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Sample records for plasma pharmacokinetic parameters

  1. [Dalbavancin: pharmacokinetic and pharmacodynamic parameters].

    Science.gov (United States)

    Azanza, José Ramón; Sádaba, Belén; Reis, Joana

    2017-01-01

    Dalbavancin is a new lipoglycopeptide antibiotic whose structure influences its pharmacokinetic profile. It is not absorbed after oral administration and is therefore administered intravenously. It is distributed through intracellular fluid, reaching adequate concentrations in the skin, bone, blister fluid and synovial fluid. Plasma protein binding is very high. Concentrations in brain tissue and cerebrospinal fluid (CSF) are inadequate. Excretion is through non-microsomal metabolism with inactive metabolites and through the kidneys by glomerular filtration. Dalbavancin is eliminated slowly, as shown by its clearance value and its terminal elimination half-life, which exceeds 300 hours. This means that adequate concentrations of the drug remain in plasma and tissues for a prolonged period and explains the dosing regimen: a first dose of 1g followed 7 days later by a 500mg dose. The pharmacokinetics are linear and show little intra- and interindividual variability. There are no pharmacokinetic interactions. Dose adjustment is not required for patients with mild or moderate renal insufficiency (creatinine clearance ≥ 30 to 79ml/min). Dosage adjustment is not required in patients regularly receiving elective haemodialysis (3 times/week) and the drug can be administered without consideration of haemodialysis times. In patients with chronic renal insufficiency, whose creatinine clearance is < 30ml/min and who are not regularly receiving elective haemodialysis, the recommended dose should be reduced to 750mg per week, followed 1 week later by 375mg. Dosage adjustment does not seem necessary in patients with liver failure or in older patients. There is no information on the most appropriate dosage in children. The pharmacokinetic/pharmacodynamics parameter that best describes the effectiveness of dalbavancin is the ratio between the area under the curve and the minimum inhibitory concentration.

  2. Buprenorphine pharmacokinetic parameters during coronary artery bypass graft surgery.

    Science.gov (United States)

    Amani, A; Joseph, T; Balasaraswathi, K

    1997-10-01

    The pharmacokinetic parameters of buprenorphine (BN) after a single bolus dose of 10 microg/kg i.v. was investigated in 6 male patients whose age averaged 59+/-9.8 years and body weight of 65.8+/-5.7 kg undergoing coronary artery bypass graft surgery (CABG). The unbound BN plasma concentrations were detected using ultrafiltration and high performance liquid chromatography/electro-chemical detection (HPLC/ECD) method. During cardiopulmonary bypass (CPB) there was a fall in BN plasma concentrations, observations similar to reports on fentanyl, sufentanil and alfentanil. This is probably due to haemodilution, hypothermia and hydrophobic sequestration of drug on to the CPB tubing. After CPB the concentrations rose to values higher than during CPB, though it did not attain pre CPB concentrations. These variations were not statistically significant indicating that plasma levels were adequately stable during CPB. The plasma concentration time curves were biexponential and the pharmacokinetic parameters obtained were : distribution half-life 37.24+/-6.57 min, elimination half-life 482.69+/-79 min, clearance 1221.97+/-209.42 ml/min, and volume of distribution 736.46+/-71.25 L. BN in the dose used follows the pharmacokinetic pattern of other commonly used narcotics during CABG. The mean +/- SEM plasma BN concentration during CPB was 0.51+/-0.03 ng/ml which was adequate for the maintenance of analgesia and anaesthesia, as none of our patients expressed the signs and symptoms of awareness during surgery. Further, unlike the other narcotics muscle rigidity was absent. Thus BN is a safe and good alternative to other narcotics for patients undergoing CABG.

  3. Pharmacokinetic behaviors and oral bioavailability of oridonin in rat plasma

    Institute of Scientific and Technical Information of China (English)

    Wen XU; Jin SUN; Ting-ting ZHANG; Bo MA; Sheng-miao GUI; Da-wei CHEN; Zhong-gui HE

    2006-01-01

    Aim: To study the intravenous and oral pharmacokinetic behavior of oridonin and its extent of absolute oral bioavailability in rats. Methods: Oridonin was administered to rats via iv (5,10 and 15 mg/kg), po (20,40 and 80 mg/kg) or ip administration (10 mg/kg). The concentrations of oridonin in rat plasma were determined by a high performance liquid chromatography with electrospray ionization mass spec-trometric detection (HPLC/ESI-MS) method and the pharmacokinetic parameters were determined by non-compartmental analysis. Results: The plasma concentration of oridonin after intravenous administration decreased poly exponentially, and the pharmacokinetic parameters of oridonin were dose-independent within the examined range. Oridonin was absorbed rapidly after oral gavage with a pharmacokinetics were observed for oridonin within the range of iv doses, while the extent of absolute oral bioavailability was rather low and dose-dependent. The low and dose-dependent extent of oral bioavailability may be due to the saturation of first-pass effects.

  4. Influence of Differing Analgesic Formulations of Aspirin on Pharmacokinetic Parameters

    Directory of Open Access Journals (Sweden)

    Kunal Kanani

    2015-08-01

    Full Text Available Aspirin has been used therapeutically for over 100 years. As the originator and an important marketer of aspirin-containing products, Bayer’s clinical trial database contains numerous reports of the pharmacokinetics of various aspirin formulations. These include evaluations of plain tablets, effervescent tablets, granules, chewable tablets, and fast-release tablets. This publication seeks to expand upon the available pharmacokinetic information concerning aspirin formulations. In the pre-systemic circulation, acetylsalicylic acid (ASA is rapidly converted into its main active metabolite, salicylic acid (SA. Therefore, both substances are measured in plasma and reported in the results. The 500 mg strength of each formulation was chosen for analysis as this is the most commonly used for analgesia. A total of 22 studies were included in the analysis. All formulations of 500 mg aspirin result in comparable plasma exposure to ASA and SA as evidenced by AUC. Tablets and dry granules provide a consistently lower Cmax compared to effervescent, granules in suspension and fast release tablets. Effervescent tablets, fast release tablets, and granules in suspension provide a consistently lower median Tmax compared to dry granules and tablets for both ASA and SA. This report reinforces the importance of formulation differences and their impact on pharmacokinetic parameters.

  5. Pharmacokinetic Comparison of Soy Isoflavone Extracts in Human Plasma.

    Science.gov (United States)

    Rodríguez-Morató, Jose; Farré, Magí; Pérez-Mañá, Clara; Papaseit, Esther; Martínez-Riera, Roser; de la Torre, Rafael; Pizarro, Nieves

    2015-08-12

    The soy isoflavones daidzein and genistein produce several biological activities related to health benefits. A number of isoflavone extracts are commercially available, but there is little information concerning the specific isoflavone content of these products or differences in their bioavailability and pharmacokinetics. This study describes the development and validation of an analytical method to detect and quantify daidzein, genistein, and equol in human plasma using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The method was applied in a crossover, randomized, bioavailability study. Twelve healthy volunteers were administered the same total isoflavones dose from two isoflavone supplement preparations (Super-Absorbable Soy Isoflavones (Life Extension, USA) and Fitoladius (Merck, Spain)). The pharmacokinetic parameters (AUC0-24/dose and Cmax/dose) of the isoflavones from the two preparations differed significantly. Such differences in bioavailability and kinetics may have relevant effects on the health benefits derived from their intake.

  6. [The main pharmacokinetic parameters of p-tyrosol upon intravenous injection in rats. II. Verification of the pharmacokinetics linearity and evaluation of the possible accumulation].

    Science.gov (United States)

    Chernysheva, G A; Plotnikov, M B; Smol'iakova, V I; Cherkashina, I V; Tolstikova, T G; Krysin, A P; Sorokina, I V

    2006-01-01

    The main pharmacokinetic parameters of p-tyrosol after single (in 3 doses) and repeated intravenous injection were studied in rats. The content ofp-tyrosol in the blood plasma was determined by spectrofluorimetric method. The pharmacokinetic parameters of p-tyrosol are linear in the dose range from 50 to 200 mg/kg. Repeated administration leads to accelerated metabolic elimination of p-tyrosol.

  7. Low dose lopinavir/ritonavir tablet achieves adequate pharmacokinetic parameters in HIV-infected Thai adolescents.

    NARCIS (Netherlands)

    Klinklom, A.; Puthanakit, T.; Gorowara, M.; Phasomsap, C.; Kerr, S.; Sriheara, C.; Ananworanich, J.; Burger, D.M.; Ruxrungtham, K.; Pancharoen, C.

    2012-01-01

    BACKGROUND: Lopinavir/ritonavir (LPV/r) is an effective and commonly used protease inhibitor in HIV-infected adolescents. Previous data showed high plasma concentrations of LPV in Thai patients. This study determined the pharmacokinetic (PK) parameters of a low-dose LPV/r tablet (70% of standard dos

  8. Relationship between pharmacokinetics of 5-FU in plasma and in saliva, and toxicity of 5-fluorouracil/folinic acid

    NARCIS (Netherlands)

    Jansman, FGA; Coenen, JLLM; De Graaf, JC; Tobi, H; Sleijfer, DT; Brouwers, JRBJ

    2002-01-01

    Background: Dose adaptation based on pharmacokinetic parameters has been shown to decrease toxicity of some 5-fluorouracil(5-FU)-based continuous infusion regimens. Patients and Methods: In the present study the relationship between 5-FU pharmacokinetics in plasma and in saliva, and toxicity was inv

  9. [Diagnostic value of quantitative pharmacokinetic parameters and relative quantitative pharmacokinetic parameters in breast lesions with dynamic contrast-enhanced MRI].

    Science.gov (United States)

    Sun, T T; Liu, W H; Zhang, Y Q; Li, L H; Wang, R; Ye, Y Y

    2017-08-01

    Objective: To explore the differential between the value of dynamic contrast-enhanced MRI quantitative pharmacokinetic parameters and relative pharmacokinetic quantitative parameters in breast lesions. Methods: Retrospective analysis of 255 patients(262 breast lesions) who was obtained by clinical palpation , ultrasound or full-field digital mammography , and then all lessions were pathologically confirmed in Zhongda Hospital, Southeast University from May 2012 to May 2016. A 3.0 T MRI scanner was used to obtain the quantitative MR pharmacokinetic parameters: volume transfer constant (K(trans)), exchange rate constant (k(ep))and extravascular extracellular volume fraction (V(e)). And measured the quantitative pharmacokinetic parameters of normal glands tissues which on the same side of the same level of the lesions; and then calculated the value of relative pharmacokinetic parameters: rK(rans)、rk(ep) and rV(e).To explore the diagnostic value of two pharmacokinetic parameters in differential diagnosis of benign and malignant breast lesions using receiver operating curves and model of logistic regression. Results: (1)There were significant differences between benign lesions and malignant lesions in K(trans) and k(ep) (t=15.489, 15.022, respectively, P0.05). The areas under the ROC curve(AUC)of K(trans), k(ep) and V(e) between malignant and benign lesions were 0.933, 0.948 and 0.387, the sensitivity of K(trans), k(ep) and V(e) were 77.1%, 85.0%, 51.0% , and the specificity of K(trans), k(ep) and V(e) were 96.3%, 93.6%, 60.8% for the differential diagnosis of breast lesions if taken the maximum Youden's index as cut-off. (2)There were significant differences between benign lesions and malignant lesions in rK(trans), rk(ep) and rV(e) (t=14.177, 11.726, 2.477, respectively, Pquantitative pharmacokinetic parameters and the prediction probability of relative quantitative pharmacokinetic parameters(Z=0.867, P=0.195). Conclusion: There was no significant difference between

  10. Study on pharmacokinetics of Amygdalin after oral administration of semen persicae extraction in rat plasma by HPLC

    OpenAIRE

    Zhang, Zhidan; Gao, Wenyuan; Ma, Chaoyi; Liu, Changxiao

    2011-01-01

    Semen Persicae was a traditional Chinese medicine for the treatment of diseases such as inflammation and hyperlipemia. Amygdalin was one of the main active ingredients of this traditional Chinese medicine. In this paper, pharmacokinetic study was conducted to obtain pharmacokinetic parameters of amygadalin after oral administration of Semen Persicae extraction in rat plasma. HPLC-UV was used to determine the concentration of amygdalin in rat plasma at different time points after administratio...

  11. Pharmacokinetic parameters of meloxicam after its oral administration in goat

    Directory of Open Access Journals (Sweden)

    A R. Wani

    2014-03-01

    Full Text Available Aim: The objective of the present study was to find out the levels of analgesic drug meloxicam in the blood plasma of young goats. The drug was given to them through oral route. Data was used to elucidate the Pharmacokinetic determinants of the drug which were employed to arrive at the dose schedule and frequency of the drug in goats. Materials and Methods: Elaborate pharmacokinetic research of the drug meloxicam was done on 18 to 24 months old, five adult male local goats (Capra hircus of Assam weighing 20 to 25 kg.The drug was given orally at the dose rate of 0.35 mg/kg at the Goat Rearing farm, Guwahati, Assam. Analysis of blood was done by high performance liquid chromatography (HPLC system. Results: The mean values of area under curve (AUC and mean area under curve (AUMC were 3137.488 ± 125.3749 µg.min/ml and 4650460 ± 380892.4744 µg.min2/ml respectively .The mean peak plasma level of meloxicam was 1.972 ± 0.0477 µg/ml at 600 min. The mean values of elimination half life (t1/2β and absorption half life (t1/2Ka were 693±0.00 min and 170.6 ± 17.0076 min respectively. The mean values of volume of distribution (Vd and mean residence time (MRT were 0.114 ± 0.0156 L/kg and 1472.264 ± 63.336 min respectively. The mean value of Tmax was found to be 497 ± 19.8040 min. Following single oral administration the minimum effective therapeutic concentration or minimum effective plasma concentration of meloxicam was detectable up to 1200 min. The bioavailibity (F of the drug was 80.5 ± 10.0150%. Conclusion: These pharmacokinetic determinants were used to determine the frequency and dose schedule of meloxicam in goats. The minimum effective concentration of the drug is 0.7 µg/ml in plasma. To maintain this, an initial loading dose of 0.5 mg/kg body weight should be followed by a maintenance dose of 0.4 mg/kg body weight/10 hour.

  12. Elucidating the Plasma and Liver Pharmacokinetics of Simeprevir in Special Populations Using Physiologically Based Pharmacokinetic Modelling.

    Science.gov (United States)

    Snoeys, Jan; Beumont, Maria; Monshouwer, Mario; Ouwerkerk-Mahadevan, Sivi

    2016-11-29

    The disposition of simeprevir (SMV) in humans is characterised by cytochrome P450 3A4 metabolism and hepatic uptake by organic anion transporting polypeptide 1B1/3 (OATP1B1/3). This study was designed to investigate SMV plasma and liver exposure upon oral administration in subjects infected with hepatitis C virus (HCV), in subjects of Japanese or Chinese origin, subjects with organ impairment and subjects with OATP genetic polymorphisms, using physiologically based pharmacokinetic modelling. Simulations showed that compared with healthy Caucasian subjects, SMV plasma exposure was 2.4-, 1.7-, 2.2- and 2.0-fold higher, respectively, in HCV-infected Caucasian subjects, in healthy Japanese, healthy Chinese and subjects with severe renal impairment. Further simulations showed that compared with HCV-infected Caucasian subjects, SMV plasma exposure was 1.6-fold higher in HCV-infected Japanese subjects. In subjects with OATP1B1 genetic polymorphisms, no noteworthy changes in SMV pharmacokinetics were observed. Simulations suggested that liver concentrations in Caucasians with HCV are 18 times higher than plasma concentrations.

  13. Plasma diagnostics discharge parameters and chemistry

    CERN Document Server

    Auciello, Orlando

    1989-01-01

    Plasma Diagnostics, Volume 1: Discharge Parameters and Chemistry covers seven chapters on the important diagnostic techniques for plasmas and details their use in particular applications. The book discusses optical diagnostic techniques for low pressure plasmas and plasma processing; plasma diagnostics for electrical discharge light sources; as well as Langmuir probes. The text also describes the mass spectroscopy of plasmas, microwave diagnostics, paramagnetic resonance diagnostics, and diagnostics in thermal plasma processing. Electrical engineers, nuclear engineers, microwave engineers, che

  14. Development of a simple chromatographic method for the determination of piracetam in human plasma and its pharmacokinetic evaluation.

    Science.gov (United States)

    Barkat, K; Ahmad, M; Minhas, M U; Malik, M Z; Sohail, M

    2014-07-01

    The objective of study was to develop an accurate and reproducible HPLC method for determination of piracetam in human plasma and to evaluate pharmacokinetic parameters of 800 mg piracetam. A simple, rapid, accurate, precise and sensitive high pressure liquid chromatography method has been developed and subsequently validated for determination of piracetam. This study represents the results of a randomized, single-dose and single-period in 18 healthy male volunteers to assess pharmacokinetic parameters of 800 mg piracetam tablets. Various pharmacokinetic parameters were determined from plasma for piracetam and found to be in good agreement with previous reported values. The data was analyzed by using Kinetica® version 4.4 according to non-compartment model of pharmacokinetic analysis and after comparison with previous studies, no significant differences were found in present study of tested product. The major pharmacokinetic parameters for piracetam were as follows: t1/2 was (4.40 ± 0.179) h; Tmax value was (2.33 ± 0.105) h; Cmax was (14.53 ± 0.282) µg/mL; the AUC(0-∞) was (59.19 ± 4.402) µg · h/mL. AUMC(0-∞) was (367.23 ± 38.96) µg. (h)(2)/mL; Ke was (0.16 ± 0.006) h; MRT was (5.80 ± 0.227) h; Vd was (96.36 ± 8.917 L). A rapid, accurate and precise high pressure liquid chromatography method was developed and validated before the study. It is concluded that this method is very useful for the analysis of pharmacokinetic parameters, in human plasma and assured the safety and efficacy of piracetam, can be effectively used in medical practice. © Georg Thieme Verlag KG Stuttgart · New York.

  15. Evaluation of methods for estimating population pharmacokinetics parameters. I. Michaelis-Menten model: routine clinical pharmacokinetic data.

    Science.gov (United States)

    Sheiner, L B; Beal, S L

    1980-12-01

    Individual pharmacokinetic par parameters quantify the pharmacokinetics of an individual, while population pharmacokinetic parameters quantify population mean kinetics, interindividual variability, and residual intraindividual variability plus measurement error. Individual pharmacokinetics are estimated by fitting individual data to a pharmacokinetic model. Population pharmacokinetic parameters are estimated either by fitting all individual's data together as though there was no individual kinetic differences (the naive pooled data approach), or by fitting each individual's data separately, and then combining the individual parameter estimates (the two-stage approach). A third approach, NONMEM, takes a middle course between these, and avoids shortcomings of each of them. A data set consisting of 124 steady-state phenytoin concentration-dosage pairs from 49 patients, obtained in the routine course of their therapy, was analyzed by each method. The resulting population parameter estimates differ considerably (population mean Km, for example, is estimated as 1.57, 5.36, and 4.44 micrograms/ml by the naive pooled data, two-stage, and NONMEN approaches, respectively). Simulations of the data were analyzed to investigate these differences. The simulations indicate that the pooled data approach fails to estimate variabilities and produces imprecise estimates of mean kinetics. The two-stage approach produces good estimates of mean kinetics, but biased and imprecise estimates of interindividual variability. NONMEN produces accurate and precise estimates of all parameters, and also reasonable confidence intervals for them. This performance is exactly what is expected from theoretical considerations and provides empirical support for the use of NONMEM when estimating population pharmacokinetics from routine type patient data.

  16. A physiologically based pharmacokinetic model to predict the pharmacokinetics of highly protein-bound drugs and the impact of errors in plasma protein binding.

    Science.gov (United States)

    Ye, Min; Nagar, Swati; Korzekwa, Ken

    2016-04-01

    Predicting the pharmacokinetics of highly protein-bound drugs is difficult. Also, since historical plasma protein binding data were often collected using unbuffered plasma, the resulting inaccurate binding data could contribute to incorrect predictions. This study uses a generic physiologically based pharmacokinetic (PBPK) model to predict human plasma concentration-time profiles for 22 highly protein-bound drugs. Tissue distribution was estimated from in vitro drug lipophilicity data, plasma protein binding and the blood: plasma ratio. Clearance was predicted with a well-stirred liver model. Underestimated hepatic clearance for acidic and neutral compounds was corrected by an empirical scaling factor. Predicted values (pharmacokinetic parameters, plasma concentration-time profile) were compared with observed data to evaluate the model accuracy. Of the 22 drugs, less than a 2-fold error was obtained for the terminal elimination half-life (t1/2 , 100% of drugs), peak plasma concentration (Cmax , 100%), area under the plasma concentration-time curve (AUC0-t , 95.4%), clearance (CLh , 95.4%), mean residence time (MRT, 95.4%) and steady state volume (Vss , 90.9%). The impact of fup errors on CLh and Vss prediction was evaluated. Errors in fup resulted in proportional errors in clearance prediction for low-clearance compounds, and in Vss prediction for high-volume neutral drugs. For high-volume basic drugs, errors in fup did not propagate to errors in Vss prediction. This is due to the cancellation of errors in the calculations for tissue partitioning of basic drugs. Overall, plasma profiles were well simulated with the present PBPK model. Copyright © 2016 John Wiley & Sons, Ltd.

  17. An Evaluation of Using Population Pharmacokinetic Models to Estimate Pharmacodynamic Parameters for Propofol and Bispectral Index in Children

    NARCIS (Netherlands)

    Coppens, Marc J.; Eleveld, Douglas J.; Proost, Johannes H.; Marks, Luc A. M.; Van Bocxlaer, Jan F. P.; Vereecke, Hugo; Absalom, Anthony R.; Struys, Michel M. R. F.

    Background: To study propofol pharmacodynamics in a clinical setting a pharmacokinetic model must be used to predict drug plasma concentrations. Some investigators use a population pharmacokinetic model from existing literature and minimize the pharmacodynamic objective function. The purpose of the

  18. Pharmacokinetic Modeling of Intranasal Scopolamine in Plasma Saliva and Urine

    Science.gov (United States)

    Wu, L.; Tam, V. H.; Chow, D. S. L.; Putcha, L.

    2015-01-01

    An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS). The bioavailability and pharmacokinetics (PK) were evaluated under IND (Investigational New Drug) guidelines. The aim of the project was to develop a PK model that can predict the relationships among plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trial protocol with INSCOP. Twelve healthy human subjects were administered at three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min to 24 h after dosing and scopolamine concentrations were measured by using a validated LC-MS-MS assay. PK compartmental models, using actual dosing and sampling time, were established using Phoenix (version 1.2). Model selection was based on a likelihood ratio test on the difference of criteria (-2LL (i.e. log-likelihood ratio test)) and comparison of the quality of fit plots. The results: Predictable correlations among scopolamine concentrations in compartments of plasma, saliva and urine were established, and for the first time the model satisfactorily predicted the population and individual PK of INSCOP in plasma, saliva and urine. The model can be utilized to predict the INSCOP plasma concentration by saliva and urine data, and it will be useful for monitoring the PK of scopolamine in space and other remote environments using non-invasive sampling of saliva and/or urine.

