaction mixture...

  6. Antimutagenic, antioxidant and free radical scavenging activity of ethyl acetate extracts from white, yellow and red onions.

    Science.gov (United States)

    Shon, Mi-Yae; Choi, Sang-Do; Kahng, Goon-Gjung; Nam, Sang-Hae; Sung, Nak-Ju

    2004-04-01

    The beneficial effects of red, yellow and white onion extracts have been assessed by antioxidant activity and antimutagenic activity. And the effects compared to BHT and ascorbic acid. Total phenolic compounds and flavonoids in onion extracts were determined. Yellow onion extract had more organic acid and free sugar than those detected in the white and red onion extract. The scavenging activity of DPPH radical and H(2)O(2) were increased depending on the concentration. The antioxidant activities using beta-carotene-linoleate system and reducing power were increased but the effect was small to that of BHT and ascorbic acid. After digested, extracts showed antimutagenic activities, and it seems that they inhibit the mutagenicity for digesting. This study demonstrated that the antimutagenicities and antioxidant properties of ethyl acetate extract against mutagens were related to their phenols and flavonoids, which are heat stable and losses digestive juices are relatively low.

  7. Crystal structure of ethyl (4R-2-amino-7-hydroxy-4-phenyl-4H-chromene-3-carboxylate

    Directory of Open Access Journals (Sweden)

    Joel T. Mague

    2015-07-01

    Full Text Available In the title compound, C18H17NO4, the dihedral angle between the phenyl ring and the fused six-membered ring is 77.65 (4°. The conformation of the molecule is determined in part by an intramolecular N—H...O hydrogen bond between the amino H atom and the carbonyl O atom, forming an S(6 motif. In the crystal, molecules are linked into N—H...O hydrogen-bonded inversion dimers which are then connected into chains along [001], forming a two-dimensional network parallel to (100 via O—H...O hydrogen bonds. C—H...O interactions further contribute to the crystal stability. The ethyl group is disordered over two sets of sites in a 0.801 (5:0.199 (5 ratio.

  8. Induction of neuronal damage in guinea pig brain by intratracheal infusion of 2-chloroethyl ethyl sulfide, a mustard gas analog.

    Science.gov (United States)

    Gadsden-Gray, Jessica; Mukherjee, Shyamali; Ogunkua, Olugbemiga; Das, Salil K

    2012-01-01

    Intratracheal infusion of 2-chloroethyl ethyl sulfide (CEES), a mustard gas analog and a chemical warfare agent is known to cause massive damage to lung. The purpose of this study was to determine whether intratracheal CEES infusion causes neuronal damage. Histological, immunohistochemical, and Western blot studies indicated that CEES treatment caused dose-dependent increases in blood cell aggregation, microglial cell number, microglial activation, and brain inflammation. In addition, an increased expression of α-synuclein and a decreased expression of the dopamine transporter were observed. The results indicate that intratracheal CEES infusion is associated with changes in brain morphology mediated by an increase in α-synuclein expression, leading to neurotoxicity in a guinea pig model. These changes may be mediated by oxidative stress. Furthermore, the present study indicates for the first time that intratracheal infusion of a single dose of CEES can cause neuroinflammation, which may lead to neurological disorders in later part of life. Copyright © 2011 Wiley Periodicals, Inc.

  9. Synthesis of iodine-123 labelled analogues of imidazenil and ethyl-imidazenil for studying benzodiazepine receptors using SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Katsifis, A.; Mattner, F.; Dikic, B.; Najdovski, L.; Kassiou, M. [Australian Nuclear Science and Technology Organisation, Menai, MSW (Australia). Radiopharmaceutical Div.

    1996-12-01

    The [{sup 123}I]iodinated analogues of the benzodiazepine receptor partial agonist imidazenil and N-ethyl imidazenil have been synthesised for the study of the central benzodiazepine receptor using SPECT. [{sup 123}I]Iodomidazenil and [{sup 123}I]N-ethyliodoimidazenil were prepared by nucleophilic bromine-iodine exchange in acetic acid at 150{sup o}. The products were purified by semi-preparative reverse-phase HPLC with average radiochemical yields of 80% in a total synthesis time of 80 minutes. The specific activity was determined to be greater than 2500 Ci/mmol. The radiochemical and chemical purity assessed by radio-TLC and HPLC were found to be 98%. Alternatively, iododestannylation reactions via the trimethyltin precursors with Na[{sup 123}I] in the presence of Chloramine-T or peracetic acid resulted in yields of only 20-25% with the bulk of activity being lost as volatile methyl [{sup 123}I]iodide. (author).

  10. AKTIVITAS ANTIHIPERURIKEMIA EKSTRAK ETIL ASETAT DAN ETANOL BUAH SALAK VARIETAS BONGKOK (Salacca edulis Reinw. PADA TIKUS GALUR WISTAR [Antihyperuricemic Activity of Ethyl Acetate and Ethanol Extracts of Snake Fruit var. Bongkok (Salacca edulis Reinw. on Wistar Rat

    Directory of Open Access Journals (Sweden)