  19. Quantification of etodolac in human plasma for pharmacokinetics and bioequivalence studies in 27 Korean subjects.

    Science.gov (United States)

    Song, Il-Dong; Kang, Je-Seop; Kim, Hyun-Jin; Kim, Se-Mi; Zhao, Dong-Xu; Kim, Shin-Hee; Chun, Min-Young; Lee, Kyuhyun

    2017-01-16

    We developed a simple and validated liquid chromatography tandem mass spectrometry(LC-MS/MS) for quantification of etodolac using pioglitazone as an internal standard (IS) to assess pharmacokinetics and to appraise bioequivalence of two formulations of etodolac (reference and tested) in 27 healthy Korean subjects. Isocratic mobile phase consisted of 10 mM ammonium formate and acetonitrile were used to separate the analytes on a Gemini C18 column. Also, analytes were analyzed by MS/MS in multiple reaction monitoring (MRM) mode using the transitions of (M+H)+ ions, m/z 288.2→172.3 and m/z 357.1→134.2 for quantification of etodolac and IS each. The standard calibration curves displayed significant linearity within the range of 0.2-30.0 μg/mL (r2=0.9956, 1/x2 weighting) with LLOQ of 0.1 μg/mL. The retention times of etodolac and the IS were 0.77 min and 0.57 min each, indicating the high-throughput potential of the proposed method. The pharmacokinetic parameters were calculated from the plasma samples and data form the reference and test drugs were represented as follows; Area under plasma concentration-time curve (AUCt) (78.03 vs. 84.00 μg×h/mL), AUC∞ (86.67 vs. 93.92 μg×h/mL), maximal plasma concentration (Cmax) (19.49 vs. 18.94 μg/mL), time for maximal concentrations (Tmax) (2.13 vs. 2.26 h), Plasma elimination half-life (T1/2) (8.12 vs. 8.47 h), elimination rate constant (λz) (0.0853 vs. 0.0818 h-1). Pharmacokinetic parameters with 90% confidence interval fall within the bioequivalence range of 80-125%. Thus, the new testified method was successfully applied for the pharmacokinetic and bioequivalence studies for two etodolac formulations.

  20. Plasma paracetamol concentrations and pharmacokinetics following rectal administration in neonates and young infants

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing; O'Brien, K; Morton, N S

    1999-01-01

    Despite widespread use in children pharmacokinetic data about paracetamol are relatively scarce, not the least in the youngest age groups. This study aimed to describe plasma paracetamol concentrations and pharmacokinetics of a single rectal paracetamol dose in neonates and young infants....

  1. Plasma paracetamol concentrations and pharmacokinetics following rectal administration in neonates and young infants

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing; O'Brien, K; Morton, N S

    1999-01-01

    Despite widespread use in children pharmacokinetic data about paracetamol are relatively scarce, not the least in the youngest age groups. This study aimed to describe plasma paracetamol concentrations and pharmacokinetics of a single rectal paracetamol dose in neonates and young infants....

  2. Metabolic and pharmacokinetic studies of scutellarin in rat plasma, urine, and feces

    Institute of Scientific and Technical Information of China (English)

    Jian-feng XING; Hai-sheng YOU; Ya-lin DONG; Jun LU; Si-ying CHEN; Hui-fang ZHU; Qian DONG; Mao-yi WANG; Wei-hua DONG

    2011-01-01

    Aim: To study the metabolic and pharmacokinetic profile of scutellarin, an active component from the medical plant Erigeron brevis-capus (Vant) Hand-Mazz, and to investigate the mechanisms underlying the low bioavailability of scutellarin though oral or intravenous administration in rats.Methods: HPLC method was developed for simultaneous detection of scutellarin and scutellarein (the aglycone of scutellarin) in rat plasma, urine and feces. The in vitro metabolic stability study was carried out in rat liver microsomes from different genders. Results. After a single oral dose of scutellarin (400 mg/kg), the plasma concentrations of scutellarin and scutellarein in female rats were significantly higher than in male ones. Between the female and male rats, significant differences in AUC, t and C for scutel-larin were found. The pharmacokinetic parameters of scutellarin in the urine also showed significant gender differences. After a single oral dose of scutellarin (400 mg/kg), the total percentage excretion of scutellarein in male and female rats was 16.5% and 8.61%, respectively. The total percentage excretion of scutellarin and scutellarein in the feces was higher with oral administration than with intravenous administration. The in vitro t and CL value for scuteliarin in male rats was significantly higher than that in female rats.Conclusion: The results suggest that a large amount of ingested scutellarin was metabolized into scutellarein in the gastrointestinal tract and then excreted with the feces, leading to the extremely low oral bioavailability of scutellarin. The gender differences of pharma-cokinetic parameters of scutellarin and scutallarein are due to the higher CL and lower absorption in male rats.

  3. The pharmacokinetic characters of simvastatin after co-administration with Shexiang Baoxin Pill in healthy volunteers' plasma.

    Science.gov (United States)

    Tao, Jianfei; Jiang, Peng; Peng, Chengcheng; Li, Min; Liu, Runhui; Zhang, Weidong

    2016-07-15

    To investigate the effect of Shexiang Baoxin Pill (SBP), a tranditional Chinese medicine, on the pharmacokinetic (PK) parameters of simvastatin in healthy volunteers' plasma, a quantitative method was developed using an Agilent G6410A rapid performance liquid chromatography (RPLC) coupled with triple quadrupole mass spectrometry system. The established method was rapid with high extraction recovery and successfully applied for the determination of simvastatin in plasma of 16 healthy volunteers. The results demonstrated that the MRT(0-∞), T1/2 and Tmax value of simvastatin were significantly decreased, while the AUC(0-t) and Cmax values of smivastatin were increased by SBP. The pharmacokinetic study demonstrated that the metabolism parameters of simvastatin could be affected by SBP and the potential drug-drug interaction should be noted in the future clinical practice.

  4. Integrating Dynamic Positron Emission Tomography and Conventional Pharmacokinetic Studies to Delineate Plasma and Tumor Pharmacokinetics of FAU, a Prodrug Bioactivated by Thymidylate Synthase.

    Science.gov (United States)

    Li, Jing; Kim, Seongho; Shields, Anthony F; Douglas, Kirk A; McHugh, Christopher I; Lawhorn-Crews, Jawana M; Wu, Jianmei; Mangner, Thomas J; LoRusso, Patricia M

    2016-11-01

    FAU, a pyrimidine nucleotide analogue, is a prodrug bioactivated by intracellular thymidylate synthase to form FMAU, which is incorporated into DNA, causing cell death. This study presents a model-based approach to integrating dynamic positron emission tomography (PET) and conventional plasma pharmacokinetic studies to characterize the plasma and tissue pharmacokinetics of FAU and FMAU. Twelve cancer patients were enrolled into a phase 1 study, where conventional plasma pharmacokinetic evaluation of therapeutic FAU (50-1600 mg/m(2) ) and dynamic PET assessment of (18) F-FAU were performed. A parent-metabolite population pharmacokinetic model was developed to simultaneously fit PET-derived tissue data and conventional plasma pharmacokinetic data. The developed model enabled separation of PET-derived total tissue concentrations into the parent drug and metabolite components. The model provides quantitative, mechanistic insights into the bioactivation of FAU and retention of FMAU in normal and tumor tissues and has potential utility to predict tumor responsiveness to FAU treatment.

  5. Sensor for monitoring plasma parameters

    CERN Document Server

    Bolshakov, A A; Sharma, S P; Bol'shakov, Alexander A.; Cruden, Brett A.; Sharma, Surendra P.

    2004-01-01

    A spectrally tunable VCSEL (vertical cavity surface-emitting laser) was used as part of sensing hardware for measurements of the radial-integrated gas temperature inside an inductively coupled plasma reactor. The data were obtained by profiling the Doppler-broadened absorption of metastable Ar atoms at 763.51 nm in argon and argon/nitrogen plasmas (3, 45, and 90% N2 in Ar) at pressure 0.5-70 Pa and inductive power of 100 and 300 W. The results were compared to rotational temperature derived from the N2 emission at the (0,0) transition of the C - B system. The differences in integrated rotational and Doppler temperatures were attributed to non-uniform spatial distributions of both temperature and thermometric species (Ar* and N2*) that varied depending on conditions. A two-dimensional, two-temperature fluid plasma simulation was employed to explain these differences. This work should facilitate further development of a miniature sensor for non-intrusive acquisition of data (temperature and densities of multipl...

  6. [Study on determination of caffeic acid, chlorogenic acid in rat plasma and their pharmacokinetics with LC-MS/MS].

    Science.gov (United States)

    Dai, Guo-Liang; Ma, Shi-Tang; Liu, Shi-Jia; Cheng, Xiao-Gui; Zang, Yu-Xin; Ju, Wen-Zheng; Tan, Heng-Shan

    2013-11-01

    To establish a LC-MS/MS method to determine caffeic acid, chlorogenic acid in rat plasma and study their pharmacokinetics in rats. Six Sprague-Dawley rats were intravenously injected with 4 mL x kg(-1) of Dengzhanxixin injection, respectively. Their drug plasma concentration was determined by LC-MS/MS, with tinidazole as an internal standard. The pharmacokinetic parameters were calculated by DAS 1.0. The linear concentration ranges of caffeic acid, and chlorogenic acid were 2-128 microg x L(-1) (r = 0.998 1) and 3-384 microg x L(-1) (r = 0.998 7), respectively. The methodological test showed conformance to the requirements. The intraday and inter-day variable coefficients were both less than 10.0%, indicating that both of legitimate precise and accuracy were in conformity with the requirements of biological sample analysis. For caffeic acid, the pharmacokinetic parameter t1/2beta AUC0-t, and CL were (130.91 +/- 38.77) min, (4.89 +/- 0.96) mg x min x L(-1) and (0.12 +/- 0.02) L x min(-1) x kg(-1), respectively. For chlorogenic acid, the pharmacokinetic parameter t1/2beta , AUC0-t, and CL were (49.38 +/- 8.85) min, (9.54 +/- 0.95) mg x min x L(-1) and (0.09 +/- 0.003) L x min(-1) x kg(-1), respectively. The LC-MS/MS analysis method established in this study was proved to be so accurate and sensitive that it can be applied to the pharmacokinetic study of caffeic acid and chlorogenic acid.

  7. [Plasma ibuprofen enantiomers and their pharmacokinetics in Beagle dogs determined by HPLC].

    Science.gov (United States)

    Wang, Hong-yan; Kong, Ai-ying; Yang, Bo; Yan, Liang-ping; Di, Xin

    2015-12-01

    A chiral high-performance liquid chromatography method was developed for the simultaneous determination of ibuprofen enantiomers in dog plasma. It was used to study the pharmacokinetics in the Beagle dog after intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen. Ketoprofen was chosen as the internal standard. After a simple precipitation using methanol as the precipitating solvent, both analytes and IS were separated on a Kromasil 100-5CHI-TBB chiral column (250 mm x4.6 mm, 5 μm) with isocratic elution using acetonitrile - 20 mmol x L(-1) phosphate buffer (pH 3.0, containing 5% methanol) (6 : 4) as the mobile phase. The detection wavelength was 220 nm. Liner calibration curves for both of the ibuprofen enantiomers were over the concentration range from 0.5 to 50 μg x mL(-1) with a lower limit of quantification of 0.5 μg x mL(-1), the accuracies were all in standard ranges. The intra- and inter- assay precisions were all below 7%. The recovery rate was 93.1% to 100.4%. The experiments proved that the method was simple, rapid and sensitive. It can be used in the quantitative determination of ibuprofen enantiomers in dog plasma. The method was used to determine the concentration of ibuprofen enantiomers in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen (9 mg x kg(-1)) and the pharmacokinetics parameters were calculated based on the concentration-time curves. The C(max) of S-ibuprofen in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen were 30.8 ± 4.7, 46.1 ± 5.9 and 20.0 ± 2.6 μg x mL(-1), respectively. In terms of the exposure of active ingredient, it revealed a significant difference between the administration of S-ibuprofen and the other two groups. The systematical R- to S- chiral inversion was discussed. Comparing the pharmacokinetic parameters at different doses, chiral inversion were 70.1% ± 36.6% and 76

  8. Pharmacokinetics of methimazole in children and adolescents with Graves' disease. Studies on plasma and intrathyroidal concentrations.

    Science.gov (United States)

    Okuno, A; Yano, K; Inyaku, F; Suzuki, Y; Sanae, N; Kumai, M; Naitoh, Y

    1987-05-01

    Methimazole concentrations in plasma and in the thyroid glands were measured by means of high-performance liquid chromatography. Pharmacokinetics of methimazole were studied after a single oral dose (175 mumol/m2) in nine children and adolescent who were in the thyrotoxic state. Plasma levels of methimazole showed peak concentrations of 4.4 to 12.6 (median 9.2) mumol/l at 0.5 to 4 h after drug administration. Plasma half-life, area under the curve, and distribution volume ranged from 2.73 to 6.04 h, 32.8 to 77.9 mumol X l-1 X h-1, and 0.516 to 0.913 l/kg, respectively. These pharmacokinetic parameters showed a wide variation among the patients, but were quite reproducible in the same subject. Intrathyroidal concentrations of methimazole were measured in another nine subjects including four adolescents and five adults who underwent thyroidectomy. The drug concentrations in the thyroid glands ranged between 3.5 and 23.8 mumol/kg tissue and were far higher than those in the plasma obtained at the time of surgery. In this series of experiments, the dose of the drug varied from 76 to 319 mumol/m2, time after the last dose to surgery from 5 to 24 h, and the mode of drug administration from a single to three divided doses. Among these variable factors, only the daily dose of methimazole corrected by body surface area showed significant correlation with the intrathyroidal concentration, whereas the time after the last dose of the drug and the mode of drug administration did not.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. The pharmacokinetic study of rutin in rat plasma based on an electrochemically reduced graphene oxide modified sensor$

    Institute of Scientific and Technical Information of China (English)

    Pei Zhang a; Yu-Qiang Gou b; Xia Gao a; Rui-Bin Bai a; Wen-Xia Chen a; Bo-Lu Sun a; Fang-Di Hu a; n; Wang-Hong Zhao c

    2016-01-01

    An electrochemical method based on a directly electrochemically reduced graphene oxide (ERGO) film coated on a glassy carbon electrode (GCE) was developed for the rapid and convenient determination of rutin in plasma. ERGO was modified on the surface of GCE by one-step electro-deposition method. Electrochemical behavior of rutin on ERGO/GCE indicated that rutin underwent a surface-controlled quasi-reversible process and the electrochemical parameters such as charge transfer coefficient (α), electron transfer number (n) and electrode reaction standard rate constant (ks) were 0.53, 2 and 3.4 s?1, respectively. The electrochemical sensor for rutin in plasma provided a wide linear response range of 4.70 ? 10 ? 7 ? 1.25 ? 10 ? 5 M with the detection limit (s/n ¼ 3) of 1.84 ? 10 ? 8 M. The assay was success-fully used to the pharmacokinetic study of rutin. The pharmacokinetic parameters such as elimination rate half-life (t1/2), area under curve (AUC), and plasma clearance (CL) were calculated to be 3.345 7 0.647 min, 5750 7 656.0 mg min/mL, and 5.891 7 0.458 mL/min/kg, respectively. The proposed method utilized a small sample volume of 10μL and had no complicated sample pretreatment (without deproteinization), which was simple, eco-friendly, and time-and cost-efficient for rutin pharmacokinetic studies.

  10. Estimation of pharmacokinetic parameters from non-compartmental variables using Microsoft Excel.

    Science.gov (United States)

    Dansirikul, Chantaratsamon; Choi, Malcolm; Duffull, Stephen B

    2005-06-01

    This study was conducted to develop a method, termed 'back analysis (BA)', for converting non-compartmental variables to compartment model dependent pharmacokinetic parameters for both one- and two-compartment models. A Microsoft Excel spreadsheet was implemented with the use of Solver and visual basic functions. The performance of the BA method in estimating pharmacokinetic parameter values was evaluated by comparing the parameter values obtained to a standard modelling software program, NONMEM, using simulated data. The results show that the BA method was reasonably precise and provided low bias in estimating fixed and random effect parameters for both one- and two-compartment models. The pharmacokinetic parameters estimated from the BA method were similar to those of NONMEM estimation.

  11. Simultaneous Determination of Silybin A and Silybin B in Rat Plasma and Pharmacokinetic Study

    Institute of Scientific and Technical Information of China (English)

    CHU Yang; LI Wei; LI Zhi-wen; LI Xin-xin; MA Xiao-hui; ZHOU Shui-ping; ZHU Yong-hong

    2011-01-01

    Objective To investigate the bioavailability and pharmacokinetics of silybin A and silybin B in rats,respectively.Methods Following iv and ig administration of silybin to 20 Wistar rats,the plasma samples were collected at different time points up to 12 h.Sample pretreatment was involved in one-step protein precipitation with acetonitrile.Silybin A and silybin B were simultaneously determined by LC-MS/MS.Results After ig dosing silybin 28,56,and 112 mg/kg to rats,the t1/2β values were 5.48,5.08,and 5.73 h for silybin A,and 4.56,4.12,and 5.53 h for silybin B; The Cmax were 674.3,1349.4,and 2042.5 ng/mL for silybin A,and 671.0,1365.4,and 2066.2 ng/mL for silybin B; The Tmax were 0.20,0.23,and 0.20 h for silybin A,and 0.20,0.23,and 0.20 h for silybin B; The AUC were 454.4,845.9,and 1219.5 h·ng/mL for silybin A,and 432.0,817.1,and 1153.6 h·ng/mL for silybin B.The absolute bioavailabilities of silybin A and silybin B were 2.86% and 1.93%,respectively.Conclusion Silybin A and silybin B have very low bioavailability after ig administration,and there is no significant difference in the pharmacokinetic parameters between silybin A and silybin B,which indicates that the two diastereoisomers have similar pharmacokinetic behavior in rats.

  12. Parameter Estimation of Population Pharmacokinetic Models with Stochastic Differential Equations: Implementation of an Estimation Algorithm

    Directory of Open Access Journals (Sweden)

    Fang-Rong Yan

    2014-01-01

    Full Text Available Population pharmacokinetic (PPK models play a pivotal role in quantitative pharmacology study, which are classically analyzed by nonlinear mixed-effects models based on ordinary differential equations. This paper describes the implementation of SDEs in population pharmacokinetic models, where parameters are estimated by a novel approximation of likelihood function. This approximation is constructed by combining the MCMC method used in nonlinear mixed-effects modeling with the extended Kalman filter used in SDE models. The analysis and simulation results show that the performance of the approximation of likelihood function for mixed-effects SDEs model and analysis of population pharmacokinetic data is reliable. The results suggest that the proposed method is feasible for the analysis of population pharmacokinetic data.

  13. Early Therapeutic Intervention for Crush Syndrome: Characterization of Intramuscular Administration of Dexamethasone by Pharmacokinetic and Biochemical Parameters in Rats

    National Research Council Canada - National Science Library

    Murata, Isamu; Goto, Mai; Komiya, Masahiro; Motohashi, Risa; Hirata, Momoko; Inoue, Yutaka; Kanamoto, Ikuo

    2016-01-01

    .... We demonstrated the utility of intramuscular administration of dexamethasone (DEX) in disaster medical care by using a model of CS to characterize the pharmacokinetics and biochemical parameters...

  14. Optimization of audio - ultrasonic plasma system parameters

    Science.gov (United States)

    Haleem, N. A.; Abdelrahman, M. M.; Ragheb, M. S.

    2016-10-01

    The present plasma is a special glow plasma type generated by an audio ultrasonic discharge voltage. A definite discharge frequency using a gas at a narrow band pressure creates and stabilizes this plasma type. The plasma cell is a self-extracted ion beam; it is featured with its high output intensity and its small size. The influence of the plasma column length on the output beam due to the variation of both the audio discharge frequency and the power applied to the plasma electrodes is investigated. In consequence, the aim of the present work is to put in evidence the parameters that influence the self-extracted collected ion beam and to optimize the conditions that enhance the collected ion beam. The experimental parameters studied are the nitrogen gas, the applied frequency from 10 to 100 kHz, the plasma length that varies from 8 to 14 cm, at a gas pressure of ≈ 0.25 Torr and finally the discharge power from 50 to 500 Watt. A sheet of polyethylene of 5 micrometer covers the collector electrode in order to confirm how much ions from the beam can go through the polymer and reach the collector. To diagnose the occurring events of the beam on the collector, the polymer used is analyzed by means of the FTIR and the XRF techniques. Optimization of the plasma cell parameters succeeded to enhance and to identify the parameters that influence the output ion beam and proved that its particles attaining the collector are multi-energetic.

  15. Quantitation of eleven active compounds of Aidi injection in rat plasma and its application to comparative pharmacokinetic study.

    Science.gov (United States)

    Liu, Ran; Ma, Ran; Yu, Chunyu; Bi, Cathy Wenchuan; Yin, Yidi; Xu, Huarong; Shang, Hongwei; Bi, Kaishun; Li, Qing

    2016-07-15

    Aidi injection has been widely used for the treatment of colorectal cancer. The purpose of this study was to develop a sensitive and reliable method for simultaneous quantitation of 11 main active ingredients in Aidi injection and to compare the pharmacokinetics of these ingredients in normal and colorectal model cancer rats after tail vein injection. After being extracted by isopropanol-ethyl acetate (1:1, v/v), the plasma samples were analyzed with domperidone as internal standard. Then the analytes were separated on a Venusil MP C18 column with 0.15% formic acid and methanol. The detection was performed on HPLC-MS/MS system with turbo ion spray source in the positive ion and multiple reaction-monitoring mode. The assay was shown to be linear over the range of 0.004-4.0μgmL(-1) of syringin B, astragaloside II and isofraxidin; 0.01-10.0μgmL(-1) of calycosin-7-O-β-d-glucoside and astragaloside IV; 0.02-20.0μgmL(-1) of ginsenoside Rg1, Rb1, Rc and Rd; 0.04-40.0μgmL(-1) of syringin E; 0.06-60.0μgmL(-1) of ginsenoside Re. And the validated method has been successfully applied to compare pharmacokinetic profiles of the 11 ingredients in plasma. The pharmacokinetic results showed here were significant differences in pharmacokinetic parameters for eight analytes between two groups after injection, while no significant differences for astragaloside II, astragaloside IV and ginsenoside Rc. The present study has the advantages of short analysis time and easy sample preparation, which could more comprehensively reflect the quality of Aidi injection in single run. The method proposed could be of great use for pharmacokinetics, bioavailability or bioequivalence studies of Aidi injection in biological samples.

  16. Validation of a HPLC-tandem MS/MS method for pharmacokinetics study of (+)-pinoresinol-di-β-D-glucopyranoside from Eucommia ulmoides Oliv extract in rats' plasma.

    Science.gov (United States)

    Wang, Jia-Long; Liu, Er-Wei; Zhang, Yi; Wang, Tao; Han, Li-feng; Gao, Xiu-Mei

    2012-01-31

    Natural plant compounds have an unexceptional influence in pharmacy as they provide an uncountable number of invaluable lead molecules. Phytochemical researches nowadays focus on bio-assay guided revealing of the therapeutic profile and synergism of medicinal herbs and their constituents. Assessing the clinical and biological potential and determining the pharmacokinetics of herbal constituents is also an area of much interest. This work was conducted in order to carry out a sensitive liquid chromatography tandem mass spectrum (HPLC-MS/MS) method for the pharmacokinetics study of (+)-pinoresinol-di-β-D-glucopyranoside (PG) in rats' plasma after oral administration of Eucommia ulmoides Oliv extract. The validated method was by means of linearity, precision, matrix effect and recovery so that it could be used for the pharmacokinetic study of PG. The obtained pharmacokinetic parameters shown that PG pertains to one-compartment model and 95% of PG was eliminated within 12h.

  17. Effect of piperine on pharmacokinetics of sodium valproate in plasma samples of rats using gas chromatography-mass spectrometry method

    Directory of Open Access Journals (Sweden)

    Bushra Parveen

    2015-01-01

    Full Text Available Piperine (PIP is used as anticonvulsant in traditional Chinese medicine. Co-administration of low-dose sodium valproate with PIP has been regarded to have potential anticonvulsant activity. Aim: This study was intended to investigate the effect of PIP on the pharmacokinetics of sodium valproate (SVP in the plasma samples of rats using gas chromatography-mass spectrometry (GC-MS method. Materials and Methods: The plasma samples obtained after oral administration of SVP, 150 mg/kg and SVP, 150 mg/kg + PIP, and 5 mg/kg to male Wistar rats were used to quantify the concentrations in plasma using GC-MS method. Results: A simple and accurate method developed in-house was applied for the analysis of plasma samples of Wistar rats after oral administration of SVP and PIP + sodium valproate, respectively. The pharmacokinetic parameters reported 14.8-fold increase in plasma concentration (maximum observed concentration in the concentration-time profile, 4.6-fold increase in area under the curve and slightly prolonged time to reach that concentration (1 h of SVP in presence of PIP. Conclusion: The study reaffirms the bioenhancing effect of PIP suggesting possibility of dose reduction of SVP while co-adminstering with PIP.

  18. Nanoparticle Drug Loading as a Design Parameter to Improve Docetaxel Pharmacokinetics and Efficacy

    Science.gov (United States)

    Chu, Kevin S.; Schorzman, Allison N.; Finniss, Mathew C.; Bowerman, Charles J.; Peng, Lei; Luft, J. Christopher; Madden, Andrew; Wang, Andrew Z.; Zamboni, William C.; DeSimone, Joseph M.

    2013-01-01

    Nanoparticle (NP) drug loading is one of the key defining characteristics of a NP formulation. However, the effect of NP drug loading on therapeutic efficacy and pharmacokinetics has not been thoroughly evaluated. Herein, we characterized the efficacy, toxicity and pharmacokinetic properties of NP docetaxel formulations that have differential drug loading but are otherwise identical. Particle Replication in Non-wetting Templates (PRINT®), a soft-lithography fabrication technique, was used to formulate NPs with identical size, shape and surface chemistry, but with variable docetaxel loading. The lower weight loading (9%-NP) of docetaxel was found to have a superior pharmacokinetic profile and enhanced efficacy in a murine cancer model when compared to that of a higher docetaxel loading (20%-NP). The 9%-NP docetaxel increased plasma and tumor docetaxel exposure and reduced liver, spleen and lung exposure when compared to that of 20%-NP docetaxel. PMID:23899444

  19. Sensitivity of transient synchrotron radiation to tokamak plasma parameters

    Energy Technology Data Exchange (ETDEWEB)

    Fisch, N.J.; Kritz, A.H.

    1988-12-01

    Synchrotron radiation from a hot plasma can inform on certain plasma parameters. The dependence on plasma parameters is particularly sensitive for the transient radiation response to a brief, deliberate, perturbation of hot plasma electrons. We investigate how such a radiation response can be used to diagnose a variety of plasma parameters in a tokamak. 18 refs., 13 figs.

  20. Human plasma concentrations of cytochrome P450 probes extrapolated from pharmacokinetics in cynomolgus monkeys using physiologically based pharmacokinetic modeling.

    Science.gov (United States)

    Shida, Satomi; Utoh, Masahiro; Murayama, Norie; Shimizu, Makiko; Uno, Yasuhiro; Yamazaki, Hiroshi

    2015-01-01

    1. Cynomolgus monkeys are widely used in preclinical studies as non-human primate species. Pharmacokinetics of human cytochrome P450 probes determined in cynomolgus monkeys after single oral or intravenous administrations were extrapolated to give human plasma concentrations. 2. Plasma concentrations of slowly eliminated caffeine and R-/S-warfarin and rapidly eliminated omeprazole and midazolam previously observed in cynomolgus monkeys were scaled to human oral biomonitoring equivalents using known species allometric scaling factors and in vitro metabolic clearance data with a simple physiologically based pharmacokinetic (PBPK) model. Results of the simplified human PBPK models were consistent with reported experimental PK data in humans or with values simulated by a fully constructed population-based simulator (Simcyp). 3. Oral administrations of metoprolol and dextromethorphan (human P450 2D probes) in monkeys reportedly yielded plasma concentrations similar to their quantitative detection limits. Consequently, ratios of in vitro hepatic intrinsic clearances of metoprolol and dextromethorphan determined in monkeys and humans were used with simplified PBPK models to extrapolate intravenous PK in monkeys to oral PK in humans. 4. These results suggest that cynomolgus monkeys, despite their rapid clearance of some human P450 substrates, could be a suitable model for humans, especially when used in conjunction with simple PBPK models.

  1. Comparative pharmacokinetic studies of borneol in mouse plasma and brain by different administrations

    Institute of Scientific and Technical Information of China (English)

    Jing-yi ZHAO; Yang LU; Shou-ying DU; Xiao SONG; Jie BAI; Yue WANG

    2012-01-01

    Borneol,a monoterpenoid alcohol,is used widely,particularly in combined formulas for preventing and curing cardiovascular and cerebrovascular diseases in traditional Chinese medicine.In order to understand the blood and brain pharmacokinetics after intravenous,intranasal,or oral administration and to investigate the superiority and feasibility of intranasal administration,a simple gas chromatographic (GC) method with flame ionization detection (FID) was developed for the quantification of borneol.Blood samples and brain were collected from mice at 1,3,5,10,20,30,60,90,and 120 min after intravenous,intranasal,or oral administration of borneol at a dosage of 30.0 mg/kg.Sample preparations were carried out by liquid-liquid extraction with an internal standard solution of octadecane.The pharmacokinetic parameters were calculated by the software of Kinetica.The calibration curves were linear in the range of 0.11-84.24 μg/ml and 0.16-63.18 μg/g for borneol in plasma and brain,respectively.The methodological and extraction recoveries were both in the range of 85%-115%.The intra-day and inter-day variabilities for plasma and brain samples were ≤5.00% relative standard deviation (RSD).The absolute bioavailabilities F of intranasal and oral administrations were 90.68% and 42.99%.The relative brain targeted coefficients Re of intranasal and oral administrations were 68.37% and 38.40%.The GC-FID method developed could be applied to determination and pharmacokinetic study.The borneol from injection was distributed and metabolized fast without absorption process.The borneol from oral administration was distributed more slowly and had the lowest absolute bioavailability.Nasal administration of borneol was quickly absorbed into the blood and brain,was easy to use and had a greater safety than infection,which makes it worthy of further development as an administration route for encephalopathy treatment.

  2. Pharmacokinetic parameters and biodistribution of soluble cytokine receptors.

    Science.gov (United States)

    Jacobs, C A; Beckmann, M P; Mohler, K; Maliszewski, C R; Fanslow, W C; Lynch, D H

    1993-01-01

    The potential use of soluble cytokine receptors as therapeutics in disease states when excessive or prolonged cytokine expression leads to pathogenesis is just beginning (Van Brunt, 1989). The inhibitory effects of soluble receptors have been found to be highly potent and specific for their respective cytokines (Maliszewski and Fanslow, 1990; Maliszewski et al., 1990). Recent in vivo data have shown that exogenously administered soluble receptors can function as cytokine antagonists and suppress autoimmune inflammatory responses (Jacobs et al., 1991a), allograft rejection, and alloreactivity (Fanslow et al., 1990b). The proposed frequency of administration and dosage of a therapeutic agent is dependent on the half-life of the agent and the route of administration. The elimination or half-life of a drug usually depends on its physiochemical properties (molecular size, glycosylation, isoelectric point, and hydrophobic/hydrophilic properties) (DiPalma and DiGregorio, 1990; Katzung, 1984). The half-life will also depend on the mechanism of clearance for that specific receptor. Once pharmacokinetic data are available for soluble receptors, the therapeutic potential of these molecules can be better evaluated. Only limited pharmacokinetic data are currently available for soluble cytokine receptors (Jacobs et al., 1991b). For sIL-1R, the majority of an intravenously administered dose was cleared in the second elimination phase, with a reasonably long half-life (6.3 hr), such that the entire dose was not eliminated until 35 hr. If administration is by subcutaneous injection, the half-life was even more prolonged. One explanation for the prolonged half-life is the minimal distribution to liver and kidneys and thus low levels of clearance by these organs. In contrast, elimination of intravenously administered sIL-4R was relatively rapid, with a short half-life (2.3 hr). This appeared mainly due to liver distribution and clearance, which has been the highest observed for any

  3. Determination of roxithromycin in human plasma by HPLC with fluorescence and UV absorbance detection: application to a pharmacokinetic study.

    Science.gov (United States)

    Główka, Franciszek K; Karaźniewicz-Łada, Marta

    2007-06-01

    A selective HPLC method with fluorescence detection for the determination of roxithromycin (ROX) in human plasma was described. After solid-phase extraction (SPE), ROX and erythromycin (internal standard, I.S.) were derivatized by treatment with 9-fluorenylmethyl chloroformate (FMOC-Cl). Optimal resolution of fluorescence derivatives of ROX and I.S. was obtained during one analytical run using reversed phase, C(18) column. The mobile phase was composed of potassium dihydrogenphosphate solution, pH 7.5 and acetonitrile. Fluorescence of the compounds was measured at the maximum excitation, 255 nm and emission, 313 nm, of ROX derivatives. Validation parameters of the method were also established. After SPE, differences in recoveries of ROX and erythromycin from human plasma were observed. The linear range of the standard curve of ROX in plasma was 0.5-10.0 mg/l. The validated method was successfully applied for pharmacokinetic studies of ROX after administration of a single tablet of ROX.

  4. Development and Validation of Acyclovir HPLC External Standard Method in Human Plasma: Application to Pharmacokinetic Studies

    Directory of Open Access Journals (Sweden)

    Selvadurai Muralidharan

    2014-01-01

    Full Text Available A simple, rapid, and selective RP-HPLC method was developed for the estimation of acyclovir in human plasma. The method involves a simple protein precipitation technique. Chromatographic separation was carried out on a reverse phase C18 column using mixture of 5 mM ammonium acetate (pH 4.0 and acetonitrile (40 : 60, v/v at a flow rate of 1.0 mL/min with UV detection at 290 nm. The retention time of acyclovir was 4.12 minutes. The method was validated and found to be linear in the range of 25.0–150.0 ng/mL. Validation studies were achieved by using the fundamental parameters, including accuracy, precision, selectivity, sensitivity, linearity and range, stability studies, limit of detection (LOD, and limit of quantitation (LOQ. It shows recovery at 91.0% which is more precise and accurate compared to the other method. These results indicated that the bioanalytical method was linear, precise, and accurate. The new bioanalytical method was successfully applied to a pharmacokinetic linearity study in human plasma.

  5. The pharmacokinetic study of rutin in rat plasma based on an electrochemically reduced graphene oxide modified sensor

    Directory of Open Access Journals (Sweden)

    Pei Zhang

    2016-04-01

    Full Text Available An electrochemical method based on a directly electrochemically reduced graphene oxide (ERGO film coated on a glassy carbon electrode (GCE was developed for the rapid and convenient determination of rutin in plasma. ERGO was modified on the surface of GCE by one-step electro-deposition method. Electrochemical behavior of rutin on ERGO/GCE indicated that rutin underwent a surface-controlled quasi-reversible process and the electrochemical parameters such as charge transfer coefficient (α, electron transfer number (n and electrode reaction standard rate constant (ks were 0.53, 2 and 3.4 s−1, respectively. The electrochemical sensor for rutin in plasma provided a wide linear response range of 4.70×10−7−1.25×10−5 M with the detection limit (s/n=3 of 1.84×10−8 M. The assay was successfully used to the pharmacokinetic study of rutin. The pharmacokinetic parameters such as elimination rate half-life (t1/2, area under curve (AUC, and plasma clearance (CL were calculated to be 3.345±0.647 min, 5750±656.0 µg min/mL, and 5.891±0.458 mL/min/kg, respectively. The proposed method utilized a small sample volume of 10 μL and had no complicated sample pretreatment (without deproteinization, which was simple, eco-friendly, and time- and cost-efficient for rutin pharmacokinetic studies.

  6. Pharmacokinetic study of tramadol and its three metabolites in plasma, saliva and urine

    Directory of Open Access Journals (Sweden)

    M.R Rouini

    2009-12-01

    Full Text Available "nBackground and the purpose of the study: Pharmacokinetic parameters of tramadol and its three metabolites in plasma, saliva and urine following administration of 100 mg single oral dose were investigated in 24 healthy volunteers.Materials and Methods: 12 male and 12 female healthy volunteers received a single oral dose of tramadol and Plasma, mixed saliva -secreted samples without any stimulation and urine were analyzed for Tramadol and its main metabolites by HPLC method.Results and Disscusion: Almost 16.2% of tramadol and 11.2, 1.1 and 5.0% of O-desmethyltramadol (M1, N-desmethyltramadol (M2 and N,O-didesmethyltramadol (M5 respectively were recovered in 30 hrs collected urine. Renal clearance of tramadol, M1, M2 and M5 were 114.7 ± 44.5, 193.9 ± 67.6, 116.1 ± 61.8 and 252.0 ± 91.5 (mL/min respectively. The maximum plasma concentration of tramadol, M1, M2 and M5 were 349.3 ± 76.7, 88.7±30.3, 23.1 ± 11.4 and 30.0 ± 11.7 (ng/mL at 1.6 ± 0.4, 2.4 ± 0.7, 2.8 ± 1.0 and 2.7 ± 1.4 hrs after drug administration respectively. Tramadol and its metabolites appeared in a significant amount in saliva with the saliva/plasma ratios of 9.0, 1.6, 12.3 and 2.8 for tramadol, M1, M2 and M5 according to AUC(0-24 respectively. Conclusion: Conclusion Strong correlations were found between plasma and saliva concentrations for all studied compounds and a dissection to pre and post absorption components improved these correlations. Results o f this study suggests that saliva is a suitable alternative to plasma for clinical and toxicological studies of tramadol and in addition to passive diffusion, a possible active transport is also suggested to describe the elevated saliva/plasma ratios for these compounds.

  7. Application of a novel liquid chromatography/tandem mass spectrometry method for the determination of antazoline in human plasma: Result of ELEPHANT-I [ELEctrophysiological, pharmacokinetic and hemodynamic effects of PHenazolinum (ANTazoline mesylate)] human pharmacokinetic study.

    Science.gov (United States)

    Giebułtowicz, Joanna; Piotrowski, Roman; Baran, Jakub; Kułakowski, Piotr; Wroczyński, Piotr

    2016-05-10

    Antazoline is a first-generation antihistaminic agent with antiarrhythmic quinidine-like properties. In some countries, it is widely used for termination of cardiac arrhythmias, especially atrial fibrillation (AF). However, no human pharmacokinetic studies have been conducted with intravenous antazoline. The aim of our study was to develop and validate a novel liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for the determination of antazoline in human plasma: the ELEPHANT-I [ELEctrophysiological, pharmacokinetic and hemodynamic effects of PHenazolinum (ANTazoline mesylate)] human pharmacokinetic study. Antazoline was extracted from plasma using liquid-liquid extraction. The concentration of the analyte was measured by LC-MS/MS with xylometazoline as an internal standard. The method was validated for linearity, precision, accuracy, stability (freeze/thaw stability, stability in autosampler, short and long term stability), dilution integrity and matrix effect. The analyzed validation criteria were fulfilled. The method was applied to a pharmacokinetic study involving 10 healthy volunteers. Following a single intravenous dose of antazoline mesylate (100 mg), the plasma concentration profile showed a relative fast elimination with a terminal elimination half-life of 2.29 h. A relatively high volume of distribution was observed (Vss=315 L). The values of mean residence time (MRT∞), area under the curve (AUC∞) and clearance were 3.45 h, 0.91 mg h L(-1) and 80.5 L h(-1), respectively. One volunteer showed significant differences in pharmacokinetic parameters. In conclusion, the proposed new LC-MS/MS method was successfully used for the first time for the determination of antazoline in human plasma.

  8. Selected pharmacokinetic parameters for cefovecin in hens and green iguanas

    DEFF Research Database (Denmark)

    Thuesen, Line Risager; Bertelsen, Mads Frost; Brimer, Leon

    2009-01-01

    hens and green iguanas, following subcutaneous injections with 10 mg cefovecin / kg bodyweight. Preliminary studies in eight additional species of birds and reptiles were performed and results were compared with the parameters found in hens and green iguanas. The kinetics were characterized by rapid...

  9. Effect of co-medication on the pharmacokinetic parameters of phenobarbital in asphyxiated newborns.

    Science.gov (United States)

    Šíma, M; Pokorná, P; Hronová, K; Slanař, O

    2015-01-01

    Phenobarbital is an anticonvulsive drug widely used in newborns with hypoxic-ischemic encephalopathy. The objective of our study was to describe possible effect of frequently co-administered medications (dopamine, dobutamine, norepinephrine, furosemide, phenytoin, and analgesics) on the phenobarbital pharmacokinetics in full term newborns with hypoxic-ischemic encephalopathy. Phenobarbital pharmacokinetic parameters (standardized intravenous loading dose was 10-20 mg/kg, maintenance dose 2-6 mg/kg/day) were computed using non-compartmental analysis. Co-medication was evaluated throughout the whole treatment period up to 5 days. Volume of distribution, clearance, and half-life median values (95 % CI) for phenobarbital in the whole study population (n=37) were 0.48 (0.41-0.56) l/kg, 0.0034 (0.0028-0.0040) l/h/kg, and 93.7 (88.1-99.2) h, respectively. Phenobarbital pharmacokinetic parameters were not significantly affected by vasoactive drugs (dopamine, dobutamine, and norepinephrine), furosemide, phenytoin, or analgesics. Furthermore, no dose-dependent alteration of phenobarbital pharmacokinetic parameters was noted for vasoactive medication at doses equivalent to cumulative vasoactive-inotropic score (area under the curve in a plot of vasoactive-inotropic score against time) 143.2-8473.6, furosemide at cumulative doses of 0.2-42.9 mg/kg, or phenytoin at cumulative doses of 10.3-46.2 mg/kg. Phenobarbital pharmacokinetics was not affected by investigated co-administered drugs used in newborns with hypoxic-ischemic encephalopathy in real clinical settings.

  10. Pharmacokinetic study of mangiferin in rat plasma and retina using high-performance liquid chromatography

    Science.gov (United States)

    Hou, Yunlong; Fan, Shengjun; Gu, Yuanqin; Yu, Xuhui; Li, Baoxin

    2010-01-01

    Purpose Although the naturally occurring antioxidant mangiferin has been widely used, it is not yet known whether it can cross the blood-retina barrier (BRB) and enter the eye. The purpose of this experiment was to investigate the ability of mangiferin to pass the blood-retina barrier. Methods Sprague–Dawley rats were used for biologic fluid sampling after intravenous administration of mangiferin at doses of 10, 25, and 50 mg/kg. Blood and retina samples were collected at different time points post-dose. High-performance liquid chromatography (HPLC) separation was conducted on a COSMOSIL 5C18—MS—II column (4.6 mm×250 mm, 5 μm) with a flow rate of 1.0 ml/min using a mobile phase comprised of methanol −2% glacial acetic acid (40:60 v:v). Results The HPLC method has proven suitable to determine the presence of mangiferin in the eye. The plasma concentration of mangiferin was dose dependent. Pharmacokinetic parameters of mangiferin in plasma after intravenous administration were fitted to the two-compartment model with the first-order elimination and first-order transfer between central and peripheral compartments. The concentration of mangiferin in the retina goes with that in the blood. Mangiferin concentrations in the retina reached 5.69±1.48 μg/ml 0.5 h after intravenous administration (50 mg/kg) and then dropped gradually to 0.30±0.02 μg/ml 5.0 h later. The eye–to-plasma concentration ratio was 2.80%. Conclusions Mangiferin can pass the blood-retina barrier after a single intravenous administration and may be a potential natural antioxidant in treating eye diseases. PMID:20806037

  11. A Population Pharmacokinetic Model for Disposition in Plasma, Saliva and Urine of Scopolamine after Intranasal Administration to Healthy Human Subjects

    Science.gov (United States)

    Wu, L.; Tam, V. H.; Chow, D. S. L.; Putcha, L.

    2014-01-01

    An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness. The bioavailability and pharmacokinetics (PK) were evaluated under the Food and Drug Administration guidelines for clinical trials with an Investigative New Drug (IND) protocol. The aim of this project was to develop a PK model that can predict the relationship between plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trials with INSCOP. Methods: Twelve healthy human subjects were administered three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min and 24 h after dosing and scopolamine concentrations were measured by using a validated LC-MS-MS assay. Pharmacokinetic Compartmental models, using actual dosing and sampling times, were built using Phoenix (version 1.2). Model selection was based on the likelihood ratio test on the difference of criteria (-2LL) and comparison of the quality of fit plots. Results: The best structural model for INSCOP (minimal -2LL= 502.8) was established. It consisted of one compartment each for plasma, saliva and urine, respectively, which were connected with linear transport processes except the nonlinear PK process from plasma to saliva compartment. The best-fit estimates of PK parameters from individual PK compartmental analysis and Population PK model analysis were shown in Tables 1 and 2, respectively. Conclusion: A population PK model that could predict population and individual PK of scopolamine in plasma, saliva and urine after dosing was developed and validated. Incorporating a non-linear transfer from plasma to saliva compartments resulted in a significantly improved model fitting. The model could be used to predict scopolamine plasma concentrations from salivary and urinary drug levels, allowing non-invasive therapeutic monitoring of scopolamine in space and other remote environments.

  12. [HPLC-MS/MS method for determination of sodium cromoglycate concentration in human plasma and its pharmacokinetics].

    Science.gov (United States)

    Xu, Xiao-yan; Zhang, Rui; Yuan, Gui-yan; Wang, Ben-jie; Liu, Xiao-yan; Guo, Rui-chen

    2008-09-01

    The study established an HPLC-MS/MS method for determining the concentrations of sodium cromoglycate in human plasma and evaluated the pharmacokinetics of nasal drops and nasal spray. A C18 column was used to separate sodium cromoglycate in plasma with a mobile phase of a mixture of ammonium-methanol (involves 50% acetonitrile) (15:85) at a flow rate of 0.4 mL x min(-1). Electronic spray ionization (ESI) and multiple-reaction monitoring (MRM) were used for the determination of sodium cromoglycate in human plasma. The linear range of the standard curve of sodium cromoglycate was from 0.3 to 20 ng x mL(-1), and the minimum concentration of detection was 0.3 ng x mL(-1). The extraction recovery was more than 94.1%, intra-day and inter-day RSD were less than 14.3%. After a single dose of sodium cromoglycate, the main pharmacokinetic parameters of nasal spray and nasal drops were as follows, T(1/2)(1.82 +/- 0.54) h, (1.59 +/- 0.52) h; Tmax (0.47 +/- 0.12) h, (0.44 +/- 0.15) h; Cmax, (9.79 +/- 4.66) ng x mL(-1), (10.88 +/- 4.05) ng x mL(-1); AUC(0-5 h)(11.52 +/- 3.46) ng x mL(-1) x h x h, (12.63 +/- 4.23) ng x mL(-1) x h, Fr(93.6 +/- 13.8)%. The method is sensitive, rapid and accurate. It is suitable for therapeutic drug monitoring and human pharmacokinetic study of sodium cromoglycate.

  13. Some pharmacokinetic parameters of ampicillin/sulbactam combination after intravenous and intramuscular administration to goats.