    Leni Herliani Afrianti1*

    2011-06-01

    Full Text Available The aims of the study was to determine antihyperuricemic activity of ethyl acetate and ethanol extractsof snake fruit (Salacca edulis Reinw. var. Bongkok on Wistar male rats. Wistar male rats administered with 100 and 200 mg/kg b.w ethyl acetat extract and 200 mg/kg b.w ethanol extract and simulationsly induced with potassium oxonate peritoneally and uric acid orally showed descreased uric acid serum level significantly as compared to control group at 6th and 7thhour (p < 0.05. Meanwhile ethanol extract at 100 mg/kg bw did not affect uric acid serum level significantly. Determination of uric acid level in urine of the rats, indicated that administration ofethanol extract at 200 mg/kg bw, orprobenecid as a standard at 45 mg/kg bw, increased excretion of urine uric acid level significantly as compared to control group at 7thhour (p < 0.05. Additionally, administration of ethyl acetate extract at 100 and 200 mg/kg bw did not show an increase of uric acid excretion in urine. Mechanism of action of the ethyl acetate extract and ethanol extract as an antihyperuricemic agent has been proposed by inhibition of xanthine oxidase activity wich decrease the synthesis of uric acid. Hence, the mechanism of action of antihyperuricemia of the ethanol extract was suggested to be an uricosuric i.e. increases the excretion of urine uric acid and xanthine oxidase inhibitory.

  11. Direct Conversion of Cellulose into Ethyl Lactate in Supercritical Ethanol-Water Solutions.

    Science.gov (United States)

    Yang, Lisha; Yang, Xiaokun; Tian, Elli; Lin, Hongfei

    2016-01-08

    Biomass-derived ethyl lactate is a green solvent with a growing market as the replacement for petroleum-derived toxic organic solvents. Here we report, for the first time, the production of ethyl lactate directly from cellulose with the mesoporous Zr-SBA-15 silicate catalyst in a supercritical mixture of ethanol and water. The relatively strong Lewis and weak Brønsted acid sites on the catalyst, as well as the surface hydrophobicity, were beneficial to the reaction and led to synergy during consecutive reactions, such as depolymerization, retro-aldol condensation, and esterification. Under the optimum reaction conditions, ∼33 % yield of ethyl lactate was produced from cellulose with the Zr-SBA-15 catalyst at 260 °C in supercritical 95:5 (w/w) ethanol/water. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Microwave-assisted multicomponent diastereoselective 1,3-dipolar cycloaddition of ethyl glyoxylate derived azomethine ylides.

    Science.gov (United States)

    Mancebo-Aracil, Juan; Nájera, Carmen; Sansano, José M

    2013-01-28

    The thermal multicomponent 1,3-dipolar cycloaddition (1,3-DC) of diethyl aminomalonate or α-amino esters (derived from glycine, alanine, phenylalanine, and phenylglycine) with ethyl glyoxylate and the corresponding dipolarophile such as maleimides, methyl acrylate, methyl fumarate, (E)-1,2-bis(phenylsulfonyl)ethylene, and electron deficient alkynes allows the diastereoselective synthesis of new polysubstituted pyrrolidine derivatives. Microwave-assisted heating processes give better results than conventional heating ones, affording endo-cycloadducts as major stereoisomers. In general, 2,5-cis-cycloadducts are preferentially formed according to the previous formation of the W-shaped dipole. Only in the 1,3-DC of the disulfone with phenylglycine and ethyl glyoxylate the corresponding exo-trans-cycloadduct was isolated. The compound endo-cis-4b, derived from phenylalanine, ethyl glyoxylate and N-benzylmaleimide, has been further transformed into a very complex diazabicyclo[2.2.1]octane skeleton with potential biological activity.

  13. Reaction of 4-(7)-aminobenzimidazole with ethyl 2-alkylmalonates in 1, 2, 4-trichlorobenzene

    Energy Technology Data Exchange (ETDEWEB)

    Valle-Aguilera, Lucia E.; Gonzalez-Chavez, Marco M. [Universidad Autonoma de San Luis Potosi, San Luis Potosi (Mexico); Martinez, Roberto [Universidad Nacional Autonoma de Mexico, Mexico, D.F. (Mexico)

    1999-08-01

    The reaction of 4-(7)-aminobenzimidazole (2) with ethyl malonate or ethyl 2-allylmalonate, using 1, 2, 4-trichlorobenzene as the reaction solvent produces benzodiazepin-4, 6-diones and acetamidobenzimidazoles. However, reaction of (2) with ethyl 2-methylmalonate as well as the 2-butyl and 2-propyl derivatives, produced unknown dihydroxyquinolines in addition to benzodiazepin-4, 6-diones and acetamidobenzimidazoles. [Spanish] La reaccion del 4-(7)-aminobencimidazol (2) con malonato de etilo o 2-alilmalonato de etilo, utilizando el 1, 2, 4-triclorobenceno como disolvente, produce benzodiazepin-4,6-dionas y acetamido bencimidazoles. Sin embargo, la reaccion de (2) con el 2-metilmalonato de etilo, o con derivados de 2-propilo o 2-butilo, produce, ademas de compuestos similares a los anteriores, un tercer compuesto identificado como una dihidroxiquinolina.

  14. Crystal structure of the tetragonal polymorph of bis(1-ethyl-3-methylimidazolium tetrabromidocadmate

    Directory of Open Access Journals (Sweden)

    Tamara Đorđević

    2016-07-01

    Full Text Available Both unique Cd atoms in the tetragonal polymorph of bis(1-ethyl-3-methylimidazolium tetrabromidocadmate, (C6H11N22[CdBr4], occupy special positions (site symmetry -4. The crystal structure consists of isolated tetrahedral [CdBr4]2− anions which are surrounded by 1-ethyl-3-methylimidazolium cations. The methyl and ethyl side chains of the cations show positional disorder in a 0.590 (11:0.410 (11 ratio. In the crystal, (C6H11N2+ cations display three weak C—H...Br hydrogen-bond interactions through the imidazolium ring H atoms with the Br− ligands of the surrounding complex anions. The alkyl groups of the side chains are not involved in hydrogen bonding.