    Science.gov (United States)

    Espuny, A; Carceles, C M; Vicente, M S; Escudero, E

    1996-12-01

    Some pharmacokinetic parameters of an ampicillin/sulbactam (2:1) combination were studied in six goats, after intravenous and intramuscular injection at a single dosage of 20 mg/kg bodyweight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam). The drugs were distributed according to an open two-compartment model. The apparent volumes of distribution calculated by the area method of ampicillin and sulbactam were 0.34 +/- 0.04 l/kg and 0.45 +/- 0.15 l/kg, respectively, and the total body clearances were 0.72 +/- 0.11 and 0.38 +/- 0.07 l/kg.h. The half-lives of ampicillin after intravenous and intramuscular administration were 0.32 +/- 0.04 h and 0.71 +/- 0.14 h, respectively. For sulbactam the half-lives were 0.79 +/- 0.18 h and 1.13 +/- 0.21 h after administration by the same routes. The bioavailability after intramuscular injection was high and similar for both drugs (98.29% for ampicillin and 101.84% for sulbactam). The mean peak plasma levels of ampicillin (0.43 +/- 0.27 h) and sulbactam (0.34 +/- 0.14 h) were reached at a similar time, and peak concentrations were also similar and non-proportional to the dose of the products administered (11.02 +/- 3.11 mg/l of ampicillin and 9.5 +/- 0.98 mg/l of sulbactam).

  14. Pharmacokinetic modeling of penciclovir and BRL42359 in the plasma and tears of healthy cats to optimize dosage recommendations for oral administration of famciclovir.

    Science.gov (United States)

    Sebbag, Lionel; Thomasy, Sara M; Woodward, Andrew P; Knych, Heather K; Maggs, David J

    2016-08-01

    OBJECTIVES To determine, following oral administration of famciclovir, pharmacokinetic (PK) parameters for 2 of its metabolites (penciclovir and BRL42359) in plasma and tears of healthy cats so that famciclovir dosage recommendations for the treatment of herpetic disease can be optimized. ANIMALS 7 male domestic shorthair cats. PROCEDURES In a crossover study, each of 3 doses of famciclovir (30, 40, or 90 mg/kg) was administered every 8 or 12 hours for 3 days. Six cats were randomly assigned to each dosage regimen. Plasma and tear samples were obtained at predetermined times after famciclovir administration. Pharmacokinetic parameters were determined for BRL42359 and penciclovir by compartmental and noncompartmental methods. Pharmacokinetic-pharmacodynamic (PK-PD) indices were determined for penciclovir and compared among all dosage regimens. RESULTS Compared with penciclovir concentrations, BRL42359 concentrations were 5- to 11-fold greater in plasma and 4- to 7-fold greater in tears. Pharmacokinetic parameters and PK-PD indices for the 90 mg/kg regimens were superior to those for the 30 and 40 mg/kg regimens, regardless of dosing frequency. Penciclovir concentrations in tears ranged from 18% to 25% of those in plasma. Administration of 30 or 40 mg/kg every 8 hours achieved penciclovir concentrations likely to be therapeutic in plasma but not in tears. Penciclovir concentrations likely to be therapeutic in tears were achieved only with the two 90 mg/kg regimens. CONCLUSIONS AND CLINICAL RELEVANCE In cats, famciclovir absorption is variable and its metabolism saturable. Conversion of BRL42359 to penciclovir is rate limiting. The recommended dosage of famciclovir is 90 mg/kg every 12 hours for cats infected with feline herpesvirus.

  15. Development of a population pharmacokinetic model to describe azithromycin whole-blood and plasma concentrations over time in healthy subjects.

    Science.gov (United States)

    Pene Dumitrescu, T; Anic-Milic, T; Oreskovic, K; Padovan, J; Brouwer, K L R; Zuo, P; Schmith, V D

    2013-07-01

    Azithromycin (AZI), a broad-spectrum antibiotic, accumulates in polymorphonuclear cells and peripheral blood mononuclear cells. The distribution of AZI in proinflammatory cells may be important to the anti-inflammatory properties. Previous studies have described plasma AZI pharmacokinetics. The objective of this study was to describe the pharmacokinetics of AZI in whole blood (concentration in whole blood [Cb]) and plasma (concentration in plasma [Cp]) of healthy subjects. In this study, 12 subjects received AZI (500 mg once a day for 3 days). AZI Cb and Cp were quantified in serial samples collected up to 3 weeks after the last dose and analyzed using noncompartmental and compartmental methods. After the last dose, Cb was greater than Cp. Importantly, Cb, but not Cp, was quantifiable in all but one subject at 3 weeks. The blood area under the curve during a 24-h dosing interval (AUC24) was ∼2-fold greater than the plasma AUC24, but simulations suggested that Cb was not at steady state by day 3. Upon exploration of numerous models, an empirical 3-compartment model adequately described Cp and Cb, but Cp was somewhat underestimated. Intercompartmental clearance (CL; likely representing cells) was lower than apparent oral CL (18 versus 118 liters/h). Plasma, peripheral, and cell compartmental volumes were 439 liters, 2,980 liters, and 3,084 liters, respectively. Interindividual variability in CL was low (26.2%), while the volume of distribution variability was high (107%). This is the first report to describe AZI Cb in healthy subjects, the distribution parameters between Cp and Cb, and AZI retention in blood for up to 3 weeks following 3 daily doses. The model can be used to predict Cb from Cp for AZI under various dosing regimens. (This study has been registered at ClinicalTrials.gov under registration no. NCT01026064.).

  16. Pharmacokinetic Profile of Meropenem, Administered at 500 Milligrams Every 8 Hours, in Plasma and Cantharidin-Induced Skin Blister Fluid

    OpenAIRE

    Maglio, Dana; Teng, Renli; Thyrum, Per T.; Nightingale, Charles H.; Nicolau, David P.

    2003-01-01

    The pharmacokinetic disposition of meropenem, administered at 500 mg every 8 h, in plasma and cantharidin-induced blister fluid is described. Peak meropenem concentrations in blister fluid lagged behind peak meropenem concentrations in plasma, while a lower elimination rate from blister fluid was also noted. The mean penetration of meropenem into blister fluid was 67%. The pharmacokinetic profile of meropenem in blister fluid supports the utility of this dose in the management of skin and sof...

  17. Pharmacokinetic profile of meropenem, administered at 500 milligrams every 8 hours, in plasma and cantharidin-induced skin blister fluid.

    Science.gov (United States)

    Maglio, Dana; Teng, Renli; Thyrum, Per T; Nightingale, Charles H; Nicolau, David P

    2003-05-01

    The pharmacokinetic disposition of meropenem, administered at 500 mg every 8 h, in plasma and cantharidin-induced blister fluid is described. Peak meropenem concentrations in blister fluid lagged behind peak meropenem concentrations in plasma, while a lower elimination rate from blister fluid was also noted. The mean penetration of meropenem into blister fluid was 67%. The pharmacokinetic profile of meropenem in blister fluid supports the utility of this dose in the management of skin and soft tissue infections.

  18. Human plasma concentrations of five cytochrome P450 probes extrapolated from pharmacokinetics in dogs and minipigs using physiologically based pharmacokinetic modeling.

    Science.gov (United States)

    Shida, Satomi; Yamazaki, Hiroshi

    2016-09-01

    The pharmacokinetics of cytochrome P450 probes in humans can be extrapolated from corresponding data in cynomolgus monkeys using simplified physiologically based pharmacokinetic (PBPK) modeling. In the current study, despite some species difference in drug clearances, this modeling methodology was adapted to estimate human plasma concentrations of P450 probes based on data from commonly used medium-sized experimental animals, namely dogs and minipigs. Using known species allometric scaling factors and in vitro metabolic clearance data, the observed plasma concentrations of slowly eliminated caffeine and warfarin and rapidly eliminated omeprazole, metoprolol and midazolam in two young dogs were scaled to human oral monitoring equivalents. Using the same approach, the previously reported pharmacokinetics of the five P450 probes in minipigs was also scaled to human monitoring equivalents. The human plasma concentration profiles of the five P450 probes estimated by the simplified human PBPK models based on observed/reported pharmacokinetics in dogs/minipigs were consistent with previously published pharmacokinetic data in humans. These results suggest that dogs and minipigs, in addition to monkeys, could be suitable models for humans during research into new drugs, especially when used in combination with simple PBPK models.

  19. Rapid and Sensitive Determination of Timosaponin AIII in Rat Plasma by LC-MS/MS and Its Pharmacokinetic Application

    Science.gov (United States)

    Liu, Yanping; Pu, Yiqiong; Zhang, Tong; Ding, Yue; Wang, Bing; Cai, Zhenzhen

    2013-01-01

    A rapid sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for determination of timosaponin AIII (TA-III) in rat plasma, using ginsenoside Re as an internal standard (IS). TA-III and the IS were detected in MRM mode with a negative ionization electrospray mass spectrometer. The calibration curves were linear over the concentration ranges from 11.14 to 1114 ng/mL and the lower limit of quantification (LLOQ) was 11.14 ng/mL. Intra-day and inter-day precisions (RSD) were within 10%, and accuracy ranged from 6.4% to 9.1%. The extraction recovery at three concentrations ranged from 92.3% to 95.5%. The validated method was successfully applied to monitor the concentrations of TA-III in rat plasma after intragastric administration. The best fit pharmacokinetic model to estimate the pharmacokinetic parameters was a single compartment model with weight of 1/x2 for oral administration groups of rats for TA-III. PMID:23434663

  20. Rapid and Sensitive Determination of Timosaponin AIII in Rat Plasma by LC-MS/MS and Its Pharmacokinetic Application

    Directory of Open Access Journals (Sweden)

    Zhenzhen Cai

    2013-02-01

    Full Text Available A rapid sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS method was developed for determination of timosaponin AIII (TA-III in rat plasma, using ginsenoside Re as an internal standard (IS. TA-III and the IS were detected in MRM mode with a negative ionization electrospray mass spectrometer. The calibration curves were linear over the concentration ranges from 11.14 to 1114 ng/mL and the lower limit of quantification (LLOQ was 11.14 ng/mL. Intra-day and inter-day precisions (RSD were within 10%, and accuracy ranged from 6.4% to 9.1%. The extraction recovery at three concentrations ranged from 92.3% to 95.5%. The validated method was successfully applied to monitor the concentrations of TA-III in rat plasma after intragastric administration. The best fit pharmacokinetic model to estimate the pharmacokinetic parameters was a single compartment model with weight of 1/x2 for oral administration groups of rats for TA-III.

  1. Influence of cyclosporine and everolimus on the main mycophenolate mofetil pharmacokinetic parameters

    Science.gov (United States)

    Noreikaitė, Aurelija; Saint-Marcoux, Franck; Marquet, Pierre; Kaduševičius, Edmundas; Stankevičius, Edgaras

    2017-01-01

    Abstract The objective of the present study was to assess the effect of cyclosporine (CsA) on the pharmacokinetic parameters of mycophenolic acid (MPA), an active mycophenolate mofetil (MMF) metabolite, and to compare with the effect of everolimus (EVR). Anonymized medical records of 404 kidney recipients were reviewed. The main MPA pharmacokinetic parameters (AUC(0–12) and Cmax) were evaluated. The patients treated with a higher mean dose of CsA displayed higher MPA AUC(0–12) exposure in the low-dose MMF group (1000 mg/day) (40.50 ± 10.97 vs 28.08 ± 11.03 h mg/L; rs = 0.497, P MMF group (2000 mg/day) (43.00 ± 6.27 vs 28.85 ± 11.08 h mg/L; rs = 0.437, P MMF group (3000 mg/day) (56.75 ± 16.78 vs 36.20 ± 3.70 h mg/L; rs = 0.608, P MMF group (Cmax 22.83 ± 10.82 vs 12.08 ± 5.59 mg/L; rs = 0.507, P MMF group (22.77 ± 8.86 vs 13.00 ± 6.82 mg/L; rs = 0.414, P MMF + CsA and MMF + EVR) showed that MPA AUC(0–12) exposure was by 43% higher in the patients treated with a medium dose of MMF and EVR than in the patients treated with a medium dose of MMF and CsA. The data of the present study suggest a possible CsA versus EVR influence on MMF pharmacokinetics. Study results show that CsA has an impact on the main MPA pharmacokinetic parameters (AUC(0–12) and Cmax) in a CsA dose-related manner, while EVR mildly influence or does not affect MPA pharmacokinetic parameters. Low-dose CsA (lower than 180 mg/day) reduces MPA AUC(0–12) exposure under the therapeutic window and may lead to ineffective therapy, while a high-dose CsA (>240 mg/day) is related to greater than 10 mg/L MPA Cmax and increases the likelihood of adverse events. PMID:28353583

  2. Influence of cyclosporine and everolimus on the main mycophenolate mofetil pharmacokinetic parameters: Cross-sectional study.

    Science.gov (United States)

    Noreikaitė, Aurelija; Saint-Marcoux, Franck; Marquet, Pierre; Kaduševičius, Edmundas; Stankevičius, Edgaras

    2017-03-01

    The objective of the present study was to assess the effect of cyclosporine (CsA) on the pharmacokinetic parameters of mycophenolic acid (MPA), an active mycophenolate mofetil (MMF) metabolite, and to compare with the effect of everolimus (EVR).Anonymized medical records of 404 kidney recipients were reviewed. The main MPA pharmacokinetic parameters (AUC(0-12) and Cmax) were evaluated.The patients treated with a higher mean dose of CsA displayed higher MPA AUC(0-12) exposure in the low-dose MMF group (1000 mg/day) (40.50 ± 10.97 vs 28.08 ± 11.03 h mg/L; rs = 0.497, P MMF group (2000 mg/day) (43.00 ± 6.27 vs 28.85 ± 11.08 h mg/L; rs = 0.437, P MMF group (3000 mg/day) (56.75 ± 16.78 vs 36.20 ± 3.70 h mg/L; rs = 0.608, P MMF group (Cmax 22.83 ± 10.82 vs 12.08 ± 5.59 mg/L; rs = 0.507, P MMF group (22.77 ± 8.86 vs 13.00 ± 6.82 mg/L; rs = 0.414, P MMF + CsA and MMF + EVR) showed that MPA AUC(0-12) exposure was by 43% higher in the patients treated with a medium dose of MMF and EVR than in the patients treated with a medium dose of MMF and CsA.The data of the present study suggest a possible CsA versus EVR influence on MMF pharmacokinetics. Study results show that CsA has an impact on the main MPA pharmacokinetic parameters (AUC(0-12) and Cmax) in a CsA dose-related manner, while EVR mildly influence or does not affect MPA pharmacokinetic parameters. Low-dose CsA (lower than 180 mg/day) reduces MPA AUC(0-12) exposure under the therapeutic window and may lead to ineffective therapy, while a high-dose CsA (>240 mg/day) is related to greater than 10 mg/L MPA Cmax and increases the likelihood of adverse events.

  3. Variation of plasma parameters in a modified mode of plasma production in a double plasma device

    Indian Academy of Sciences (India)

    A Phukan; M K Mishra; B K Saikia; M Chakraborty

    2010-03-01

    A modified mode of plasma production in a double plasma device is presented and plasma parameters are controlled in this configuration. Here plasma is produced by applying a discharge voltage between the hot filaments in the source (cathode) and the target magnetic cage (anode) of the device. In this configuration, the hot electron emitting filaments are present only in the source and the magnetic cage of this is kept at a negative bias such that due to the repulsion of the cage bias, the primary electrons can go to the grounded target and produce plasma there. The plasma parameters can be controlled by varying the voltages applied to the source magnetic cage and the separation grid of the device.

  4. Determination of desmethyldiazepam in plasma by electron-capture GLC: application to pharmacokinetic studies of clorazepate.

    Science.gov (United States)

    Greenblatt, D J

    1978-03-01

    Plasma desmethyldiazepam concentrations were quantitated by a rapid and sensitive technique using electron-capture GLC. Following addition of diazepam as the internal standard, plasma is extracted at physiological pH into benzene-isoamyl alcohol. The extract is evaporated to dryness and reconstituted with toluene-isoamyl alcohol prior to chromatography. Both diazepam and desmethyldiazepam are quantitatively extracted. The variation of identical samples is 5%, and the sensitivity is 5 ng of desmethyldiazepam/ml of original sample. The method is applicable to pharmacokinetic studies of clorazepate, a benzodiazepine derivative transformed to desmethyldiazepam prior to absorption.

  5. Cost-constrained optimal sampling for system identification in pharmacokinetics applications with population priors and nuisance parameters.

    Science.gov (United States)

    Sorzano, Carlos Oscar S; Pérez-De-La-Cruz Moreno, Maria Angeles; Burguet-Castell, Jordi; Montejo, Consuelo; Ros, Antonio Aguilar

    2015-06-01

    Pharmacokinetics (PK) applications can be seen as a special case of nonlinear, causal systems with memory. There are cases in which prior knowledge exists about the distribution of the system parameters in a population. However, for a specific patient in a clinical setting, we need to determine her system parameters so that the therapy can be personalized. This system identification is performed many times by measuring drug concentrations in plasma. The objective of this work is to provide an irregular sampling strategy that minimizes the uncertainty about the system parameters with a fixed amount of samples (cost constrained). We use Monte Carlo simulations to estimate the average Fisher's information matrix associated to the PK problem, and then estimate the sampling points that minimize the maximum uncertainty associated to system parameters (a minimax criterion). The minimization is performed employing a genetic algorithm. We show that such a sampling scheme can be designed in a way that is adapted to a particular patient and that it can accommodate any dosing regimen as well as it allows flexible therapeutic strategies.

  6. Pharmacokinetic Comparison of Berberine in Rat Plasma after Oral Administration of Berberine Hydrochloride in Normal and Post Inflammation Irritable Bowel Syndrome Rats

    Directory of Open Access Journals (Sweden)

    Zipeng Gong

    2014-01-01

    Full Text Available In the present study, post inflammation irritable bowel syndrome (PI-IBS rats were firstly established by intracolonic instillation of acetic acid with restraint stress. Then the pharmacokinetics of berberine in the rat plasma were compared after oral administration of berberine hydrochloride (25 mg/kg to normal rats and PI-IBS rats. Quantification of berberine in the rat plasma was achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were collected at 15 different points in time and the pharmacokinetic parameters were analyzed by WinNonlin software. Compared with the normal group, area under the plasma concentration vs. time curve from zero to last sampling time (AUC0–t and total body clearance (CL/F in the model group significantly increased or decreased, (2039.49 ± 492.24 vs. 2763.43 ± 203.14; 4999.34 ± 1198.79 vs. 3270.57 ± 58.32 respectively. The results indicated that the pharmacokinetic process of berberine could be altered in PI-IBS pathological conditions.

  7. Pharmacokinetics of tulathromycin in plasma and milk samples after a single subcutaneous injection in lactating goats (Capra hircus).

    Science.gov (United States)

    Grismer, B; Rowe, J D; Carlson, J; Wetzlich, S E; Tell, L A

    2014-04-01

    Eight adult female dairy goats received one subcutaneous administration of tulathromycin at a dosage of 2.5 mg/kg body weight. Blood and milk samples were assayed for tulathromycin and the common fragment of tulathromycin, respectively, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of tulathromycin was analyzed by a noncompartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single-dose administration of tulathromycin were as follows: C(max) (121.54 ± 19.01 ng/mL); T(max) (12 ± 12-24 h); area under the curve AUC(0→∞) (8324.54 ± 1706.56 ng·h/mL); terminal-phase rate constant λz (0.01 ± 0.002 h⁻¹); and terminal-phase rate constant half-life t1/2λz (67.20 h; harmonic). Mean milk pharmacokinetic parameters (±SD) following 45 days of sampling were as follows: Cmax (1594 ± 379.23 ng/mL); Tmax (12 ± 12-36 h); AUC(0→∞) (72,250.51 ± 18,909.57 ng·h/mL); λz (0.005 ± 0.001 h⁻¹); and t(1/2λz) (155.28 h; harmonic). All goats had injection-site reactions that diminished in size over time. The conclusions from this study were that tulathromycin residues are detectable in milk samples from adult goats for at least 45 days following subcutaneous administration, this therapeutic option should be reserved for cases where other treatment options have failed, and goat milk should be withheld from the human food chain for at least 45 days following tulathromycin administration.

  8. Add-in macros for rapid and versatile calculation of non-compartmental pharmacokinetic parameters on Microsoft Excel spreadsheets.

    Science.gov (United States)

    Sato, H; Sato, S; Wang, Y M; Horikoshi, I

    1996-06-01

    We developed a package of macro programs (named PK_MOMENT) to automatically calculate non-compartmental pharmacokinetic parameters on Microsoft Excel spreadsheets. These macros include rigorous algorithms to execute moment calculations in a comprehensive manner. An optimum number of terminal data points for infinite-time extrapolation can be calculated with one of these macros so that automatic calculation of infinite moment parameters is possible. The moment calculation with PK_MOMENT provided satisfactory results using the hybrid (mixed linear-logarithmic) trapezoidal method rather than the conventional linear trapezoidal method. The macro-aided pharmacokinetic analyses turned out to be useful in that the macro-containing cells can be easily copied and pasted to analyze other data sets and that powerful tools of Excel can be utilized. The use of our macros will be significantly time-saving for routine pharmacokinetic analyses, considering that pharmacokinetic data are usually stored in a spreadsheet format, typically with Excel.

  9. Population plasma and urine pharmacokinetics of ivabradine and its active metabolite S18982 in healthy Korean volunteers.

    Science.gov (United States)

    Choi, Hee Youn; Bae, Kyun-Seop; Cho, Sang-Heon; Ghim, Jong-Lyul; Choe, Sangmin; Jung, Jin Ah; Lim, Hyeong-Seok

    2016-04-01

    Ivabradine, a selective inhibitor of the pacemaker current (If ), is used for heart failure and coronary heart disease and is mainly metabolized to S18982. The purpose of this study was to explore the pharmacokinetics (PK) of ivabradine and S18982 in healthy Korean volunteers. Subjects in a phase I study were randomized to receive 2.5, 5, or 10 mg of ivabradine administered every 12 hours for 4.5 days, and serial plasma and urine concentrations of ivabradine and S18982 were measured. The plasma PK of ivabradine was best described by a 2-compartment model with mixed 0- and first-order absorption, linked to a 2-compartment model for S18982. The introduction of interoccasional variabilities and period as covariate into absorption-related parameters improved the model fit. Urine data have been applied to estimate renal and nonrenal clearance, enabling a more detailed description of the elimination process. We developed a population PK model describing the plasma and urine PK of ivabradine and S18982 in healthy Korean adult males. This model might be useful for predicting the plasma and urine PK of ivabradine, potentially helping to identify the optimal dosing regimens in various clinical situations.

  10. Saliva versus Plasma for Pharmacokinetic and Pharmacodynamic Studies of Fentanyl in Patients with Cancer.

    Science.gov (United States)

    Bista, Sudeep R; Haywood, Alison; Norris, Ross; Good, Phillip; Tapuni, Angela; Lobb, Michael; Hardy, Janet

    2015-11-01

    Fentanyl is widely used to relieve cancer pain. However there is great interpatient variation in the dose required to relieve pain and little knowledge about the pharmacokinetic and pharmacodynamic (PK/PD) relationship of fentanyl and pain control. Patients with cancer are fragile and there is reluctance on the part of health professionals to take multiple plasma samples for PK/PD studies. The relationship between plasma and saliva fentanyl concentrations was investigated to determine whether saliva could be a valid substitute for plasma in PK/PD studies. One hundred sixty-three paired plasma and saliva samples were collected from 56 patients prescribed transdermal fentanyl (Durogesic, Janssen-Cilag Pty Limited, NSW, Australia) at varying doses (12-200 µg/h). Pain scores were recorded at the time of sampling. Fentanyl and norfentanyl concentrations in plasma and saliva were quantified using HPLC-MS/MS. Saliva concentrations of fentanyl (mean = 4.84 μg/L) were much higher than paired plasma concentrations of fentanyl (mean = 0.877 μg/L). Both plasma and saliva mean concentrations of fentanyl were well correlated with dose with considerable interpatient variation at each dose. The relationship between fentanyl and norfentanyl concentrations was poor in both plasma and saliva. No correlation was observed between fentanyl concentration in plasma and saliva (r(2) = 0.3743) or free fentanyl in plasma and total saliva concentrations (r(2) = 0.1374). Pain scores and fentanyl concentration in either of the matrices were also not correlated. No predictive correlation was observed between plasma and saliva fentanyl concentration. However the detection of higher fentanyl concentrations in saliva than plasma, with a good correlation to dose, may allow saliva to be used as an alternative to plasma in PK/PD studies of fentanyl in patients with cancer. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

  11. Relative sensitivities of DCE-MRI pharmacokinetic parameters to arterial input function (AIF) scaling.

    Science.gov (United States)

    Li, Xin; Cai, Yu; Moloney, Brendan; Chen, Yiyi; Huang, Wei; Woods, Mark; Coakley, Fergus V; Rooney, William D; Garzotto, Mark G; Springer, Charles S

    2016-08-01

    Dynamic-Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) has been used widely for clinical applications. Pharmacokinetic modeling of DCE-MRI data that extracts quantitative contrast reagent/tissue-specific model parameters is the most investigated method. One of the primary challenges in pharmacokinetic analysis of DCE-MRI data is accurate and reliable measurement of the arterial input function (AIF), which is the driving force behind all pharmacokinetics. Because of effects such as inflow and partial volume averaging, AIF measured from individual arteries sometimes require amplitude scaling for better representation of the blood contrast reagent (CR) concentration time-courses. Empirical approaches like blinded AIF estimation or reference tissue AIF derivation can be useful and practical, especially when there is no clearly visible blood vessel within the imaging field-of-view (FOV). Similarly, these approaches generally also require magnitude scaling of the derived AIF time-courses. Since the AIF varies among individuals even with the same CR injection protocol and the perfect scaling factor for reconstructing the ground truth AIF often remains unknown, variations in estimated pharmacokinetic parameters due to varying AIF scaling factors are of special interest. In this work, using simulated and real prostate cancer DCE-MRI data, we examined parameter variations associated with AIF scaling. Our results show that, for both the fast-exchange-limit (FXL) Tofts model and the water exchange sensitized fast-exchange-regime (FXR) model, the commonly fitted CR transfer constant (K(trans)) and the extravascular, extracellular volume fraction (ve) scale nearly proportionally with the AIF, whereas the FXR-specific unidirectional cellular water efflux rate constant, kio, and the CR intravasation rate constant, kep, are both AIF scaling insensitive. This indicates that, for DCE-MRI of prostate cancer and possibly other cancers, kio and kep may be more suitable imaging

  12. Relative sensitivities of DCE-MRI pharmacokinetic parameters to arterial input function (AIF) scaling

    Science.gov (United States)

    Li, Xin; Cai, Yu; Moloney, Brendan; Chen, Yiyi; Huang, Wei; Woods, Mark; Coakley, Fergus V.; Rooney, William D.; Garzotto, Mark G.; Springer, Charles S.

    2016-08-01

    Dynamic-Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) has been used widely for clinical applications. Pharmacokinetic modeling of DCE-MRI data that extracts quantitative contrast reagent/tissue-specific model parameters is the most investigated method. One of the primary challenges in pharmacokinetic analysis of DCE-MRI data is accurate and reliable measurement of the arterial input function (AIF), which is the driving force behind all pharmacokinetics. Because of effects such as inflow and partial volume averaging, AIF measured from individual arteries sometimes require amplitude scaling for better representation of the blood contrast reagent (CR) concentration time-courses. Empirical approaches like blinded AIF estimation or reference tissue AIF derivation can be useful and practical, especially when there is no clearly visible blood vessel within the imaging field-of-view (FOV). Similarly, these approaches generally also require magnitude scaling of the derived AIF time-courses. Since the AIF varies among individuals even with the same CR injection protocol and the perfect scaling factor for reconstructing the ground truth AIF often remains unknown, variations in estimated pharmacokinetic parameters due to varying AIF scaling factors are of special interest. In this work, using simulated and real prostate cancer DCE-MRI data, we examined parameter variations associated with AIF scaling. Our results show that, for both the fast-exchange-limit (FXL) Tofts model and the water exchange sensitized fast-exchange-regime (FXR) model, the commonly fitted CR transfer constant (Ktrans) and the extravascular, extracellular volume fraction (ve) scale nearly proportionally with the AIF, whereas the FXR-specific unidirectional cellular water efflux rate constant, kio, and the CR intravasation rate constant, kep, are both AIF scaling insensitive. This indicates that, for DCE-MRI of prostate cancer and possibly other cancers, kio and kep may be more suitable imaging

  13. Pharmacokinetic study of schisandrin, schisandrol B, schisantherin A, deoxyschisandrin, and schisandrin B in rat plasma after oral administration of Shengmaisan formula by UPLC-MS.

    Science.gov (United States)

    Sun, Hui; Wu, Fangfang; Zhang, Aihua; Wei, Wenfeng; Han, Ying; Wang, Xijun

    2013-02-01

    Shengmaisan (SMS) is a traditional Chinese medicine prescription widely used for the treatment of cardiovascular diseases in Asia. Its lignans are major components responsible for therapeutic action. A rapid and specific UPLC-Q-TOF/MS has been developed and validated for simultaneous quantification of the five main bioactive components, i.e. schisandrin, schisandrol B, schisantherin A, deoxyschisandrin, and schisandrin B, in rat plasma after oral administration of SMS. All calibration curves showed excellent linearity within the test ranges. Validation proved the repeatability of the method was good and recovery was satisfactory. The separation of these compounds was carried out on a Waters ACQUITY HSS T(3) column (2.1 × 100 mm, 1.8 μm) by linear gradient elution using a mobile phase consisting of 0.01% formic acid in water and ACN containing 0.01% formic acid. In this work, plasma pharmacokinetic characteristics of lignans components after oral administration SMS were investigated using UPLC-Q-TOF/MS method. MS was performed on a Waters Micromass high-definition technology with an ESI source. Data were analyzed and estimated by compartmental methods and pharmacokinetic parameters calculated using WinNonlin Professional version 6.1. Results demonstrated that the proposed UPLC-Q-TOF/MS method was successfully applied to pharmacokinetic study of all components in rat plasma after oral administration of the SMS.

  14. High-performance liquid chromatographic assay for metamizol metabolites in rat plasma: application to pharmacokinetic studies.

    Science.gov (United States)

    Domínguez-Ramírez, Adriana Miriam; Calzadilla, Patricia Carrillo; Cortés-Arroyo, Alma Rosa; Hurtado Y de la Peña, Marcela; López, José Raúl Medina; Gómez-Hernández, Martín; López-Muñoz, Francisco Javier

    2012-12-01

    In order to evaluate the pharmacokinetics of metamizol in the presence of morphine in arthritic rats, after subcutaneous administration of the drugs, an easy, rapid, sensitive and selective analytical method was proposed and validated. The four main metamizol metabolites (4-methylaminoantipyrine, 4-aminoantipyrine, 4-acetylaminoantipyrine and 4-formylaminoantipyrine) were extracted from plasma samples (50-100μl) by a single solid-phase extraction method prior to reverse-phase high performance liquid chromatography with diode-array detection. Standard calibration graphs for all metabolites were linear within a range of 1-100μg/ml (r(2)≥0.99). The intra-day coefficients of variation (CV) were in the range of 1.3-8.4% and the inter-day CV ranged from 1.5 to 8.4%. The intra-day assay accuracy was in the range of 0.6-9.6% and the inter-day assay accuracy ranged from 0.9 to 7.5% of relative error. The lower limit of quantification was 1μg/ml for all metabolites using a plasma sample of 100μl. Plasma samples were stable at least for 4 weeks at -20°C. This method was found to be suitable for studying metamizol metabolites pharmacokinetics in arthritic rats, after simultaneous administration of metamizol and morphine, in single dose. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Determination and pharmacokinetic study of catechin in rat plasma by HPLC

    Institute of Scientific and Technical Information of China (English)

    Li Xie; Xin-Nan Li; De-Xi Jiang; Dan Zhang

    2011-01-01

    A high performance liquid chromatographic method was developed and validated for the quantitative determination of catechin in rat plasma and its pharmacokinetic study after intragastric administration of Catechu and Xiongdanjiangre Wan into SD rats. Plasma samples were prepared by protein precipitation using methanol-5% aqueous zinc sulfate (70:30, v/v) as precipitant. Chromatographic separation was achieved on Hypersil Cl8 column (250 mm~ 4.6 mm, 10 pm) with acetonitrile-water-triethylamine (6:94:0.3, v/v/v, pH 4.0+0.1, adjusted with phos- phoric acid) as mobile phase, followed by a UV detection at 207 nm. Good linearity was obtained over the range of 0.143-7.15 mg/L of catechin, with correlation coefficient of 0.9992. The method was simple, sensitive, accurate and reproducible and' has been successfully applied to the pharmacokinetic study of catechin in rat plasma.

  16. Enantioselective analysis of etodolac in human plasma by LC-MS/MS: Application to clinical pharmacokinetics.

    Science.gov (United States)

    de Miranda Silva, Carolina; Rocha, Adriana; Tozatto, Eduardo; da Silva, Lucienir Maria; Donadi, Eduardo Antônio; Lanchote, Vera Lucia

    2016-02-20

    Etodolac is a non-steroidal anti-inflammatory drug with preferential inhibition of cyclooxigenase-2 and is widely used in the management of pain in patients with inflammatory arthritis. Etodolac is available as a racemic mixture of (-)-(R)-Etodolac and (+)-(S)-Etodolac; cyclooxigenases inhibition is attributed to (+)-(S)-Etodolac. According to our knowledge, this is the first method for determination of etodolac enantiomers in plasma using LC-MS/MS. Plasma extraction were performed with 25μL of plasma and 1mL of n-hexane:ethyl acetate (95:5); racemic ibuprofen was used as internal standard. Resolution of enantiomers were performed in a Chiralcel(®)OD-H column; deprotonated [M-H](-) and their respective ion products were monitored at transitions of 286>242 for etodolac enantiomers and 205>161 for ibuprofen. The quantitation limit was 3.2ng/mL for both enantiomers in plasma. The method was applied to study the pharmacokinetics of etodolac enantiomers after the administration of a 300 and 400mg dose of racemic drug to a healthy volunteer. Analysis of plasma samples showed higher plasma concentration of (-)-(R)-Etodolacfor both doses (300mg dose: AUC(0-∞)49.80 versus 4.55ugh/mL;400mg dose: AUC(0-∞) 63.90 versus 6.00ugh/mL) with an (R)-(+)/(S)-(-) ratio of approximately 11.

  17. Enzyme-inducing anticonvulsants increase plasma clearance of dexmedetomidine: a pharmacokinetic and pharmacodynamic study.

    Science.gov (United States)

    Flexman, Alana M; Wong, Harvey; Riggs, K Wayne; Shih, Tina; Garcia, Paul A; Vacas, Susana; Talke, Pekka O

    2014-05-01

    Dexmedetomidine is useful during mapping of epileptic foci as it facilitates electrocorticography unlike most other anesthetic agents. Patients with seizure disorders taking enzyme-inducing anticonvulsants appear to be resistant to its sedative effects. The objective of the study was to compare the pharmacokinetic and pharmacodynamic profile of dexmedetomidine in healthy volunteers with volunteers with seizure disorders receiving enzyme-inducing anticonvulsant medications. Dexmedetomidine was administered using a step-wise, computer-controlled infusion to healthy volunteers (n = 8) and volunteers with seizure disorders (n = 8) taking phenytoin or carbamazapine. Sedation and dexmedetomidine plasma levels were assessed at baseline, during the infusion steps, and after discontinuation of the infusion. Sedation was assessed by using the Observer's Assessment of Alertness/Sedation Scale, Ramsay Sedation Scale, and Visual Analog Scale and processed electroencephalography (entropy) monitoring. Pharmacokinetic analysis was performed on both groups, and differences between groups were determined using the standard two-stage approach. A two-compartment model was fit to dexmedetomidine concentration-time data. Dexmedetomidine plasma clearance was 43% higher in the seizure group compared with the control group (42.7 vs. 29.9 l/h; P = 0.007). In contrast, distributional clearance and the volume of distribution of the central and peripheral compartments were similar between the groups. No difference in sedation was detected between the two groups during a controlled range of target plasma concentrations. This study demonstrates that subjects with seizure disorders taking enzyme-inducing anticonvulsant medications have an increased plasma clearance of dexmedetomidine as compared with healthy control subjects.

  18. Plasma and tissue pharmacokinetics of marbofloxacin in experimentally infected chickens with Mycoplasma gallisepticum and Escherichia coli.

    Science.gov (United States)

    Ding, H; Wang, L; Shen, X; Gu, X; Zeng, D; Zeng, Z

    2013-10-01

    The plasma and tissue pharmacokinetics of marbofloxacin in chickens experimentally infected with Mycoplasma gallisepticum and Escherichia coli were studied. Marbofloxacin was given to 66 infected chickens by oral administration at a dosage of 5 mg/kg b.w., once a day for three days. Plasma, brain, kidney, liver, lung, muscle and trachea were collected and marbofloxacin concentrations were analyzed by a high performance liquid chromatography method. In the infected chickens, maximal marbofloxacin concentrations in plasma, brain, kidney, liver, lung, muscle and trachea were 1.84, 1.33, 7.35, 5.61, 3.12, 2.98, and 4.51 g/mL (g); the elimination half-lives of marbofloxacin were 6.8, 2.74, 9.31, 8.45, 9.55, 11.53 and 5.46 h for plasma, brain, kidney, liver, lung, muscle and trachea, respectively. AUC were calculated to be 9.68, 8.04, 45.1, 27.03, 20.56, 19.47, and 32.68 μg/mL (g) for plasma, brain, kidney, liver, lung, muscle and trachea, respectively. Marbofloxacin concentration in tissues except for brain exceeded marbofloxacin concentration in plasma, with AUC(tissue) /AUC(plasma) ranging from 2.01 to 4.66 and Peak(tissue) /Peak(plasma) ranging from 1.62 to 3.99. The results showed that a marbofloxacin dosage of 5 mg/kg administered orally at 24 h intervals may provide successful treatment of chicken with MG and E. coli infection.

  19. Full-direct method for imaging pharmacokinetic parameters in dynamic fluorescence molecular tomography

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Guanglei, E-mail: guangleizhang@bjtu.edu.cn [Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084 (China); Department of Biomedical Engineering, School of Computer and Information Technology, Beijing Jiaotong University, Beijing 100044 (China); Pu, Huangsheng; Liu, Fei; Bai, Jing [Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084 (China); He, Wei [China Institute of Sport Science, Beijing 100061 (China); Luo, Jianwen, E-mail: luo-jianwen@tsinghua.edu.cn [Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084 (China); Center for Biomedical Imaging Research, School of Medicine, Tsinghua University, Beijing 100084 (China)

    2015-02-23

    Images of pharmacokinetic parameters (also known as parametric images) in dynamic fluorescence molecular tomography (FMT) can provide three-dimensional metabolic information for biological studies and drug development. However, the ill-posed nature of FMT and the high temporal variation of fluorophore concentration together make it difficult to obtain accurate parametric images in small animals in vivo. In this letter, we present a method to directly reconstruct the parametric images from the boundary measurements based on hybrid FMT/X-ray computed tomography (XCT) system. This method can not only utilize structural priors obtained from the XCT system to mitigate the ill-posedness of FMT but also make full use of the temporal correlations of boundary measurements to model the high temporal variation of fluorophore concentration. The results of numerical simulation and mouse experiment demonstrate that the proposed method leads to significant improvements in the reconstruction quality of parametric images.

  20. Full-direct method for imaging pharmacokinetic parameters in dynamic fluorescence molecular tomography

    Science.gov (United States)

    Zhang, Guanglei; Pu, Huangsheng; He, Wei; Liu, Fei; Luo, Jianwen; Bai, Jing

    2015-02-01

    Images of pharmacokinetic parameters (also known as parametric images) in dynamic fluorescence molecular tomography (FMT) can provide three-dimensional metabolic information for biological studies and drug development. However, the ill-posed nature of FMT and the high temporal variation of fluorophore concentration together make it difficult to obtain accurate parametric images in small animals in vivo. In this letter, we present a method to directly reconstruct the parametric images from the boundary measurements based on hybrid FMT/X-ray computed tomography (XCT) system. This method can not only utilize structural priors obtained from the XCT system to mitigate the ill-posedness of FMT but also make full use of the temporal correlations of boundary measurements to model the high temporal variation of fluorophore concentration. The results of numerical simulation and mouse experiment demonstrate that the proposed method leads to significant improvements in the reconstruction quality of parametric images.

  1. Solid state NMR and bioequivalence comparison of the pharmacokinetic parameters of two formulations of clindamycin

    KAUST Repository

    Al-Talla, Zeyad

    2011-01-01

    Objective: The purpose of this study was to compare the pharmacokinetic parameters and determine the bioequivalence of a generic formulation of clindamycin that is sold in the local markets in the Middle East (Clindox® 150 mg capsule; test) with a reference formulation (Dalacin C® 150 mg capsule) in healthy adult male volunteers. Methods: A single-dose, open-label, 2-period crossover study was conducted. Healthy male volunteers were randomly assigned to oral administration of a single treatment of the reference and test formulations. The same groups were given the alternate formulation. After dosing, serial blood samples were withdrawn for a period of 24 h. Serum harvested from the blood samples was analyzed for clindamycin by high performance liquid chromatography (HPLC) with ultraviolet detection. Pharmacokinetic parameters, including AUC0-∞, AUC 0-t, Cmax, Ke, tmax and t 1/2 were determined from the serum concentrations for both formulations (test and reference). The products were tested for bioequivalence after log-transformation of the data. Results: 24 healthy adult male volunteers from Jordan (mean [SD] age, 28.8 (7.7) years (range 19-45 years); height, 175.8 (10.6) cm (range 159.0-192.0 cm); weight, 75.6 (11.0) kg (range 58-101 kg); and body mass index, 24.4 (1.8) kg/m2 (range 21.3-28 kg/m2)) were enrolled in and completed the study. The 13C NMR spectra for both Dalacin C® and Clindox® showed 18 distinct lines associated with the 18 different carbon atoms. Conclusion: The statistical comparison suggested that Clindox® capsules are bioequivalent to Dalacin C® capsules. The 13C CPMAS results confirmed that the two drugs exhibit typical clindamycin spectra. ©2011 Dustri-Verlag Dr. K. Feistle.

  2. The effect of breed and sex on sulfamethazine, enrofloxacin, fenbendazole and flunixin meglumine pharmacokinetic parameters in swine.

    Science.gov (United States)

    Howard, J T; Baynes, R E; Brooks, J D; Yeatts, J L; Bellis, B; Ashwell, M S; Routh, P; O'Nan, A T; Maltecca, C

    2014-12-01

    Drug use in livestock has received increased attention due to welfare concerns and food safety. Characterizing heterogeneity in the way swine populations respond to drugs could allow for group-specific dose or drug recommendations. Our objective was to determine whether drug clearance differs across genetic backgrounds and sex for sulfamethazine, enrofloxacin, fenbendazole and flunixin meglumine. Two sires from each of four breeds were mated to a common sow population. The nursery pigs generated (n = 114) were utilized in a random crossover design. Drugs were administered intravenously and blood collected a minimum of 10 times over 48 h. A non-compartmental analysis of drug and metabolite plasma concentration vs. time profiles was performed. Within-drug and metabolite analysis of pharmacokinetic parameters included fixed effects of drug administration date, sex and breed of sire. Breed differences existed for flunixin meglumine (P-value<0.05; Cl, Vdss ) and oxfendazole (P-value<0.05, AUC0→∞ ). Sex differences existed for oxfendazole (P-value < 0.05; Tmax ) and sulfamethazine (P-value < 0.05, Cl). Differences in drug clearance were seen, and future work will determine the degree of additive genetic variation utilizing a larger population.

  3. Neural network modelling of antifungal activity of a series of oxazole derivatives based on in silico pharmacokinetic parameters

    Directory of Open Access Journals (Sweden)

    Kovačević Strahinja Z.

    2013-01-01

    Full Text Available In the present paper, the antifungal activity of a series of benzoxazole and oxazolo[ 4,5-b]pyridine derivatives was evaluated against Candida albicans by using quantitative structure-activity relationships chemometric methodology with artificial neural network (ANN regression approach. In vitro antifungal activity of the tested compounds was presented by minimum inhibitory concentration expressed as log(1/cMIC. In silico pharmacokinetic parameters related to absorption, distribution, metabolism and excretion (ADME were calculated for all studied compounds by using PreADMET software. A feedforward back-propagation ANN with gradient descent learning algorithm was applied for modelling of the relationship between ADME descriptors (blood-brain barrier penetration, plasma protein binding, Madin-Darby cell permeability and Caco-2 cell permeability and experimental log(1/cMIC values. A 4-6-1 ANN was developed with the optimum momentum and learning rates of 0.3 and 0.05, respectively. An excellent correlation between experimental antifungal activity and values predicted by the ANN was obtained with a correlation coefficient of 0.9536. [Projekat Ministarstva nauke Republike Srbije, br. 172012 i br. 172014

  4. Study on the pharmacokinetics of tea polyphenols injection in rat plasma

    Institute of Scientific and Technical Information of China (English)

    FU Ting; LIANG Jun; HAN Guo-zhu; L(U) Li; LI Nan

    2008-01-01

    Objective To study pharmacokinetics of the main active ingredients (-) Epigallocatechin-3-gallate (EGCG) and (-) Epicatechin-3-gallate (ECG) of tea polyphenols (TP) injection in rats. Methods EGCG and ECG in rat plasma were analyzed by reversed-phase HPLC, by which EGCG and ECG were eluted from a Kromasil C18 column with a linear gradient mobile phase consisting of CH3CN -0.1% citric acid at a gradient flow rate of 1.0-1.5 mL·min-1 and monitored at a wavelength of 280 nm. Fifteen rats were randomly divided into 3 groups of 5 animals receiving iv administration of TP injection, formulated with catechins-containing extract from green tea, at doses of 150,100 and 50 mL·min-1, respectively. Blood samples were collected pre-dosing and 2, 5, 10, 20, 40, 60, 90, 120,180,240,300 min postdosing. Aliquots of obtained plasma (200 μL) were cleaned up by liquid-liquid extraction with double volumes of EtoAe and were reconstituted with 100 μL of 10 96 CH3CN aqueous solution before injecting to chromatograph. Results The time course of EGCG and ECG concentrations in rat plasma decayed in a biexponential fashion. Their iv pharmacokinetics could be described by the two-compartment model and first-order kinetics with t1/2β 112.39-145.20 min and 46.63-61.48 min, Vd 6.28-7.96 L·kg-1 and 0.90-1.22 L·kg-1, CL 0.034-0.044 L·kg-1·min-1 and 0.010-0.015 L·kg-1·min-1 for EGCG and ECG, respectively. Conclusions The EGCG and ECG in plasma of rats administered i. v. TP injection pharmacokinetically behaved with linear kinetics over dose range studied. The two catechin derivatives undergo rapid elimination from rat body. As compared with ECG, EGCG eliminates at a relatively slow rate, and is distributed very widely with a Vd greatly exceeding the volume of total body water, suggesting that EGCG is likely to enter the tissue cells or strongly bind to some tissues to exert its potent antioxidant effects.The aforementioned characteristics of EGCG may be due to its high lipophilicity.

  5. Parameters of atmospheric plasmas produced by electrosurgical devices

    Science.gov (United States)

    Keidar, Michael; Shashurin, Alexey; Canady, Jerome

    2013-10-01

    Electrosurgical systems are extensively utilized in general surgery, surgical oncology, plastic and reconstructive surgery etc. In this work we study plasma parameters created by electrosurgical system SS-200E/Argon 2 of US Medical Innovations. The maximal length of the discharge plasma column at which the discharge can be sustained was determined as function of discharge power and argon flow rate. Electrical parameters including discharge current and voltage were measured. Recently proposed Rayleigh microwave scattering method for temporally resolved density measurements of small-size atmospheric plasmas was utilized. Simultaneously, evolution of plasma column was observed using intensified charge-coupled device (ICCD) camera.