  15. Ethyl carbamate levels in wine and spirits from markets in Hebei Province, China.

    Science.gov (United States)

    Liu, Y P; Dong, B; Qin, Z S; Yang, N J; Lu, Y; Yang, L X; Chang, F Q; Wu, Y N

    2011-01-01

    Ethyl carbamate (EC) in wine, grain spirits and wine sauce (145 samples) was analysed using solid-phase extraction and stable isotope dilution GC/MS. Samples were obtained from markets in eight areas (Shijiazhuang, Baoding, Handan, Qinhuangdao, Langfang, Zhangjiakou, Xingtai and Cangzhou) of Hebei Province, China. The method had a limit of detection of 2 µg kg⁻¹, with recoveries varying from 95.7 to 102% and RSD ranging 2.3-5.6%. The average concentrations of ethyl carbamate in wines, grain spirits and wine sauce were 14.7 (<2.0-44.5) µg kg⁻¹, 33.8 (2.9-129) µg kg⁻¹ and 8.7 (<2.0-63.3) µg kg⁻¹, respectively. The results led to the development of limit standards that can be used to predict the concentration of ethyl carbamate in Chinese fermented wines.

  16. Characterization and Antioxidant Properties of Six Algerian Propolis Extracts: Ethyl Acetate Extracts Inhibit Myeloperoxidase Activity

    Directory of Open Access Journals (Sweden)

    Yasmina Mokhtaria Boufadi

    2014-02-01

    Full Text Available Because propolis contains many types of antioxidant compounds such as polyphenols and flavonoids, it can be useful in preventing oxidative damages. Ethyl acetate extracts of propolis from several Algerian regions show high activity by scavenging free radicals, preventing lipid peroxidation and inhibiting myeloperoxidase (MPO. By fractioning and assaying ethyl acetate extracts, it was observed that both polyphenols and flavonoids contribute to these activities. A correlation was observed between the polyphenol content and the MPO inhibition. However, it seems that kaempferol, a flavonoid, contributes mainly to the MPO inhibition. This molecule is in a high amount in the ethyl acetate extract and demonstrates the best efficiency towards the enzyme with an inhibiting concentration at 50% of 4 ± 2 µM.

  17. Extraction of medically interesting {sup 188}Re-perrhenate in methyl ethyl ketone for concentration purposes

    Energy Technology Data Exchange (ETDEWEB)

    Mushtaq, A. [Pakistan Inst. of Nuclear Science and Technology, Islamabad (Pakistan). Isotope Production Div.; Bukhari, T.H.; Khan, I.U. [Government College Univ., Lahore (Pakistan). Dept. of Chemistry

    2007-07-01

    The high bolus volumes (20-40mL) of the generator-produced Rhenium-188 require post elution concentration of the eluate for the preparation of a dissolved {beta}{sup -} source and radiopharmaceuticals labeled with Re-188 for radiotherapy. Solvent extraction of {sup 188}Re in methyl ethyl ketone was studied. With the increase of organic phase volume, extraction of {sup 188}Re was enhanced while mixing time of aqueous and organic phases did not show any significant effect on the extractability of {sup 188}Re in the organic phase. Almost 80% of {sup 188}Re was extracted in methyl ethyl ketone at a volume ratio of 1:2 for aqueous and organic phases. By evaporation/distillation of methyl ethyl ketone, {sup 188}Re was concentrated and dissolved in the desired volume of physiological saline. (orig.)

  18. Microalgae wet extraction using N-ethyl butylamine for fatty acid production

    Directory of Open Access Journals (Sweden)

    Ying Du

    2016-04-01

    Full Text Available Microalgae are considered a promising feedstock for the production of food ingredients, cosmetics, pharmaceutical products and biofuels. The energy intensity of drying and cell breaking of algae and solvent recovery afterwards hindered the route of algae biorefinery. In this work the influences of freeze drying and cell breaking to the extraction efficiency of crude lipid yield and fatty acid yield were investigated. Results showed that drying and cell breaking are not necessary for N-ethyl butylamine extraction, because good yields were obtained without. Crude lipid yield and fatty acid yield using N-ethyl butylamine were comparable with Bligh & Dyer extraction, making N-ethyl butylamine a candidate for further development of an energy efficient lipid extraction technology for non-broken microalgae. Keywords: Microalgae, Lipids, Extraction, Switchable solvent, Secondary amine

  19. [Ethyl chloride aerosol spray for local anesthesia before arterial puncture: randomized placebo-controlled trial].

    Science.gov (United States)

    Ballesteros-Peña, Sendoa; Fernández-Aedo, Irrintzi; Vallejo-De la Hoz, Gorka

    2017-06-01

    To compare the efficacy of an ethyl chloride aerosol spray to a placebo spray applied in the emergency department to the skin to reduce pain from arterial puncture for blood gas analysis. Single-blind, randomized placebo-controlled trial in an emergency department of Hospital de Basurto in Bilbao, Spain. We included 126 patients for whom arterial blood gas analysis had been ordered. They were randomly assigned to receive application of the experimental ethyl chloride spray (n=66) or a placebo aerosol spray of a solution of alcohol in water (n=60). The assigned spray was applied just before arterial puncture. The main outcome variable was pain intensity reported on an 11-point numeric rating scale. The median (interquartile range) pain level was 2 (1-5) in the experimental arm and 2 (1-4.5) in the placebo arm (P=.72). Topical application of an ethyl chloride spray did not reduce pain caused by arterial puncture.