  6. Determination of robust ocular pharmacokinetic parameters in serum and vitreous humor of albino rabbits following systemic administration of ciprofloxacin from sparse data sets by using IT2S, a population pharmacokinetic modeling program.

    Science.gov (United States)

    Drusano, G L; Liu, W; Perkins, R; Madu, A; Madu, C; Mayers, M; Miller, M H

    1995-08-01

    Robust determination of the concentration-time profile of anti-infective agents in certain specialized compartments is often limited by the inability to obtain more than a single sample from such a site in any one subject. Vitreous humor and cerebrospinal fluid are obvious examples for which the determination of concentrations of anti-infective agents is limited. Advances in pharmacodynamics have pointed out the importance of understanding the profiles of drugs in the plasma and in specialized compartments in order to dose the drugs to obtain the best patient outcomes. Advances in population pharmacokinetic modeling hold the promise of allowing proper estimation of drug penetration into the vitreous (or other specialized compartment) with only a single vitreous sample, in conjunction with plasma sampling. We have developed a rabbit model which allows multiple samples of vitreous to be obtained without breaking down the blood-vitreous barrier. We have employed this model to test the hypothesis that robust estimates of vitreous penetration by the fluoroquinolone ciprofloxacin can be obtained from a traditional intensive plasma sampling set plus a single vitreous sample. We studied 33 rabbits which were receiving 40 mg of ciprofloxacin per kg of body weight intravenously as short infusions and from which multiple plasma and vitreous samples were obtained and assayed for ciprofloxacin content by high-performance liquid chromatography. Data were analyzed by the iterative two-stage population modeling technique (IT2S), employing the iterative two-stage program of Forrest et al. (Antimicrob. Agents Chemother. 37:1065-1072, 1993). Two data sets were analyzed: all plasma and vitreous samples versus all plasma samples and the initially obtained single vitreous sample. The pharmacokinetic parameter values identified were used to calculate the percent vitreous penetration as the ratio of the area under the concentration-time curve for the vitreous to that for the plasma. The

  7. Penentuan Efektifitas Oksitetrasiklin Melalui Parameter Farmakokinetik/farmakodinamik pada Plasma dan Jaringan Ayam Broiler

    Directory of Open Access Journals (Sweden)

    Agustina Dwi Wijayanti

    2010-06-01

    Full Text Available A study was conducted to determine the effectiveness of oxytetracycline on the basis of itspharmacokinetic/pharmacodynamic (PK/PD parameters in the plasma and tissues of broiler following a50 mg/kg single dose of intravenous administration. The male broiler were injected with oxytetracycline attarsal medial venous. The blood, liver, kidney and abdominal muscle were collected at 14 points of timesamplings. Blood was centrifuged to obtain plasma and all tissues were extracted with Mc Ilvine buffer.Drug concentration in samples was determined by High Performance Liquid Chromatography (HPLCusing AOAC standard reference for tetracycline. The pharmacokinetic parameters of oxytetracycline werecalculated using non compartment method. The results were as follows. For plasma: the AUC was 790,615,5 ?g/mL minute , Clearance was 63,242 mL/min/kg bb, Tmax/Cmax was 1 minute/0,7 ?g/mL, T1/2elimination was 6,4, hours, Vd was 37 L/kg. For liver ; AUC was 36418,89, minute , Tmax/Cmax was 16hours/17,15 ?g/g, and T1/2 elimination was 24,5, hours. For kidney; AUC6808,41 ?g/g minute , Tmax/Cmax 1 minute/16,73 ?g/g, , T1/2 elimination was 11,55 hours. For muscle; AUC was 3502 ?g/g minute,Tmax/Cmax was 1 minute/2,58 ?g/g, T1/2 elimination was 167,39 hours. The ratio of AUC/MIC inplasma and tissues appeared to a good pharmacokinetic/pharmacodynamic parameter to determine theeffectiveness of oxytetracycline.

  8. Rapid Determination of Imatinib in Human Plasma by Liquid Chromatography-Tandem Mass Spectrometry: Application to a Pharmacokinetic Study

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jeong Soo; Cho, Eun Gi; Huh, Wooseong; Ko, Jaewook; Jung, Jin Ah; Lee, Sooyoun [Samsung Medical Center, Seoul (Korea, Republic of)

    2013-08-15

    A simple, fast and robust analytical method was developed to determine imatinib in human plasma using liquid chromatography-tandem mass spectrometry with electrospray ionization in the positive ion mode. Imatinib and labeled internal standard were extracted from plasma with a simple protein precipitation. The chromatographic separation was performed using an isocratic elution of mobile phase involving 5.0 mM ammonium formate in water -5.0 mM ammonium formate in methanol (30:70, v/v) over 3.0 min on reversed-stationary phase. The detection was performed using a triple-quadrupole tandem mass spectrometer in multiple-reaction monitoring mode. The developed method was validated with lower limit of quantification of 10 ng/mL. The calibration curve was linear over 10-2000 ng/mL (R{sup 2} > 0.99). The method validation parameters met the acceptance criteria. The spiked samples and standard solutions were stable under conditions for storage and handling. The reliable method was successfully applied to real sample analyses and thus a pharmacokinetic study in 27 healthy Korean male volunteers.

  9. Use of trifluoroacetic acid to quantify small, polar compounds in rat plasma during discovery-phase pharmacokinetic evaluation.

    Science.gov (United States)

    Bock, M J; Neilson, K L; Dudley, A

    2007-09-01

    Although it is accepted that trifluoroacetic acid (TFA) can cause suppression of an analyte during LC/MS analysis, this paper presents a relatively sensitive gradient method that uses a TFA mobile phase for the improved quantification of small, polar drug-like compounds. The described method was developed in a discovery drug metabolism and pharmacokinetics (DMPK) laboratory for the screening measurement of compound concentrations to calculate PK parameters and CNS exposure of compounds from a chemical series that had poor chromatography under generic methods using formic acid mobile phase. The samples were collected by a Culex automated sampling unit, and the plasma proteins were precipitated by a Tecan robot in 96-well plates. After centrifugation, the supernatant was removed, dried down using a SPE-Dry unit, and the samples were reconstituted in aqueous buffer on the robot. The samples were analyzed on an Agilent LC/MSD using a 5-min gradient on a 5 cm phenyl column. No additional steps, such as the "TFA-fix", were necessary. Although sample batches were analyzed over 6h, no drift or degradation of signal was observed. The improved chromatography resulted in a method that was selective, rugged, and had a dynamic range from 5 to 20,000 nM, which was sufficient to quantitate low volume, serial plasma samples collected out to 8 h postdose.

  10. The use of in vitro metabolic parameters and physiologically based pharmacokinetic (PBPK) modeling to explore the risk assessment of trichloroethylene

    NARCIS (Netherlands)

    Hissink, E.M.; Bogaards, J.J.P.; Freidig, A.P.; Commandeur, J.N.M.; Vermeulen, N.P.E.; Bladeren, P.J. van

    2002-01-01

    A physiologically based pharmacokinetic (PBPK) model has been developed for trichloroethylene (1,1,2-trichloroethene, TRI) for rat and humans, based on in vitro metabolic parameters. These were obtained using individual cytochrome P450 and glutathione S-transferase enzymes. The main enzymes involved

  11. Determination and pharmacokinetic study of pirfenidone in rat plasma by UPLC-MS/MS.

    Science.gov (United States)

    Sun, Wei; Jiang, Zhe-li; Zhou, Lei; Chen, Rui-min; Wang, Zhe; Li, Wan-shu; Jiang, Shuo-min; Hu, Guo-xin; Chen, Rui-jie

    2015-02-15

    A rapid, sensitive and selective ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed and validated for the determination and pharmacokinetic investigation of pirfenidone in rat plasma. Sample preparation was accomplished through a simple one-step deproteinization procedure with 0.2 mL of acetonitrile to a 0.1 mL plasma sample. Plasma samples were separated by UPLC on an Acquity UPLC BEH C18 column using a mobile phase consisting of acetonitrile-0.1% formic acid in water with gradient elution. The total run time was 3.0 min and the elution of pirfenidone was at 1.39 min. The detection was performed on a triple quadrupole tandem mass spectrometer in the multiple reaction-monitoring (MRM) mode using the respective transitions m/z 186.2→92.1 for pirfenidone and m/z 237.1→194.2 for carbamazepine (IS), respectively. The calibration curve was linear over the range of 5-2000 ng/mL with a lower limit of quantitation (LLOQ) of 5 ng/mL. Mean recovery of pirfenidone in plasma was in the range of 80.4-84.3%. Intra-day and inter-day precision were both pirfenidone in rats.

  12. Effect of nitazoxanide on albendazole pharmacokinetics in cerebrospinal fluid and plasma in rats.

    Science.gov (United States)

    Ruiz-Olmedo, María Isabel; González-Hernández, Iliana; Palomares-Alonso, Francisca; Franco-Pérez, Javier; González F, María de Lourdes; Jung-Cook, Helgi

    2017-03-01

    Background: Although albendazole is the drug-of-choice for the treatment of neurocysticercosis, its efficacy is limited due to its low bioavailability. An alternative for optimizing pharmacological treatment is through drug combinations. In vitro studies have shown that nitazoxanide and tizoxanide (the active metabolite of nitazoxanide) exhibit cysticidal activity and that the combination of tizoxanide with albendazole sulfoxide (the active metabolite of albendazole) produced an additive effect. Objectives: (1) To assess the concentration profile of tizoxanide in plasma and in cerebrospinal fluid; and (2) to evaluate the influence of nitazoxanide on the pharmacokinetics of albendazole in plasma and in cerebrospinal fluid. Methods: Two different studies were conducted. In study 1, 10 male Sprague-Dawley rats received a single oral dose of 7.5 mg/kg of nitazoxanide and serial blood and cerebrospinal fluid samples were collected over a period of 4 h. In study 2, 38 healthy male Sprague-Dawley rats were randomly divided into two groups: one of these received a single dose of albendazole (15 mg/kg) and, in the other group, albendazole (15 mg/kg) was co-administered with nitazoxanide (7.5 mg/kg). Plasma and cerebrospinal fluid samples were collected from 0 to 16 h after administration. Albendazole sulfoxide and tizoxanide levels were assayed by using HPLC or LC/MS techniques. Results: In study 1, tizoxanide reached a maximum plasma concentration of 244.42 ± 31.98 ng/mL at 0.25 h; however, in cerebrospinal fluid, this could be detected only at 0.5 h, and levels were below the quantification limit (10 ng/mL). These data indicate low permeation of tizoxanide into the blood brain barrier. In study 2, Cmax, the area under the curve, and the mean residence time of albendazole sulfoxide in plasma and cerebrospinal fluid were not affected by co-administration with nitazoxanide. Conclusion: The results of the present study indicate that in rats at the applied doses

  13. Numerical Simulation of Basic Parameters in Plasma Spray

    Institute of Scientific and Technical Information of China (English)

    范群波; 王鲁; 王富耻

    2004-01-01

    On the basis of energy balance in the plasma gas, a new, simplified but effective mathematical model is developed to predict the temperature, velocity and ionization degrees of different species at the torch exit, which can be directly calculated just by inputting the general spraying parameters, such as current, voltage, flow rates of gases, etc. Based on this method, the effects of plasma current and the flow rate of Ar on the basic parameters at the torch exit are discussed. The results show that the temperature, velocity and ionization degrees of gas species will increase with increasing the plasma current; while increasing Ar flow rate can increase the velocity at the exit but decrease the temperature and ionization degrees of plasma species. The method would be helpful to predict the temperature and velocity fields in a plasma jet in future, and direct the practical plasma spray operations.

  14. Plasma parameters controlled by remote electron shower in a double plasma device

    Science.gov (United States)

    Mishra, M. K.; Phukan, A.

    2012-07-01

    The principal feature of this experiment is the electron showers consisting of three tungsten wires embedded by the plasma, which are heated up consequently emitting electrons inside the diffused plasma to control the plasma parameters in the discharge section of a double plasma device. These cold electrons emitted by the heated filament are free from maintenance of discharge which is sustained in the source section. The target plasma, where electrons are injected is produced as a result of diffusion from the source section. It is found that, plasma density and plasma potential can be effectively controlled in this way.

  15. The precision of pharmacokinetic parameters in dynamic contrast-enhanced magnetic resonance imaging: the effect of sampling frequency and duration

    Energy Technology Data Exchange (ETDEWEB)

    Aerts, Hugo J W L [Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht (Netherlands); Jaspers, K; Backes, Walter H, E-mail: w.backes@mumc.nl [Department of Radiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC), Maastricht (Netherlands)

    2011-09-07

    Dynamic contrast-enhanced magnetic resonance imaging is increasingly applied for tumour diagnosis and early evaluation of therapeutic responses over time. However, the reliability of pharmacokinetic parameters derived from DCE-MRI is highly dependent on the experimental settings. In this study, the effect of sampling frequency (f{sub s}) and duration on the precision of pharmacokinetic parameters was evaluated based on system identification theory and computer simulations. Both theoretical analysis and simulations showed that a higher value of the pharmacokinetic parameter K{sup trans} required an increasing sampling frequency. For instance, for similar results, a relatively low f{sub s} of 0.2 Hz was sufficient for a low K{sup trans} of 0.1 min{sup -1}, compared to a high f{sub s} of 3 Hz for a high K{sup trans} of 0.5 min{sup -1}. For the parameter v{sub e}, a decreasing value required a higher sampling frequency. A sampling frequency below 0.1 Hz systematically resulted in imprecise estimates for all parameters. For the K{sup trans} and v{sub e} parameters, the sampling duration should be above 2 min, but durations of more than 7 min do not further improve parameter estimates.

  16. The precision of pharmacokinetic parameters in dynamic contrast-enhanced magnetic resonance imaging: the effect of sampling frequency and duration

    Science.gov (United States)

    Aerts, Hugo J. W. L.; Jaspers, K.; Backes, Walter H.

    2011-09-01

    Dynamic contrast-enhanced magnetic resonance imaging is increasingly applied for tumour diagnosis and early evaluation of therapeutic responses over time. However, the reliability of pharmacokinetic parameters derived from DCE-MRI is highly dependent on the experimental settings. In this study, the effect of sampling frequency (fs) and duration on the precision of pharmacokinetic parameters was evaluated based on system identification theory and computer simulations. Both theoretical analysis and simulations showed that a higher value of the pharmacokinetic parameter Ktrans required an increasing sampling frequency. For instance, for similar results, a relatively low fs of 0.2 Hz was sufficient for a low Ktrans of 0.1 min-1, compared to a high fs of 3 Hz for a high Ktrans of 0.5 min-1. For the parameter ve, a decreasing value required a higher sampling frequency. A sampling frequency below 0.1 Hz systematically resulted in imprecise estimates for all parameters. For the Ktrans and ve parameters, the sampling duration should be above 2 min, but durations of more than 7 min do not further improve parameter estimates.

  17. Study of parameters of a facility generating compressive plasma flows

    Science.gov (United States)

    Leyvi, A. Ya

    2017-05-01

    The prosperity of plasma technologies stimulates making of a facility generating compressive plasma flows at the South Ural State University. The facility is a compact-geometry magnetoplasma compressor with the following parameters: stored energy up to 15 kJ, voltage of a bank from 3 to 5 kV; nitrogen, air, and other gases can serve as its operating gas. The investigation of parameters of the facility showed the following parameters of compressive plasma flows: impulse duration of up to 120 μs, discharge current of 50-120 kA, speed of plasma flow of 15-30 km/s. By contrast to the available facilities, the parameters of the developed facility can be adjusted in a wide range of voltage from 2 kV to 10 kV, its design permits generating CPF in horizontal and vertical positions.

  18. Collisionless expansion of pulsed radio frequency plasmas. II. Parameter study

    Science.gov (United States)

    Schröder, T.; Grulke, O.; Klinger, T.; Boswell, R. W.; Charles, C.

    2016-01-01

    The plasma parameter dependencies of the dynamics during the expansion of plasma are studied with the use of a versatile particle-in-cell simulation tailored to a plasma expansion experiment [Schröder et al., J. Phys. D: Appl. Phys. 47, 055207 (2014); Schröder et al., Phys. Plasmas 23, 013511 (2016)]. The plasma expansion into a low-density ambient plasma features a propagating ion front that is preceding a density plateau. It has been shown that the front formation is entangled with a wave-breaking mechanism, i.e., an ion collapse [Sack and Schamel, Plasma Phys. Controlled Fusion 27, 717 (1985); Sack and Schamel, Phys. Lett. A 110, 206 (1985)], and the launch of an ion burst [Schröder et al., Phys. Plasmas 23, 013511 (2016)]. The systematic parameter study presented in this paper focuses on the influence on this mechanism its effect on the maximum velocity of the ion front and burst. It is shown that, apart from the well known dependency of the front propagation on the ion sound velocity, it also depends sensitively on the density ratio between main and ambient plasma density. The maximum ion velocity depends further on the initial potential gradient, being mostly influenced by the plasma density ratio in the source and expansion regions. The results of the study are compared with independent numerical studies.

  19. Analysis of nabumetone in human plasma by HPLC. Application to single dose pharmacokinetic studies.

    Science.gov (United States)

    Kobylińska, Kamila; Barlińska, Małgorzata; Kobylińska, Maria

    2003-06-01

    A simple and sensitive high performance liquid chromatography method for the determination of nabumetone in human plasma is described. The procedure involves liquid-liquid extraction with ethyl acetate and reversed-phase chromatography with fluorimetric detection (excitation 230 nm, emission 356 nm). The chromatographic conditions and the extraction procedure gave a clean chromatogram for the compound. The limit of quantitation was established as 0.313 ng/ml and the calibration curve was linear up to 20 ng/ml. The within-day and between-day relative standard deviations were less than 10% and the accuracy of the assay was in the range of 99-104%. The suitability of the method is shown for pharmacokinetic studies.

  20. Herb drug interaction: effect of Manix® on pharmacokinetic parameters of pefloxacin in rat model

    Science.gov (United States)

    Odunke, Nduka Sunday; Eleje, Okonta; Christiana, Abba Chika; Peter, Ihekwereme Chibueze; Uchenna, Ekwedigwe; Matthew, Okonta

    2014-01-01

    Objective To evaluate the effect of Manix®, the commonly used polyherbal formulation on pefloxacin pharmacokinetic parameters. Methods Microbiological assay was employed using clinical isolate of Escherichia coli samples from hospitalized patients. Results Manix® altered the bioavailability parameters of pefloxacin as thus, maximal concentration (Cmax) of pefloxacin (0.91±0.31) µg/mL occurred at time to reach maximal concentration (tmax) 4.0 h while in the group that received Manix® alongside pefloxacin Cmax was (0.22±0.08) µg/mL at tmax 1.0 h respectively. The area under curve of pefloxacin alone was (7.83±5.14) µg/h/mL while with Manix® was (2.60±0.08) µg/h/mL. There was a significant difference between Cmax, tmax and area under curve between pefloxacin alone and pefloxacin after Manix® pre-treatment (P<0.05). Conclusions The concurrent use of Manix® and pefloxacin has been found to compromise the therapeutic effectiveness of pefloxacin which could lead to poor clinical outcomes in patients. PMID:25183119

  1. Plasma and cerebrospinal fluid concentrations of ibuprofen in pediatric patients and antipyretic effect: Pharmacokinetic-pharmacodynamic modeling analysis.

    Science.gov (United States)

    Har-Even, Ronly; Stepensky, David; Britzi, Malka; Soback, Stefan; Chaim, Adina Bar; Brandriss, Norit; Goldman, Michael; Berkovitch, Matitiahu; Kozer, Eran

    2014-09-01

    We aimed to determine the relationship between plasma and cerebrospinal fluid (CSF) concentrations of ibuprofen and the antipyretic effect in pediatric patients. A prospective cohort of infants and children aged 3 months to 15 years and treated with ibuprofen was studied. The patients received ibuprofen (via oral route, median dose of 10.0 mg/kg; 3.4-11.4 mg/kg range), samples of blood and CSF were collected, and body temperature was measured. Sequential analysis of the pharmacokinetic and pharmacodynamic data from 28 patients was performed using a population modeling approach. The observed concentration versus time data indicated substantial pharmacokinetic variability in absorption and distribution of ibuprofen between the patients. The pharmacokinetic modeling outcomes indicate that following a ∼25-minute lag time, ibuprofen is rapidly absorbed to the central compartment and rapidly equilibrates with the CSF, resulting in the total ibuprofen concentration in the CSF versus plasma (CCSF /Cplasma ) of 0.011 ± 0.007. The antipyretic effect of ibuprofen was best described by an indirect response PK-PD model incorporating patient baseline body temperature and ibuprofen concentration in the CSF. We conclude that the pharmacokinetic-pharmacodynamic modeling can be used to predict the time course of ibuprofen plasma and CSF concentrations and of the antipyretic effects in individual pediatric patients. © 2014, The American College of Clinical Pharmacology.

  2. [Study on compatibility of Salviae Miltiorrhizae Radix et Rhizoma and Chuanxiong Rhizoma based on pharmacokinetics of effective components salvianolic acid B and ferulic acid in rat plasma].

    Science.gov (United States)

    Zhang, Cui-ying; Zhang, Hong; Dong, Yu; Ren, Wei-guang; Chen, Heng-wen

    2015-04-01

    A study was made on the pharmacokinetic regularity of effective components salvianolic acid B and ferulic acid in Salviae Miltiorrhizae Radix et Rhizoma (SMRR) and Chuanxiong Rhizoma(CR) in rats, so as to discuss the compatibility mechanism of Salviae Miltiorrhizae Radix et Rhizoma and Chuanxiong Rhizoma. Rats were randomly divided into three groups and intravenously injected with 50 mg x kg(-1) salvianolic acid B for the single SMRR extracts group, 0.5 mg x kg(-1) ferulic acid for the single CR extracts group and 50 mg x kg(-1) salvianolic acid B + 0.5 mg x kg(-1) ferulic acid for the SMRR and CR combination group. The blood samples were collected at different time points and purified by liquid-liquid extraction with ethyl acetate. With chloramphenicol as internal standard (IS), UPLC was adopted to determine concentrations of salvianolic acid B and ferulic acid. The pharmacokinetic parameters of salvianolic acid B and ferulic acid were calculated with WinNonlin 6.2 software and analyzed by SPSS 19.0 statistical software. The UPLC analysis method was adopted to determine salvianolic acid B and ferulic acid in rat plasma, including linear equation, stability, repeatability, precision and recovery. The established sample processing and analysis methods were stable and reliable, with significant differences in major pharmacokinetic parameters, e.g., area under the curve (AUC), mean residence time (MRT) and terminal half-life (t(1/2)). According to the experimental results, the combined application of SMRR and CR can significantly impact the pharmacokinetic process of their effective components in rats and promote the wide distribution, shorten the action time and prolong the in vivo action time of salvianolic acid B and increase the blood drug concentration and accelerate the clearance of ferulic acid in vivo.

  3. Pooled population pharmacokinetic model of imipenem in plasma and the lung epithelial lining fluid

    Science.gov (United States)

    Rizk, Matthew L.; Lala, Mallika; Chavez‐Eng, Cynthia; Visser, Sandra A. G.; Kerbusch, Thomas; Danhof, Meindert; Rao, Gauri; van der Graaf, Piet H.