  20. Mucor circinelloides whole-cells as a biocatalyst for the production of ethyl esters based on babassu oil.

    Science.gov (United States)

    Andrade, Grazielle S S; Carvalho, Ana K F; Romero, Cintia M; Oliveira, Pedro C; de Castro, Heizir F

    2014-12-01

    The intracellular lipase production by Mucor circinelloides URM 4182 was investigated through a step-by-step strategy to attain immobilized whole-cells with high lipase activity. Physicochemical parameters, such as carbon and nitrogen sources, inoculum size and aeration, were studied to determine the optimum conditions for both lipase production and immobilization in polyurethane support. Olive oil and soybean peptone were found to be the best carbon and nitrogen sources, respectively, to enhance the intracellular lipase activity. Low inoculum level and poor aeration rate also provided suitable conditions to attain high lipase activity (64.8 ± 0.8 U g(-1)). The transesterification activity of the immobilized whole- cells was assayed and optimal reaction conditions for the ethanolysis of babassu oil were determined by experimental design. Statistical analysis showed that M. circinelloides whole-cells were able to produce ethyl esters at all tested conditions, with the highest yield attained (98.1 %) at 35 °C using an 1:6 oil-to-ethanol molar ratio. The biocatalyst operational stability was also assayed in a continuous packed bed reactor (PBR) charged with glutaraldehyde (GA) and Aliquat-treated cells revealing half-life of 43.0 ± 0.5 and 20.0 ± 0.8 days, respectively. These results indicate the potential of immobilized M. circinelloides URM 4182 whole-cells as a low-cost alternative to conventional biocatalysts in the production of ethyl esters from babassu oil.

  1. Efeitos do trinexapac-ethyl sobre o crescimento e florescimento da grama-batatais Effects of trinexapac-ethyl on the growth and flowering of the bahiagrass

    Directory of Open Access Journals (Sweden)

    F.C.L. Freitas

    2002-12-01

    Full Text Available O objetivo deste trabalho foi avaliar a eficiência de doses do trinexapac-ethyl, bem como dos intervalos de aplicação após o corte no crescimento vegetativo e florescimento da grama-batatais (Paspalum notatum, na redução de cortes e na melhoria da qualidade do gramado. O ensaio foi conduzido no campus da Universidade Federal de Viçosa, em Viçosa-MG, entre os meses de dezembro de 1998 e março de 1999, em gramado estabelecido. O delineamento experimental foi o de blocos ao acaso, com 13 tratamentos e quatro repetições, distribuídos em esquema fatorial (6 x 2 + 1, com seis doses de trinexapac-ethyl (0,00; 0,25; 0,50; 0,75; 1,00; e 1,25 kg ha-1, aplicadas aos dois e cinco dias após o corte do gramado, e uma testemunha com cortes a cada três semanas. Foram efetuadas avaliações a três, seis, nove e doze semanas após o corte, para produção de biomassa seca total, altura e número de inflorescências. Verificou-se, para todas as características avaliadas, relação direta entre o aumento da dose do regulador de crescimento trinexapac-ethyl e o período de controle do crescimento vegetativo e do florescimento, evitando-se, com isso, cortes no gramado pelo período de até 12 semanas com a aplicação de 0,75 kg ha-1. Não se constatou efeito da época de aplicação e também de doses do trinexapac-ethyl sobre a coloração do gramado.The objective of this work was to evaluate the efficiency of doses and application intervals of trinexapac-ethyl on the vegetative growth and flowering of bahiagrass, to reduce clips and improve lawn quality. The experiment was conducted on the campus of the Federal University of Viçosa, in Viçosa-MG - Brazil, from December 1998 to March 1999, in an established lawn. The experiment was arranged in a randomized complete block design, with 13 treatments and four repetitions, distributed in a factorial scheme (6 x 2 + 1, with six doses of trinexapac-ethyl (0.00; 0.25; 0.50; 0.75; 1.00 and 1.25 kg ha-1

  2. EFEITO DO REGULADOR DE CRESCIMENTO TRINEXAPAC-ETHYL EM CULTIVARES DE ARROZ IRRIGADO

    OpenAIRE

    Ana Paula Estevo

    2013-01-01

    Este estudo tem por objetivo avaliar os efeitos do regulador de crescimento Trinexapac-ethyl sobre cultivares de arroz irrigado, verificando o efeito de doses crescentes do ingrediente ativo sobre a morfologia de plantas, sobre os componentes do rendimento e sobre a redução de acamamento de cultivar potencialmente acamadora. Neste sentido, dois ensaios foram realizados, um em campo, com o objetivo de avaliar os efeitos de doses e épocas de aplicação do Trinexapac-ethyl sobre os componentes do...

  3. Morphological characteristics of turf grasses in response to trinexapac-ethyl application

    OpenAIRE

    Costa, N.V.; Martins, D.; Rodella, R.A.; Rodrigues, A.C.P.; Cardoso, L.A.