    2016-01-01

    Aims Several clinical trials have confirmed the therapeutic benefit of imipenem for treatment of lung infections. There is however no knowledge of the penetration of imipenem into the lung epithelial lining fluid (ELF), the site of action relevant for lung infections. Furthermore, although the plasma pharmacokinetics (PK) of imipenem has been widely studied, most studies have been based on selected patient groups. The aim of this analysis was to characterize imipenem plasma PK across populations and to quantify imipenem ELF penetration. Methods A population model for imipenem plasma PK was developed using data obtained from healthy volunteers, elderly subjects and subjects with renal impairment, in order to identify predictors for inter‐individual variability (IIV) of imipenem PK. Subsequently, a clinical study which measured plasma and ELF concentrations of imipenem was included in order to quantify lung penetration. Results A two compartmental model best described the plasma PK of imipenem. Creatinine clearance and body weight were included as subject characteristics predictive for IIV on clearance. Typical estimates for clearance, central and peripheral volume, and inter‐compartmental clearance were 11.5 l h–1, 9.37 l, 6.41 l, 13.7 l h–1, respectively (relative standard error (RSE) <8%). The distribution of imipenem into ELF was described using a time‐independent penetration coefficient of 0.44 (RSE 14%). Conclusion The identified lung penetration coefficient confirms the clinical relevance of imipenem for treatment of lung infections, while the population PK model provided insights into predictors of IIV for imipenem PK and may be of relevance to support dose optimization in various subject groups. PMID:26852277

  4. LC-MS/MS Determination and Pharmacokinetic Study of Dehydrocorydaline in Rat Plasma after Oral Administration of Dehydrocorydaline and Corydalis yanhusuo Extract

    Directory of Open Access Journals (Sweden)

    Qiu-Yue Li

    2014-10-01

    Full Text Available A rapid, sensitive and selective liquid chromatography/tandem mass spectrometry method (LC-MS/MS was developed and validated for determination of dehydrocorydaline (DHC in rat plasma using nitidine chloride as an internal standard. The analytes were solid-phase extracted and eluted on a C18 chromatography column using a mobile phase of acetonitrile and water (containing 0.8% formic acid and 10 mM ammonium acetate (28:72, v/v. Detection was performed using positive ion electrospray ionization in multiple reaction monitoring modes. The assay was linear over the concentration range 0.625–250 ng/mL with a quantification limit of 0.625 ng/mL. The precision was <13.7%, the accuracy >93.1%, and extraction recovery ranged from 92.1% to 107%. The validated method was successfully applied to the pharmacokinetics and excretion study of DHC in rat plasma after oral administration of pure DHC and an effective fraction of Corydalis yanhusuo (EFY. The pharmacokinetic parameters showed that DHC from EFY was absorbed more rapidly and eliminated more slowly than pure DHC. The result suggests that the differences might be due to the presence of P-glycoprotein (P-gp inhibitors and that other alkaloids co-existing in the EFY may compete with DHC for transportation by P-gp, metabolization by P450, and binding to plasma proteins.

  5. Development and validation of an UPLC-Q/TOF-MS assay for the quantitation of neopanaxadiol in beagle dog plasma: Application to a pharmacokinetic study.

    Science.gov (United States)

    Geng, Cong; Wang, Chun-Hong; Hu, Hong; Gao, Xiao-Ping; Gong, Ai-Hua; Lin, Ying-Wei; Fan, Xiu-Shuang; Li, Heng; Yin, Jian-Yuan

    2016-10-27

    Neopanaxadiol (NPD), the main panaxadiol constituent of Panax ginseng C. A. Meyer (Araliaceae), has been regarded as the active component for the treatment of Alzheimer's disease. However, few references are available about pharmacokinetic evaluation for NPD. Accordingly, a rapid and sensitive method for quantitative analysis of NPD in beagle dog plasma based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry was developed and validated. Analytes were extracted from plasma by liquid-liquid extraction and chromatographic separation was achieved on an Agilent Zorbax Stable Bond C18 column. Detection was performed in the positive ion mode using multiple reaction monitoring of the transitions both at m/z 461.4 → 425.4 for NPD and internal standard of panaxadiol. All validation parameters, such as lower limit of quantitation, linearity, specificity, precision, accuracy, extraction recovery, matrix effect and stability, were within acceptable ranges and the method was appropriate for multitude sample determination. After oral intake, NPD was slowly absorbed and eliminated from circulatory blood system and corresponding plasma exposure was low. Application of this quantitative method will yield the first pharmacokinetic profile after oral administration of NPD to beagle dog. The information obtained here will be useful to understand the pharmacological effects of NPD.

  6. Pharmacokinetic parameters and tissue distribution of magnetic Fe3O4 nanoparticles in mice

    Directory of Open Access Journals (Sweden)

    Jun Wang

    2010-10-01

    Full Text Available Jun Wang1, Yue Chen1, Baoan Chen1, Jiahua Ding1, Guohua Xia1, Chong Gao1, Jian Cheng1, Nan Jin1, Ying Zhou1, Xiaomao Li1, Meng Tang2, Xue Mei Wang21Department of Hematology, Zhongda Hospital, Clinical Medical School, Southeast University, Nanjing, People’s Republic of China; 1Department of Physics, University of Saarland, D-266041 Saarbruechen, Germany; 2National Key Laboratory of Bioelectronics (Chien-Shiung Wu Laboratory, Southeast University, Nanjing, People’s Republic of ChinaBackground: This study explored the pharmacokinetic parameters and tissue distribution of magnetic iron oxide nanoparticles (Fe3O4 MNPs in imprinting control region (ICR mice.Methods: The Fe3O4 MNPs were synthesized by chemical coprecipitation, and their morphology and appearance were observed by transmission electron microscopy. ICR mice were divided into a control group and a Fe3O4 MNP-treated group. Probable target organs in ICR mice were observed, and the pharmacokinetic parameters and biodistribution of Fe3O4 MNPs in tissues were identified using atomic absorption spectrophotometry.Results: Fe3O4 MNPs were spherical with a well distributed particle diameter, and were distributed widely in various target organs and tissues including the heart, liver, spleen, lungs, kidneys, brain, stomach, small intestine, and bone marrow. The majority of Fe3O4 MNPs were distributed to the liver and the spleen. Fe3O4 MNP levels in brain tissue were higher in the Fe3O4 MNP-treated group than in the control group, indicating that Fe3O4 MNPs can penetrate the blood–brain barrier.Conclusion: These results suggest that the distribution of Fe3O4 MNPs was mostly in the liver and spleen, so the curative effect of these compounds could be more pronounced for liver tumors. Furthermore, Fe3O4 MNPs might be used as drug carriers to overcome physiologic barriers.Keywords: magnetic nanoparticles, Fe3O4, tissue distribution, mice

  7. Study on plasma parameters and dust charging in an electrostatically plugged multicusp plasma device

    Science.gov (United States)

    Kakati, B.; Kausik, S. S.; Saikia, B. K.; Bandyopadhyay, M.

    2011-06-01

    The effect of the electrostatic confinement potential on the charging of dust grains and its relationship with the plasma parameters has been studied in an electrostatically plugged multicusp dusty plasma device. Electrostatic plugging is implemented by biasing the electrically isolated magnetic multicusp channel walls. The experimental results show that voltage applied to the channel walls can be a controlling parameter for dust charging.

  8. Determination of nimodipine in plasma by HPLC-MS/MS and pharmacokinetic application

    Directory of Open Access Journals (Sweden)

    Demétrius Fernandes do Nascimento

    2010-12-01

    Full Text Available To develop and validate a rapid, specific and highly sensitive method to quantify nimodipine in human plasma using dibucaine as the internal standard (IS. The analyte and IS were extracted from plasma samples by liquid-liquid extraction using hexane-ethyl acetate (1:1 v/v. The chromatographic separation was performed on a Varian® Polaris C18 analytical column (3 μm, 50 x 2.0 mm and pre-column SecurityguardTM C18 (4.0 x 3.0 mm with a mobile phase of Acetonitrile-Ammonium acetate 0.02 ml/L (80:20v/v. The method had a chromatographic run time of 4.5 min and linear calibration curve over the range of 0.1- 40 ng/mL (r > 0.9938. The limit of quantification was 100 pg/mL. Acceptable precision and accuracy were obtained for concentrations over the standard curve ranges. This validated method was successfully applied in determining the pharmacokinetic profile of nimodipine tablets of 30 mg administered to 24 healthy volunteers. The proposed method of analysis provided a sensitive and specific assay for nimodipine determination in human plasma. The time for the determination of one plasma sample was 4.5 min. This method is suitable for the analysis of nimodipine in human plasma samples collected for pharmacokinetic, bioavailability or bioequivalence studies in humans.Um método rápido, específico e sensível para quantificar nimodipino em plasma humano usando dibucaína como padrão interno (IS é descrito. O analito e o IS foram extraídos das amostras de plasma por extração líquido-líquido usando hexano-acetato de etila (1:1 v/v. A separação cromatográfica foi realizada utilizando-se uma coluna analítica C18 Varian® Polaris (3 μm, 50 x 2,0 mm e uma pré-coluna SecurityguardTM C18 (4,0 x 3,0 mm e acetonitrila-acetato de amônia 0,02 mol/L (80:20 v/v como fase móvel. O método apresentou tempo total de corrida de 4,5 min e curva de calibração linear com concentrações entre 0,1-40 ng/mL (r > 0,9938. O limite de quantificação foi de 100

  9. Rapid and sensitive ultra-high-pressure liquid chromatography method for quantification of antichagasic benznidazole in plasma: application in a preclinical pharmacokinetic study.

    Science.gov (United States)

    Davanço, Marcelo Gomes; de Campos, Michel Leandro; Peccinini, Rosângela Gonçalves

    2015-07-01

    Benznidazole (BNZ) and nifurtimox are the only drugs available for treating Chagas disease. In this work, we validated a bioanalytical method for the quantification of BNZ in plasma aimed at improving sensitivity and time of analysis compared with the assays already published. Furthermore, we demonstrated the application of the method in a preclinical pharmacokinetic study after administration of a single oral dose of BNZ in Wistar rats. A Waters® Acquity UHPLC system equipped with a UV-vis detector was employed. The method was established using an Acquity® UHPLC HSS SB C18 protected by an Acquity® UHPLC HSS SB C18 VanGuard guard column and detection at 324 nm. The mobile phase consisted of ultrapure water-acetonitrile (65:35), and elution was isocratic. The mobile phase flow rate was 0.55 mL/min, the volume of injection was 1 μL, and the run time was just 2 min. The samples were kept at 25°C until injection and the column at 45°C for the chromatographic separation. The sample preparation was performed by a rapid protein precipitation with acetonitrile. The linear concentration range was 0.15-20 µg/mL. The pharmacokinetic parameters of BNZ in rats were determined and the method was considered sensitive, fast and suitable for application in pharmacokinetic studies.

  10. Validation of a high-performance liquid chromatographic ultraviolet detection method for the quantification of vandetanib in rat plasma and its application to pharmacokinetic studies

    Directory of Open Access Journals (Sweden)

    Hongjun Lin

    2014-01-01

    Conclusion: A simple and sensitive HPLC assay with ultraviolet detection method was developed for the determination of vandetanib in rat plasma. This method is sufficient for pharmacokinetic studies of vandetanib in small animals and may be applied to human pharmacokinetic studies.

  11. Simultaneous determination of harpagoside and cinnamic acid in rat plasma by high-performance liquid chromatography: application to a pharmacokinetic study.

    Science.gov (United States)

    Li, Peifan; Zhang, Yunhui; Xiao, Li; Jin, Xinghua; Yang, Kun

    2007-12-01

    Radix Scrophulariae (xuanshen) is one of the famous Chinese herbal medicines widely used to treat rheumatism, tussis, pharyngalgia, arthritis, constipation, and conjunctival congestion. Harpagoside and cinnamic acid are the main bioactive components of xuanshen. The purpose of this study was to develop an HPLC-UV method for simultaneous determination of harpagoside and cinnamic acid in rat plasma and investigate pharmacokinetic parameters of harpagoside and cinnamic acid after oral administration of xuanshen extract (760 mg kg(-1)). After addition of syringin as internal standard, the analytes were isolated from plasma by liquid-liquid extraction. Separation was achieved on a Kromasil C18 column, and detection was by UV absorption at 272 nm. The described assay was validated in terms of linearity, accuracy, precision, recovery, and limit of quantification according to the FDA validation guidelines. Calibration curves for both analytes were linear with the coefficient of variation (r) for both was greater than 0.999. Accuracy for harpagoside and cinnamic acid ranged from 100.7-103.5% and 96.9-102.9%, respectively, and precision for both analytes were less than 8.5%. The main pharmacokinetic parameters found for harpagoside and cinnamic acid after oral infusion of xuanshen extract were as follows: Cmax 1488.7 +/- 205.9 and 556.8 +/- 94.2 ng mL(-1), Tmax 2.09 +/- 0.31 and (1.48 +/- 0.14 h, AUC(0-24) 10,336.4 +/- 1426.8 and 3653.1 +/- 456.4 ng h mL(-1), AUC(0-infinity) 11,276.8 +/- 1321.4 and 3704.5 +/- 398.8 ng h mL(-1), and t(1/2) 4.9 +/- 1.3 and 2.5 +/- 0.9 h, respectively. These results indicated that the proposed method is simple, selective, and feasible for pharmacokinetic study of radix Scrophulariae extract in rats.

  12. Emtricitabine seminal plasma and blood plasma population pharmacokinetics in HIV-infected men in the EVARIST ANRS-EP 49 study.

    Science.gov (United States)

    Valade, Elodie; Tréluyer, Jean-Marc; Illamola, Silvia M; Bouazza, Naïm; Foissac, Frantz; De Sousa Mendes, Maïlys; Lui, Gabrielle; Chenevier-Gobeaux, Camille; Suzan-Monti, Marie; Rouzioux, Christine; Assoumou, Lambert; Viard, Jean-Paul; Hirt, Déborah; Urien, Saïk; Ghosn, Jade

    2015-11-01

    We aimed to describe blood plasma (BP) and seminal plasma (SP) pharmacokinetics of emtricitabine (FTC) in HIV-1-infected men, assess its penetration in the male genital tract, and evaluate its impact on seminal plasma HIV load (spVL) detection. Men from the EVARIST ANRS EP49 study receiving combined antiretroviral therapy with FTC and with suppressed BP viral load were included in the study. A total of 236 and 209 FTC BP and SP concentrations, respectively, were available. A population pharmacokinetic model was developed with Monolix 4.1.4. The impact of FTC seminal exposure on spVL detection was explored by receiver operating characteristic (ROC) curves and mixed-effects logistic regressions. FTC BP pharmacokinetics was described by a two-compartment model. The addition of an effect compartment with different input and output constants best described FTC SP pharmacokinetics. No covariates were found to explain the variability in SP. FTC exposures (area under the concentration-time curve from 0 to 24 h [AUC0-24]) were higher in SP than in BP (median AUC0-24, 38.04 and 12.95 mg · liter(-1) · h, respectively). The median (range) SP-to-BP AUC0-24 ratio was 2.91 (0.84 to 10.08). Less than 1% of FTC AUC0-24 ratios were lower than 1. The impact of FTC SP AUC0-24 or FTC SP-to-BP AUC0-24 ratio on spVL detection was not significant (P = 0.943 or 0.893, respectively). This is the first population model describing FTC pharmacokinetics simultaneously in both BP and SP. FTC distributes well in the male genital tract with higher FTC concentrations in SP than in BP. FTC seminal plasma exposures were considered efficient in the majority of men.

  13. Determination and pharmacokinetic studies of arecoline in dog plasma by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Li, Bing; Zhou, Xu-Zheng; Li, Jian-Yong; Yang, Ya-Jun; Niu, Jian-Rong; Wei, Xiao-Juan; Liu, Xi-Wang; Li, Jin-Shan; Zhang, Ji-Yu

    2014-10-15

    A rapid and sensitive high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of arecoline concentration in dog plasma. Plasma sample was prepared by protein precipitation using n-hexane (containing 1% isoamyl alcohol) with β-pinene as an internal standard. Chromatographic separation was achieved on an Agilent C18 column (4.6×75mm, 3.5μm) using methanol: 5mM ammonium acetate as the mobile phase with isocratic elution. Mass detection was carried out using positive electrospray ionization in multiple reaction monitoring mode. The calibration curve for arecoline was linear over a concentration range of 2-500ng/mL. The intra-day and inter-day accuracy and precision were within the acceptable limits of ±10% at all concentrations. In summary, the LC-MS/MS method described herein was fully validated and successfully applied to the pharmacokinetic study of arecoline hydrobromide tablets in dogs after oral administration. Copyright © 2014. Published by Elsevier B.V.

  14. Transplacental pharmacokinetics and maternal/fetal plasma concentrations of cocaine in pregnant macaques near term.

    Science.gov (United States)

    Binienda, Z; Bailey, J R; Duhart, H M; Slikker, W; Paule, M G

    1993-01-01

    The transplacental pharmacokinetics of cocaine were studied in three pregnant rhesus monkeys (Macaca mulatta) at 150-154 days of pregnancy (term approximately 165 days). Animals were dosed intramuscularly with cocaine hydrochloride at 1 mg/kg, supplemented with a tritiated cocaine tracer. Plasma cocaine and its metabolite benzoylecgonine levels were determined after separation by HPLC and subsequent quantification by liquid scintillation spectrometry. Cocaine levels peaked in maternal blood within 10-20 min after dosing, and cocaine was detected in fetal blood within 5 min, reaching peak concentrations within 30-120 min. Mean maternal elimination half-lives (t1/2) for cocaine and benzoylecgonine were 1.2 +/- 0.5 hr and 12.4 +/- 6.6 hr (+/- SEM), respectively; fetal half-lives were 0.5 +/- 0.2 and 7.7 +/- 3.0 hr. Mean maternal residence times were 1.9 +/- 0.5 and 17.0 +/- 9.1 hr for cocaine and benzoylecgonine, respectively; fetal values were 2.1 +/- 0.2 and 11.6 +/- 3.5 hr. Total areas under the concentration versus time curves (AUCs) for cocaine and benzoylecgonine in maternal plasma were 360 +/- 38 and 585 +/- 260 (ng/ml) hr, respectively; fetal values were 104 +/- 29 and 262 +/- 61 (ng/ml) hr. Based on AUC comparisons for cocaine, fetal exposures are thus approximately one-third of maternal exposures, demonstrating that substantial exposure to cocaine does occur in utero.

  15. Nanoparticle Drug Loading as a Design Parameter to Improve Docetaxel Pharmacokinetics and Efficacy

    OpenAIRE

    Chu, Kevin S.; Schorzman, Allison N.; Finniss, Mathew C.; Bowerman, Charles J.; Peng, Lei; Luft, J. Christopher; Madden, Andrew; Wang, Andrew Z.; Zamboni, William C.; DeSimone, Joseph M.

    2013-01-01

    Nanoparticle (NP) drug loading is one of the key defining characteristics of a NP formulation. However, the effect of NP drug loading on therapeutic efficacy and pharmacokinetics has not been thoroughly evaluated. Herein, we characterized the efficacy, toxicity and pharmacokinetic properties of NP docetaxel formulations that have differential drug loading but are otherwise identical. Particle Replication in Non-wetting Templates (PRINT®), a soft-lithography fabrication technique, was used to ...

  16. A sensitive and robust HPLC assay with fluorescence detection for the quantification of pomalidomide in human plasma for pharmacokinetic analyses.

    Science.gov (United States)

    Shahbazi, Shandiz; Peer, Cody J; Polizzotto, Mark N; Uldrick, Thomas S; Roth, Jeffrey; Wyvill, Kathleen M; Aleman, Karen; Zeldis, Jerome B; Yarchoan, Robert; Figg, William D

    2014-04-01

    Pomalidomide is a second generation IMiD (immunomodulatory agent) that has recently been granted approval by the Food and Drug Administration for treatment of relapsed multiple myeloma after prior treatment with two antimyeloma agents, including lenalidomide and bortezomib. A simple and robust HPLC assay with fluorescence detection for pomalidomide over the range of 1-500ng/mL has been developed for application to pharmacokinetic studies in ongoing clinical trials in various other malignancies. A liquid-liquid extraction from human plasma alone or pre-stabilized with 0.1% HCl was performed, using propyl paraben as the internal standard. From plasma either pre-stabilized with 0.1% HCl or not, the assay was shown to be selective, sensitive, accurate, precise, and have minimal matrix effects (HPLC-FL assay allows a broader range of laboratories to measure pomalidomide for application to clinical pharmacokinetics.

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

    Science.gov (United States)

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

    2009-06-01

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

  18. Pharmacokinetics of oral ranitidine in Mexicans.

    Science.gov (United States)

    Castañeda-Hernández, G; Flores-Murrieta, F J; Granados-Soto, V; Herrera-Abarca, A; Pérez-Urizar, J; Herrera, J E; Hong, E

    1996-01-01

    The pharmacokinetics of oral ranitidine were studied in 24 Mexican male healthy volunteers. Subjects received a tablet containing 150 mg of ranitidine (Azantac, Glaxo de México, Mexico City) after an overnight fast and blood samples were drawn at several times for a period of 24 h. Ranitidine concentration in plasma was measured by high performance liquid chromatography and pharmacokinetic parameters were determined by non-compartmental analysis. Ranitidine plasma concentration increased with time, reaching a maximum of (mean +/- SEM) 484 +/- 34 ng/ml in 2.7 +/- 0.2 h. Plasma levels then decayed with a terminal half-life of 4.8 +/- 0.3 h. The area under the plasma concentration against time curve was 2440 +/- 126 ngh/ml. Oral ranitidine pharmacokinetic parameters in Mexicans appeared to be similar to those previously reported for Caucasians.

  19. [Determination of plasma concentration of quercetin, kaempferid and isorhamnetin in Hippophae rhamnoides extract by HPLC-MS/MS and pharmacokinetics in rats].

    Science.gov (United States)

    Liu, Yu; Yang, Juan; Tuo, Yang-ling; Wei, Ting; Zeng, Yong; Wang, Ping; Meng, Xian-li

    2015-10-01

    To establish an HPLC-MS/MS method for the analysis of quercetin, kaempferid and isorhamnetin in rats plasma and study its pharmamacokinetics after an intragastrical administration of Hippophae rhamnoides extracts. Five healthy male Sprague-Dawley (SD) rats were given single doses of H. rhamnoides extracts (quercetin 26.35 mg x kg(-1), kaempferid 4.040 mg x kg(-1), isorhamnetin 31.37 mg x kg(-1)), and then their orbital sinus blood samples were collected at different time points. The drug plasma concentration of the three flavonoids was determined by HPLC-MS/MS method. After that, the main pharmacokinetics parameters were calculated by using Kinetica 5. 0. 11 software. The methodological test showed that the linear concentration ranges of quercetin, kaempferid and isorhamnetin were 7.500-600.0 μg x L(-1) (R2 = 0.998 5), 1.000-80.00 μg x L(-1) (R2 = 0.998 5 ) and 10.00-800.0 μg x L(-1) (R2 = 0.998 0), respectively. The inner and inter-days precisions were both less than 14.0%. The plasma samples showed a good stability and consistency with the requirement of biological sample analysis after the samples were frozen once and placed at - 20 degrees C for 15 d and room temperature for 6 h and the treated analytes were placed at -20 degrees C for 24 h. For quercetin, the pharmacokinetic parameter t(½β), AUC(0-∞), MRT(0.∞), C.(max) and T(max) were (113.3 ± 19.37) min, (12 542.14 ± 3 504.05) μg x h x L(-1), (119.6 ± 13.29) h, (164.6 ± 27.33) μg x L(-1) and (5.199 ± 0.840 3) h, respectively. For kaempferid, the pharmacokinetic parameters t(½β), AUC(0-t), MRT(0-∞), C(max) and T(max) were (79.85 ± 17.15) min, (934.51 ± 94.59) μg x h x L(-1), (81.50 ± 13.75) h, (80.15 ± 14.24) μg x L(-1) and (3.827 ± 0.902 7) h, respectively. For isorhamnetin, the pharmacokinetic parameters t1,2,, AUC(0-t), MRT(0-∞), C(max) and T(max) were (118.3 ± 20.73) min, (26 067.77 ± 4 124.60) μg x h x L(-1), (129.0 ± 16.30) h, (269.6 ± 29.32) μg x L(-1) and (6.513 ± 1

  20. Pharmacokinetics of tildipirosin in bovine plasma, lung tissue, and bronchial fluid (from live, nonanesthetized cattle).