    2009-01-01

    O presente trabalho teve como objetivo avaliar os efeitos da aplicação de duas doses de trinexapac-ethyl sobre a morfologia das espécies de gramas São Carlos (Axonopus compressus), Batatais (Paspalum notatum), Santo Agostinho (Stenotaphrum secundatum) e Esmeralda (Zoysia japonica). Os gramados foram cortados à altura de 3 cm no início do experimento e 20 dias depois. Após cada corte, foram realizadas duas aplicações sequenciais de trinexapac-ethyl nas doses de 56,5 + 56,5 e 113,0 + 113,0 g ha...

  4. Photostability of Isovaline and its Precursor 5-Ethyl-5-methylhydantoin Exposed to Simulated Space Radiations

    Directory of Open Access Journals (Sweden)

    Takeo Kaneko

    2012-01-01

    Full Text Available Aqueous solutions of isovaline and its precursor molecule, 5-ethyl-5-methylhydantoin, were irradiated with ultraviolet and γ-ray photons, to evaluate their structural stability against space radiation. The degree of photolysis was measured and irradiation products were identified using chiral, reversed-phase and ion-exchange high-performance liquid chromatography. The experimental results show that the degree of photolysis of 5-ethyl-5-methylhydantoin is more significant than that of isovaline under ultraviolet light irradiation, while the results under γ-ray irradiation are the opposite. As the products of isovaline photolysis, aspartic acid, serine, glutamic acid and alanine were dominantly detected.

  5. Effets de la toxicité des pesticides Maneb et Chlorpyrifos-Ethyl sur ...

    African Journals Online (AJOL)

    Dr Gatsing

    0,15 et 0,19 mg/l de Chlorpyrifos-Ethyl. Des corrélations (r = + 0,96 pour le Chlorpyrifos-Ethyl et r = + 0,98 pour le Maneb) ont été positives et fortes entre les taux de mortalité et les concentrations. La concentration létale 50% pendant 24 heures d'exposition (CL50-24h) a été relativement élevée avec le Maneb (1,93 mg/l) et.

  6. Telotristat ethyl in carcinoid syndrome: safety and efficacy in the TELECAST phase 3 trial.

    Science.gov (United States)

    Pavel, Marianne; Gross, David J; Benavent, Marta; Perros, Petros; Srirajaskanthan, Raj; Warner, Richard R P; Kulke, Matthew H; Anthony, Lowell B; Kunz, Pamela L; Hörsch, Dieter; Weickert, Martin O; Lapuerta, Pablo; Jiang, Wenjun; Kassler-Taub, Kenneth; Wason, Suman; Fleming, Rosanna; Fleming, Douglas; Garcia-Carbonero, Rocio

    2018-03-01

    Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing ≥4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a phase 3 companion study, assessed the safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea or elevated urinary 5-hydroxyindoleacetic acid (u5-HIAA)) with <4 BMs/day on SSAs (or ≥1 symptom or ≥4 BMs/day if not on SSAs) during a 12-week double-blind treatment period followed by a 36-week open-label extension (OLE). The primary safety and efficacy endpoints were incidence of treatment-emergent adverse events (TEAEs) and percent change from baseline in 24-h u5-HIAA at week 12. Patients ( N  = 76) were randomly assigned (1:1:1) to receive placebo or telotristat ethyl 250 mg or 500 mg 3 times per day (tid); 67 continued receiving telotristat ethyl 500 mg tid during the OLE. Through week 12, TEAEs were generally mild to moderate in severity; 5 (placebo), 1 (telotristat ethyl 250 mg) and 3 (telotristat ethyl 500 mg) patients experienced serious events, and the rate of TEAEs in the OLE was comparable. At week 12, significant reductions in u5-HIAA from baseline were observed, with Hodges-Lehmann estimators of median treatment differences from placebo of -54.0% (95% confidence limits, -85.0%, -25.1%, P  < 0.001) and -89.7% (95% confidence limits, -113.1%, -63.9%, P  < 0.001) for telotristat ethyl 250 mg and 500 mg. These results support the safety and efficacy of telotristat ethyl when added to SSAs in patients with CS diarrhea (ClinicalTrials.gov identifier: Nbib2063659). © 2018 The authors.

  7. Layered metal laurates as active catalysts in the methyl/ethyl esterification reactions of lauric acid

    Energy Technology Data Exchange (ETDEWEB)

    Lisboa, Fabio da Silva; Cordeiro, Claudiney S.; Wypych, Fernando, E-mail: wypych@ufpr.br [Centro de Pesquisas em Quimica Aplicada (CEPESQ), Departamento de Quimica, Universidade Federal do Parana, Curitiba, PR (Brazil); Gardolinski, Jose Eduardo F. da Costa [Laboratorio de Analise de Minerais e Rochas (LAMIR), Departamento de Geologia, Universidade Federal do Parana, Curitiba, PR (Brazil)

    2012-07-01

    In this work we report the synthesis, characterization and investigation of the catalytic activity of layered copper(II), manganese(II), lanthanum(III) and nickel(II) laurates in the methyl and ethyl esterification reactions of lauric acid. In the methyl esterification, conversions between 80 and 90% were observed for all catalysts, while for the ethyl esterification only manganese laurate showed reasonable catalytic activity, with conversions close to 75%. Reuse of copper and lanthanum laurates in three cycles of reaction was also investigated and both catalysts preserved the structure and retained catalytic activity close to that observed for the first reaction cycle. (author)

  8. Electron Impact Induced Reactions of Ethyl Acetate and Its Sulphur Analogues

    DEFF Research Database (Denmark)

    Egsgaard, Helge; Larsen, Elfinn; Carlsen, Lars

    1983-01-01

    The electron impact induced reactions of ethyl acetate and its sulphur analogues have been studied by application of collision activation mass spectrometry and isotopic labelling with H-2 and O-18. The [M-C2H4]+·, [M-CH3]+ and [M-H2O]+· were selected for detailed investigations.......The electron impact induced reactions of ethyl acetate and its sulphur analogues have been studied by application of collision activation mass spectrometry and isotopic labelling with H-2 and O-18. The [M-C2H4]+·, [M-CH3]+ and [M-H2O]+· were selected for detailed investigations....

  9. X-ray photoelectron spectroscopy and infra-red studies of x-ray-induced beam damage of cellulose, ethyl cellulose and ethyl-hydroxyethyl cellulose

    Energy Technology Data Exchange (ETDEWEB)

    Brown, N.M.D.; Hewitt, J.A.; Meenan, B.J. (Ulster Univ., Coleraine (United Kingdom))

    1992-03-01

    The cellulose derivatives ethyl cellulose and ethyl-hydroxyethyl cellulose (EHEC) have been studied by XPS in the form of solvent-cast films. All the films, as well as a sample of cellulose used as a standard material, show significant surface degradation on irradiation in the time period consistent with XPS data acquisition. Under the experimental conditions employed here the four materials studied behave similarly, in that a reaction occurs in the cellulose skeleton, resulting in dehydroxylation of some of the pyranose units in the surface layers, with concomitant elimination of molecules of water. An infrared (IR) analysis of the ethyl cellulose and high-molecular-weight EHEC films indicates the presence of a strong carbonyl band, no evidence for which is found in the XPS spectra. However, other features of the IR spectra support the proposed dehydroxylation mechanism. The origin of this inconsistency is unclear but may be attributable to either differences in the surface and bulk degradation products formed or to the detection differences of the XPS and IR techniques. (author).

  10. Attenuation of Methotrexate-Induced Embryotoxicity and Oxidative Stress by Ethyl Pyruvate

    Directory of Open Access Journals (Sweden)

    Najafi Gholamreza

    2016-07-01

    Full Text Available Background Methotrexate (MTX, as an anti-folate agent, is widely used in the treatment of rheumatic disorders and malignant tumors, however it damages reproductive sys- tem in mice. The aim of this research was to study the effects of ethyl pyruvate (EP on embryo development and oxidative stress changes in the testis of mice treated with MTX. Materials and Methods In this experimental study, thirty-two adult male Naval Medical Research Institute mice, with average weight of 26 ± 2 g, were divided into four groups. The first group (control received distilled water (0.1 ml/mice/day, while the second group was intraperitoneally (IP treated with 20 mg/kg MTX once per week. The third group was IP treated with 40 mg/kg/day EP, and the fourth group was IP treated with both 20 mg/kg MTX and 40 mg/kg/day EP for 30 days. At the end of treatment fertilization rate and embryonic development were evaluated. Differences between these groups were assessed by ANOVA using the SPSS software package for Windows with a Tukey-Kramer multiple post-hoc comparison test. Results MTX treatment caused significant (P<0.05 increase in malondialdehyde (MDA and reduced catalase (CAT, as well as leading to in vitro fertilization (IVF and embryonic development. The improved effects of EP on the IVF were determined by the reduced level of MDA (index of oxidative stress and significant increased level of CAT (a key antioxidant. We observed significant increase in fertilization rate and embryonic development in the treated group with both MTX and EP. Conclusion It is suggested that EP can be useful in ameliorating testicular damages and embryotoxicity induced by MTX. These effects could be attributed to its antioxidant properties.

  11. Synthesis of 10-Ethyl Flavin: A Multistep Synthesis Organic Chemistry Laboratory Experiment for Upper-Division Undergraduate Students

    Science.gov (United States)

    Sichula, Vincent A.

    2015-01-01

    A multistep synthesis of 10-ethyl flavin was developed as an organic chemistry laboratory experiment for upper-division undergraduate students. Students synthesize 10-ethyl flavin as a bright yellow solid via a five-step sequence. The experiment introduces students to various hands-on experimental organic synthetic techniques, such as column…

  12. 21 CFR 172.225 - Methyl and ethyl esters of fatty acids produced from edible fats and oils.

    Science.gov (United States)

    2010-04-01

    ... from edible fats and oils. 172.225 Section 172.225 Food and Drugs FOOD AND DRUG ADMINISTRATION... Methyl and ethyl esters of fatty acids produced from edible fats and oils. Methyl esters and ethyl esters of fatty acids produced from edible fats and oils may be safely used in food, subject to the...

  13. 21 CFR 176.160 - Chromium (Cr III) complex of N-ethyl-N-heptadecylfluoro-octane sulfonyl glycine.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Chromium (Cr III) complex of N-ethyl-N... § 176.160 Chromium (Cr III) complex of N-ethyl-N-heptadecylfluoro-octane sulfonyl glycine. The chromium... by weight of the chromium (Cr III) complex of heptadecylfluoro-octane sulfonic acid may be safely...

  14. Microbial community dynamics during the bioremediation process of chlorimuron-ethyl-contaminated soil by Hansschlegelia sp. strain CHL1.

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    Liqiang Yang

    Full Text Available Long-term and excessive application of chlorimuron-ethyl has led to a series of environmental problems. Strain Hansschlegelia sp. CHL1, a highly efficient chlorimuron-ethyl degrading bacterium isolated in our previous study, was employed in the current soil bioremediation study. The residues of chlorimuron-ethyl in soils were detected, and the changes of soil microbial communities were investigated by phospholipid fatty acid (PLFA analysis. The results showed that strain CHL1 exhibited significant chlorimuron-ethyl degradation ability at wide range of concentrations between 10μg kg-1 and 1000μg kg-1. High concentrations of chlorimuron-ethyl significantly decreased the total concentration of PLFAs and the Shannon-Wiener indices and increased the stress level of microbes in soils. The inoculation with strain CHL1, however, reduced the inhibition on soil microbes caused by chlorimuron-ethyl. The results demonstrated that strain CHL1 is effective in the remediation of chlorimuron-ethyl-contaminated soil, and has the potential to remediate chlorimuron-ethyl contaminated soils in situ.

  15. Multicomponent Synthesis of a N-Protected Alpha-Amino Ester: Ethyl 2-((4-Methoxyphenyl)Amino)-3-Phenylpropanoate

    Science.gov (United States)

    Le Gall, Erwan; Pignon, Antoine

    2012-01-01

    This laboratory experiment describes the preparation of a N-protected phenylalanine ethyl ester by a zinc-mediated Mannich-like multicomponent reaction between benzyl bromide, "p"-anisidine, and ethyl glyoxylate. The one-step reaction involves the in situ metallation of benzyl bromide into a benzylzinc reagent and its addition onto imine (Barbier…

  16. [Role of mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) in the obtaining of stabilized magnetite nanoparticles for biomedical application].

    Science.gov (United States)

    Vazhnichaya, Ye M; Mokliak, Ye V; Kurapov, Yu A; Zabozlaev, A A

    2015-01-01

    Magnetite nanoparticles (NPs) are studied as agents for magnetic resonance imaging, hyperthermia of malignant tumors, targeted drug delivery as well as anti-anemic action. One of the main problems of such NPs is their aggregation that requires creation of methods for magnetite NPs stabilization during preparation of liquid medicinal forms on their basis. The present work is devoted to the possibility of mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) use for solubilization of magnetite NPs in hydrophilic medium. For this purpose, the condensate produced by electron-beam evaporation and condensation, with magnetite particles of size 5-8 nm deposited into the crystals of sodium chloride were used in conjunction with substance of mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate), and low molecular weight polyvinylpyrrolidone (PVP). The NP condensate was dispersed in distilled water or PVP or mexidol solutions. NPs size distribution in the liquid phase of the systems was determined by photon correlation spectroscopy, iron (Fe) concentration was evaluated by atomic emission spectrometry. It is shown that in the dispersion prepared in distilled water, the major amount of NPs was of 13-120 nm in size, in mexidol solution - 270-1700 nm, in PVP solution - 30-900 nm. In the fluid containing magnetite NPs together with mexidol and PVP, the main fraction (99.9%) was characterized by the NPs size of 14-75 nm with maximum of 25 nm. This system had the highest iron concentration: it was similar to that in the sample with mexidol solution and 6.6-7.3 times higher than the concentration in the samples with distilled water or PVP. Thus, in the preparation of aqueous dispersions based on magnetite NPs condensate, mexidol provides a transition of Fe to the liquid phase in amount necessary to achieve its biological activity, and PVP stabilizes such modified NPs.

  17. Evaluation of the diagnostic potential of urinary N-Acetyltyramine-O,β-glucuronide (NATOG) as diagnostic biomarker for Onchocerca volvulus infection.

    Science.gov (United States)

    Lagatie, Ole; Njumbe Ediage, Emmanuel; Batsa Debrah, Linda; Diels, Luc; Nolten, Christ; Vinken, Petra; Debrah, Alex; Dillen, Lieve; Silber, Steven; Stuyver, Lieven J

    2016-05-23

    Onchocerciasis, also known as river blindness is one of the neglected tropical diseases affecting millions of people, mainly in sub-Saharan Africa and is caused by the filarial nematode Onchocerca volvulus. Efforts to eliminate this disease are ongoing and are based on mass drug administration programs with the microfilaricide ivermectin. In order to monitor the efficacy of these programs, there is an unmet need for diagnostic tools capable of identifying infected patients. We have investigated the diagnostic potential of urinary N-acetyltyramine-O,β-glucuronide (NATOG), which is a promising O. volvulus specific biomarker previously identified by urine metabolome analysis. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was used to assess the stability characteristics of NATOG and to evaluate the levels of NATOG in study samples. An LC-fluorescence method was also developed. Stability characteristics of NATOG were investigated and shown to be ideally suited for use in tropical settings. Also, an easy and more accessible method based on liquid chromatography coupled to fluorescence detection was developed and shown to have the necessary sensitivity (limit of quantification 1 μM). Furthermore, we have evaluated the levels of NATOG in a population of 98 nodule-positive individuals from Ghana with no or low levels of microfilaria in the skin and compared them with the levels observed in different control groups (endemic controls (n = 50), non-endemic controls (n = 18) and lymphatic filariasis (n = 51). Only a few (5 %) of nodule-positive individuals showed an increased level (> 10 μM) of NATOG and there was no statistical difference between the nodule-positive individuals and the control groups (P > 0.05). Results of the present study indicate the limited potential of NATOG as a diagnostic biomarker for O. volvulus infection in amicrofilaridermic individuals.

  18. Modelling of the blood-brain barrier transport of morphine-3-glucuronide studied using microdialysis in the rat: involvement of probenecid-sensitive transport

    Science.gov (United States)

    Xie, Rujia; Bouw, M René; Hammarlund-Udenaes, Margareta

    2000-01-01

    The objective of this study was to investigate the impact of probenecid on the blood-brain barrier (BBB) transport of morphine-3-glucuronide (M3G). Two groups of rats received an exponential infusion of M3G over 4 h to reach a target plasma concentration of 65 μM on two consecutive days. Probenecid was co-administered in the treatment group on day 2. Microdialysis was used to estimate unbound M3G concentrations in brain extracellular fluid (ECF) and blood. In vivo recovery of M3G was calculated with retrodialysis by drug, preceding the drug administration. The BBB transport was modelled using NONMEM. In the probenecid group, the ratio of the steady-state concentration of unbound M3G in brain ECF to that in blood was 0.08±0.02 in the absence and 0.16±0.05 in the presence of probenecid (P=0.001). In the control group, no significant difference was found in this ratio between the 2 days (0.11±0.05 and 0.10±0.02, respectively). The process that appears to be mainly influenced by probenecid is influx clearance into the brain (0.11 μl min−1 g-brain−1 vs 0.17 μl min−1 g-brain−1, in the absence vs presence of probenecid, Pprobenecid. In conclusion, a probenecid-sensitive transport system is involved in the transport of M3G across the BBB. PMID:11139459

  19. Inhibition of P-glycoprotein and multidrug resistance-associated protein 2 regulates the hepatobiliary excretion and plasma exposure of thienorphine and its glucuronide conjugate

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    Ling-Lei Kong

    2016-08-01

    Full Text Available Thienorphine (TNP is a novel partial opioid agonist that has completed phase II clinical evaluation as a promising drug candidate for the treatment of opioid dependence. Previous studies have shown that TNP and its glucuronide conjugate (TNP-G undergo significant bile excretion. The purpose of this study was to investigate the roles of efflux transporters in regulating biliary excretion and plasma exposure of TNP and TNP-G. An ATPase assay suggested that TNP and TNP-G were substrates of P-gp and MRP2, respectively. The in vitro data from rat hepatocytes showed that bile excretion of TNP and TNP-G was regulated by the P-gp and MRP2 modulators. The accumulation of TNP and TNP-G in HepG2 cells significantly increased by the treatment of mdr1a or MRP2 siRNA for P-gp or MRP2 modulation. In intact rats, the bile excretion and pharmacokinetic profiles of TNP and TNP-G were remarkably changed with tariquidar and probenecid pretreatment, respectively. Tariquidar increased the Cmax and AUC0-t and decreased MRT and T1/2 of TNP, whereas probenecid decreased the plasma exposure of TNP-G and increased its T1/2. Knockdown P-gp and MRP2 function using siRNA significantly increased the plasma exposure of TNP and TNP-G and reduced their mean retention time in mice. These results indicated the important roles of P-gp and MRP2 in hepatobiliary excretion and plasma exposure of TNP and TNP-G. Inhibition of the efflux transporters may affect the pharmacokinetics of TNP and result in a drug-drug interaction between TNP and the concomitant transporter inhibitor or inducer in clinic.

  20. Uridine diphosphate glucuronide transferase 1A1FNx0128 gene polymorphism and the toxicity of irinotecan in recurrent and refractory small cell lung cancer

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    Fan Yun

    2014-01-01

    Full Text Available Objective: The aim was to investigate the association between uridine diphosphate glucuronide transferase 1A1 (UGT1A1 gene promoter region polymorphism and irinotecan-related adverse effects and efficacy on recurrent and refractory small cell lung cancer (SCLC. Materials and Methods: A total of 31 patients with recurrent and refractory SCLC were enrolled in this study from June 2012 to August 2013 and received at least two cycles of single-agent irinotecan chemotherapy. The efficacy and adverse effects of irinotecan were evaluated. DNA was extracted from peripheral blood and direct sequencing method was employed to test UGT1A1FNx0128 polymorphism, thus analyzing the correlation between UGT1A1FNx0128 polymorphism and irinotecan-related side-effects and efficacy. Results: A total of 25 cases (80.6% were UGT1A1FNx0128 wild-type (TA 6 /(TA 6 ; 6 cases (19.4% were heterozygous mutant (TA 6 /(TA 7 , no homozygous mutant genotype (TA 7 /(TA 7 was found. The incidences of grade 3/4 neutropenia, diarrhea and thrombocytopenia were 35.5%, 25.8% and 22.6% in all the patients, respectively. The incidence of 3/4 adverse effects in patients with genotype (TA 6 /(TA 6 and heterozygous (TA 6 /(TA 7 had no statistical difference (P > 0.05 for all. The overall response rate (ORR was 32.3%. Median progression free survival (PFS and overall survival (OS were 4 months and 7.5 months in all patients, respectively. There was no statistical difference in ORR, PFS and OS between genotype (TA 6 /(TA 6 patients and heterozygous (TA 6 /(TA 7 patients. Conclusion: Irinotecan showed efficacy in patients with recurrent and refractory SCLC; UGT1A1 FNx01 28 polymorphism failed to predict the incidence of serious adverse effects and efficacy of irinotecan.