    Science.gov (United States)

    Menge, M; Rose, M; Bohland, C; Zschiesche, E; Kilp, S; Metz, W; Allan, M; Röpke, R; Nürnberger, M

    2012-12-01

    The pharmacokinetics of tildipirosin (Zuprevo(®) 180 mg/mL solution for injection for cattle), a novel 16-membered macrolide for treatment, control, and prevention of bovine respiratory disease, were investigated in studies collecting blood plasma, lung tissue, and in vivo samples of bronchial fluid (BF) from cattle. After single subcutaneous (s.c.) injection at 4 mg/kg body weight, maximum plasma concentration (C(max)) was 0.7 μg/mL. T(max) was 23 min. Mean residence time from the time of dosing to the time of last measurable concentration (MRT(last)) and terminal half-life (T(1/2) ) was 6 and 9 days, respectively. A strong dose-response relationship with no significant sex effect was shown for both C(max) and area under the plasma concentration-time curve from time 0 to the last sampling time with a quantifiable drug concentration (AUC(last) ) over the range of doses up to 6 mg/kg. Absolute bioavailability was 78.9%. The volume of distribution based on the terminal phase (V(z)) was 49.4 L/kg, and the plasma clearance was 144 mL/h/kg. The time-concentration profile of tildipirosin in BF and lung far exceeded those in blood plasma. In lung, tildipirosin concentrations reached 9.2 μg/g at 4 h, peaked at 14.8 μg/g at day 1, and slowly declined to 2.0 μg/g at day 28. In BF, the concentration of tildipirosin reached 1.5 and 3.0 μg/g at 4 and 10 h, maintained a plateau of about 3.5 μg/g between day 1 and 3, and slowly declined to 1.0 at day 21. T(1/2) in lung and BF was approximately 10 and 11 days. Tildipirosin is rapidly and extensively distributed to the respiratory tract followed by slow elimination.

  1. Determination of levamisole, aminorex, and pemoline in plasma by means of liquid chromatography-mass spectrometry and application to a pharmacokinetic study of levamisole.

    Science.gov (United States)

    Hess, Cornelius; Ritke, Natalie; Sydow, Konrad; Mehling, Lena-Maria; Ruehs, Hauke; Madea, Burkhard; Musshoff, Frank

    2014-10-01

    Levamisole is an anti-helminthic drug and gained forensic interest after it was found that it was used as a cocaine adulterant. A liquid chromatography-mass spectrometry (LC-MS) method for the determination of levamisole and its metabolite aminorex in human plasma is described. Selectivity is given; calibration curves were linear within a calibration range of 1 ng/mL-500 ng/mL. Limits of detection and quantification (LODs, LOQs) were 0.85 ng/mL for levamisole and 0.09 ng/mL, and 0.34 ng/mL for aminorex, respectively. Precision data was in accordance with the GTFCh guidelines. The validated method was successfully applied to study the pharmacokinetics of levamisole after administration of 100 mg of levamisole orally. Levamisole could be detected up to 36 h after ingestion in serum, while aminorex never exceeded the LOQ. A one-compartment model best described levamisole pharmacokinetics. The following parameters were calculated: ka = 1.2 [1/h], CL/F = 52 l/h, V/F = 347 l, f (renal) = 0.0005, t ½ = 2.0 h, AUC = 1923 ng/mL*h, cmax = 214 ng/mL, tmax = 1.98 h. Levamisole could be quantified in 42.5% of cocaine--positive plasma samples (2.2 to 224 ng/mL). Aminorex was positive in only 11.3% of the cases; however, it was never found higher than the LOQ. Pemoline, another stimulant detected in horse urine samples after administration of levamisole, was not found either in serum or in urine of this pharmacokinetic study. In post-mortem cases, levamisole and aminorex could be detected in femoral blood and the urine of cocaine users. Pemoline was not detected.

  2. Plasma and interstitial fluid pharmacokinetics of enrofloxacin, its metabolite ciprofloxacin, and marbofloxacin after oral administration and a constant rate intravenous infusion in dogs.

    Science.gov (United States)

    Bidgood, T L; Papich, M G

    2005-08-01

    Enrofloxacin and marbofloxacin were administered to six healthy dogs in separate crossover experiments as a single oral dose (5 mg/kg) and as a constant rate IV infusion (1.24 and 0.12 mg/h.kg, respectively) following a loading dose (4.47 and 2 mg/kg, respectively) to achieve a steady-state concentration of approximately 1 microg/mL for 8 h. Interstitial fluid (ISF) was collected with an in vivo ultrafiltration device at the same time period as plasma to measure protein unbound drug concentrations at the tissue site and assess the dynamics of drug distribution. Plasma and ISF were analyzed for enrofloxacin, its active metabolite ciprofloxacin, and for marbofloxacin by high performance liquid chromatography (HPLC). Lipophilicity and protein binding of enrofloxacin were higher than for marbofloxacin and ciprofloxacin. Compared to enrofloxacin, marbofloxacin had a longer half-life, higher Cmax, and larger AUC(0-infinity) in plasma and ISF after oral administration. Establishing steady state allowed an assessment of the dynamics of drug concentrations between plasma and ISF. The ISF and plasma-unbound concentrations were similar during the steady-state period despite differences in lipophilicity and pharmacokinetic parameters of the drugs.

  3. Pharmacokinetics of rilmenidine

    Energy Technology Data Exchange (ETDEWEB)

    Genissel, P.; Bromet, N. (Biopharmacie Servier, Orleans (France))

    1989-09-18

    Rilmenidine is a novel antihypertensive agent related to alpha 2-adrenoceptor agonist, used in the treatment of mild or moderate hypertension at the oral dose of 1 mg once a day or 1 mg twice a day. The pharmacokinetic parameters were investigated after single or repeated administration in healthy subjects, using labeled and unlabeled compounds. Rilmenidine was rapidly and extensively absorbed, with an absolute bioavailability close to one and a time to peak plasma concentration of two hours. Rilmenidine was not subjected to presystemic metabolism. Distribution was independent of the free fraction since rilmenidine was weakly bound to plasma proteins (less than 10 percent). The volume of distribution was approximately 5 liters/kg (315 liters). Elimination was rapid, with a total body plasma clearance of approximately 450 ml/minute and an elimination half-life of approximately eight hours. Renal excretion was the major elimination process (two thirds of the total clearance); the parent drug in urine accounted for about 65 percent of the dose administered. Metabolism was very poor; few metabolites were found in urine and no metabolites were detected in plasma. Linear pharmacokinetics was demonstrated for rilmenidine from 0.5 to 2 mg; at 3 mg, a slight deviation from linearity was observed. In repeated administration, the linearity with dose of the pharmacokinetics of rilmenidine was confirmed.

  4. Determination of Captopril in Human Plasma by High—Performance Liquid Chromatography and Study on the Pharmacokinetics after a Single Oral Dose

    Institute of Scientific and Technical Information of China (English)

    YANGLi; XUAi-xia; ZHAORong-sheng; YANBao-xia

    2003-01-01

    Aim:To establish a simple high-performance liquid chromatography method for the determination of captopril in human plasma and study the phamacokinetics of captopril in healthy volunteers.Methods:Captopril was stabilized by forming an adduct with p-bromophenacyl bromide and this adduct in plasma was measured by high-performance liquid chromatography with UV detection following a single oral dose 50mg of captopril test and reference preparations respectively given to 18 healthy volunteers.Results:The standard curve was liner over a range of 25-1200ng·mL-1.The quantitative limit of detection was 25ng·mL-1.The RSD of inter-and intra-assay were below 8%.On the basis of elaborated method,single-dose pharmacokinetics in 18 healthy volunteers have been investigated.The comparison of the pharmacokinetic parameters was performed.The pharmacokinetic parameters of test and reference tablets were calculated as follows:tmax were (0.64±0.18)h and (0.82±0.41)h;Cmax were (600.2±194.3)ng·mL-1 and (582.7±175.3)ng·mL-1.AUC0→gh were (1448.5±483.7)ng·h·mL-1 and (1389.9±392.5)ng·h·mL-1;AUC0→∞ were (1869.4±701.6)ng·h·mL-1 and (1781±615.5)ng·h·mL-1and (1389.9±392.5)ng·h·mL-1;AUC0→∞were (1869.4±701.6)ng·h·mL-1 and (1781.8±615.5)ng·h·mL-1,respectively.Conclusion:The improved analytical method for captopril was found to be sensitive,simple and rapid,suitable for application in pharmacokinetic studies and routine determination of numerous samples.

  5. Novel LC- ESI-MS/MS method for desvenlafaxine estimation human plasma: application to pharmacokinetic study.

    Science.gov (United States)

    Kancharla, Pushpa Kumari; Kondru, Venu Gopal Raju; Dannana, Gowri Sankar

    2016-02-01

    A simple, sensitive and specific liquid chromatography tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the quantification of desvenlafaxine in human plasma using desvenlafaxine d6 as an internal standard (IS). Chromatographic separation was performed using a Thermo-BDS hypersil C8 column (50 × 4.6 mm, 3 µm) with an isocratic mobile phase composed of 5 mM ammonium acetate buffer: methanol (20:80, v/v), at a flow rate of 0.80 mL/min. Desvenlafaxine and desvenlafaxine d6 were detected with proton adducts at m/z 264.2/58.1 and 270.2/ 64.1 in multiple reaction monitoring positive mode, respectively. Liquid-liquid extraction was used to extract the drug and the IS. The method was linear over the concentration range 1.001-400.352 ng/mL with a correlation coefficient of ≥0.9994. This method demonstrated intra and inter-day precision within 0.7-5.5 and 1.9-6.8%, and accuracy within 95.3-107.4 and 93.4-99.5%. Desvenlafaxine was found to be stable throughout the freeze-thaw cycles, bench-top and long-term matrix stability studies. The developed and validated method can be successfully applied for the bioequivalence/pharmacokinetic studies of desvenlafaxine in pharmaceutical dosage forms. Copyright © 2015 John Wiley & Sons, Ltd.

  6. Determination of piracetam in rat plasma by LC-MS/MS and its application to pharmacokinetics.

    Science.gov (United States)

    Wang, Xianqin; Zhu, Jiayin; Xu, Renai; Yang, Xuezhi; Wu, Haiya; Lin, Dan; Ye, Faqing; Hu, Lufeng

    2010-10-01

    A sensitive and selective liquid chromatography-tandem mass spectrometry method for the determination of piracetam in rat plasma was developed and validated over the concentration range of 0.1-20 µg/mL. After addition of oxiracetam as internal standard, a simplified protein precipitation with trichloroacetic acid (5%) was employed for the sample preparation. Chromatographic separation was performed by a Zorbax SB-Aq column (150 × 2.1 mm, 3.5 µm). The mobile phase was acetonitrile-1% formic acid in water (10:90 v/v) delivered at a flow rate of 0.3 mL/min. The MS data acquisition was accomplished in multiple reaction monitoring mode with a positive electrospray ionization interface. The lower limit of quantification was 0.1 µg/mL. For inter-day and intra-day tests, the precision (RSD) for the entire validation was less than 9%, and the accuracy was within the 94.6-103.2% range. The developed method was successfully applied to pharmacokinetic studies of piracetam in rats following single oral administration dose of 50 mg/kg. Copyright © 2010 John Wiley & Sons, Ltd.

  7. Fluorescence detection of Zabofloxacin, a novel fluoroquinolone antibiotic, in plasma, bile, and urine by HPLC: the first oral and intravenous applications in a pharmacokinetic study in rats.

    Science.gov (United States)

    Jin, Hyo Eon; Kang, In Hyul; Shim, Chang Koo

    2011-01-01

    To develop an HPLC method using fluorescence detection for the pharmacokinetic evaluation of levels of zabofloxacin, a novel broad spectrum fluoroquinolone antibiotic, in the plasma, bile and urine of rats. A simple reversed-phase HPLC method using a C18 column with fluorescence detection was developed and validated for the simultaneous determination of zabofloxain and enrofloxacin as an internal standard. The plasma sample was treated with methanol for protein precipitation, and treatment of the bile and urine samples included deproteinization and extraction using chloroform. The applicability of the developed assay method to pharmacokinetic studies of zabofloxacin in rats was examined. Zabofloxacin was intravenously and orally administered to rats at a dose of 20 mg/kg. The limits of quantification (LOQ) was determined to be 50 ng/mL for the plasma with acceptable linearity ranging from 50 to 25,000 ng/mL (R>0.999), and 0.5 μg/mL for the bile and urine samples with acceptable linearity ranging from 0.5 to 100 μg/mL (R>0.999). The validation parameters for zabofloxacin were found to be acceptable according to FDA assay validation (2001). While zabofloxacin in plasma and urine has been stable in all tested handling conditions, it has been unstable in bile during freeze-thaw cycles for 24 h at room temperature. Following intravenous and oral administration of zabofloxacin to rats at a dose of 20 mg/kg, concentration was quantifiable in plasma for up to 8 h. The bioavailability of zabofloxacin was 27.7%, and it was excreted into bile and urine at about 8% each per oral administration. These observations suggest that a validated assay can be used in pharmacokinetic studies of zabofloxacin in small animals. Due to the limited stability of zabofloxcin in rat bile, freeze-thaw cycles or prolonged handling at room temperature is not recommended. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on

  8. Quantitation of Metformin in Human Plasma and Urine by Hydrophilic Interaction Liquid Chromatography and Application to a Pharmacokinetic Study

    DEFF Research Database (Denmark)

    Nielsen, Flemming; Hougaard Christensen, Mette Marie; Brøsen, Kim

    2014-01-01

    : We describe an analytical method for the quantification of the widely used antihyperglycemic agent, metformin, in human plasma and urine. The separation was performed using isocratic hydrophilic interaction liquid chromatography on a Luna hydrophilic interaction liquid chromatography column (125.......5% in plasma and 1.6% to 6.2% in urine. Between-day reproducibility ranged from 2.9% to 5.3% in plasma and 0.6% to 1.8% in urine. The inaccuracy expressed as bias ranged from -3.1% to 1.9% in plasma and from -7.2% to 0.7% in urine. The lower limit of quantification for metformin in plasma was 5 ng....../mL and in urine was 40 ng/mL. The method was therefore considered to be precise, accurate, reproducible, and sensitive enough to be appropriate for pharmacokinetic studies of metformin. The applicability of the method for human pharmacokinetic studies was demonstrated by dosing a healthy male volunteer with 500...

  9. On the accuracy of estimation of basic pharmacokinetic parameters by the traditional noncompartmental equations and the prediction of the steady-state volume of distribution in obese patients based upon data derived from normal subjects.

    Science.gov (United States)

    Berezhkovskiy, Leonid M

    2011-06-01

    The steady-state and terminal volumes of distribution, as well as the mean residence time of drug in the body (V(ss), V(β), and MRT) are the common pharmacokinetic parameters calculated using the drug plasma concentration-time profile C(p) (t) following intravenous (i.v. bolus or constant rate infusion) drug administration. These calculations are valid for the linear pharmacokinetic system with central elimination (i.e., elimination rate being proportional to drug concentration in plasma). Formally, the assumption of central elimination is not normally met because the rate of drug elimination is proportional to the unbound drug concentration at elimination site, although equilibration between systemic circulation and the site of clearance for majority of small molecule drugs is fast. Thus, the assumption of central elimination is practically quite adequate. It appears reasonable to estimate the extent of possible errors in determination of these pharmacokinetic parameters due to the absence of central elimination. The comparison of V(ss), V(β), and MRT calculated by exact equations and the commonly used ones was made considering a simplified physiologically based pharmacokinetic model. It was found that if the drug plasma concentration profile is detected accurately, determination of drug distribution volumes and MRT using the traditional noncompartmental calculations of these parameters from C(p) (t) yields the values very close to that obtained from exact equations. Though in practice, the accurate measurement of C(p) (t), especially its terminal phase, may not always be possible. This is particularly applicable for obtaining the distribution volumes of lipophilic compounds in obese subjects, when the possibility of late terminal phase at low drug concentration is quite likely, specifically for compounds with high clearance. An accurate determination of V(ss) is much needed in clinical practice because it is critical for the proper selection of drug treatment

  10. Plasma Pharmacokinetics of Polyphenols in a Traditional Japanese Medicine, Jumihaidokuto, Which Suppresses Propionibacterium acnes-Induced Dermatitis in Rats.

    Science.gov (United States)

    Matsumoto, Takashi; Matsubara, Yousuke; Mizuhara, Yasuharu; Sekiguchi, Kyoji; Koseki, Junichi; Tsuchiya, Kazuaki; Nishimura, Hiroaki; Watanabe, Junko; Kaneko, Atsushi; Maemura, Kazuya; Hattori, Tomohisa; Kase, Yoshio

    2015-09-30

    Most orally administered polyphenols are metabolized, with very little absorbed as aglycones and/or unchanged forms. Metabolic and pharmacokinetic studies are therefore necessary to understand the pharmacological mechanisms of polyphenols. Jumihaidokuto (JHT), a traditional Japanese medicine, has been used for treatment of skin diseases including inflammatory acne. Because JHT contains various types of bioactive polyphenols, our aim was to clarify the metabolism and pharmacokinetics of the polyphenols in JHT and identify active metabolites contributing to its antidermatitis effects. Orally administered JHT inhibited the increase in ear thickness in rats induced by intradermal injection of Propionibacterium acnes. Quantification by LC-MS/MS indicated that JHT contains various types of flavonoids and is also rich in hydrolysable tannins, such as 1,2,3,4,6-penta-O-galloyl glucose. Pharmacokinetic and antioxidant analyses showed that some flavonoid conjugates, such as genistein 7-O-glucuronide and liquiritigenin 7-O-glucuronide, appeared in rat plasma and had an activity to inhibit hydrogen peroxide-dependent oxidation. Furthermore, 4-O-methylgallic acid, a metabolite of Gallic acid, appeared in rat plasma and inhibited the nitric oxide reaction. JHT has numerous polyphenols; it inhibited dermatitis probably via the antioxidant effect of its metabolites. Our study is beneficial for understanding in vivo actions of orally administered polyphenol drugs.

  11. Plasma Pharmacokinetics of Polyphenols in a Traditional Japanese Medicine, Jumihaidokuto, Which Suppresses Propionibacterium acnes-Induced Dermatitis in Rats

    Directory of Open Access Journals (Sweden)

    Takashi Matsumoto

    2015-09-01

    Full Text Available Most orally administered polyphenols are metabolized, with very little absorbed as aglycones and/or unchanged forms. Metabolic and pharmacokinetic studies are therefore necessary to understand the pharmacological mechanisms of polyphenols. Jumihaidokuto (JHT, a traditional Japanese medicine, has been used for treatment of skin diseases including inflammatory acne. Because JHT contains various types of bioactive polyphenols, our aim was to clarify the metabolism and pharmacokinetics of the polyphenols in JHT and identify active metabolites contributing to its antidermatitis effects. Orally administered JHT inhibited the increase in ear thickness in rats induced by intradermal injection of Propionibacterium acnes. Quantification by LC-MS/MS indicated that JHT contains various types of flavonoids and is also rich in hydrolysable tannins, such as 1,2,3,4,6-penta-O-galloyl glucose. Pharmacokinetic and antioxidant analyses showed that some flavonoid conjugates, such as genistein 7-O-glucuronide and liquiritigenin 7-O-glucuronide, appeared in rat plasma and had an activity to inhibit hydrogen peroxide-dependent oxidation. Furthermore, 4-O-methylgallic acid, a metabolite of Gallic acid, appeared in rat plasma and inhibited the nitric oxide reaction. JHT has numerous polyphenols; it inhibited dermatitis probably via the antioxidant effect of its metabolites. Our study is beneficial for understanding in vivo actions of orally administered polyphenol drugs.

  12. Pharmacokinetics of dilevalol and its conjugates in man. Assay method for plasma, blood, urine and bile samples and preliminary pharmacokinetic studies.

    Science.gov (United States)

    Neubeck, M; Becker, C; Henke, D; Rösch, W; Spahn-Langguth, H; Mutschler, E

    1993-09-01

    The renal and biliary excretion of the beta-adrenoceptor blocking agent dilevalol (CAS 75659-07-3) and its conjugates was examined in a preliminary pharmacokinetic study. Plasma, urine and bile dilevalol concentrations were determined with a simplified procedure that is based on alkaline liquid-liquid extraction using diethyl ether and subsequent reversed-phase HPLC separation of the reconstituted samples (on a PRP-1 stationary phase using a mixture of methanol and pH 9.8 carbonate buffer as mobile phase). Triamterene was used as internal standard. The quantification of the conjugates was accomplished indirectly via enzymatic hydrolysis (glusulase) with and without addition of the beta-glucuronidase inhibitor 1,4-saccharolactone (at a final concentration of 5.5 mmol/l). In the pharmacokinetic study healthy volunteers and cholecystectomised patients with a T-drain received a single oral dose of 200 mg dilevalol. Furthermore, to healthy volunteers an i.v. dose of 60 mg dilevalol was given in order to estimate the absolute bioavailability. From the obtained data the systemic plasma clearance was calculated to be 1708 ml/min. The oral bioavailability was calculated to be 16%. The log concentration-time curves of the metabolites paralleled those of dilevalol in the terminal section with average terminal half-lives of approx. 5 h. In volunteers the fractions of the dose excreted renally were 0.5% for parent drug, 23% for the glucuronide(s) and 8% for the sulfate. The corresponding values found for the patients were not significantly different. In the patients' bile only 1.2% of the total dose were found (0.03% dilevalol, 1.1% dilevalol glucuronide(s), 0.1% dilevalol sulfate).(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Pharmacokinetics of cefpodoxime proxetil with special reference to biochemical parameters, tissue residue, and spermatozoa motility in rats

    Directory of Open Access Journals (Sweden)

    Momin A Mujeeb

    2011-01-01

    Full Text Available Background : Cefpodoxime is a semisynthetic third generation cephalosporin analogue with a relatively broader spectrum of antimicrobial activity against gram negative and gram positive organisms. This is attributed to their somewhat increased resistance to degradation by the betalactamase. Cefpodoxime shows good activity against Klebsiella pneumonia, many members of enterobactericeae and almost all strains of Escherichia coli. It is extensively used in human beings against infections caused by susceptible organisms for a prolonged period and even without its judicious indication. Though various researchers have worked on the pharmacokinetic aspects of the drug, its effects on biochemical parameters and spermatozoa activity are scarcely available in literature. Aim : To determine the oral kinetic ( blood and tissue after single therapeutic dose of cefpodoxime proxetil (20mg/kg oral bid 7 days in rats of either sex on tissue half life and certain biochemical parameters such as glucose, hemoglobin, protein, ALT, AST and other parameters like tissue residue, sperm count and spermatozoa motility in male rats. Materials and Methods : For kinetic studies,24 Wister rats of either sex, 3 months of age, (180-210 gm were used.(Group I-IV; n=6 Blood samples collected from each animal of Group IV through heart puncture at 0 hour to serve as predrug control. All the group (I-IV received cefpodoxime proxetil 20 mg/kg once orally as a single dose. At the end of 1,4,12 and 24 hour post oral administration, GroupI,II,III and IVwere utilized for kinetic studies. Blood samples were collected from each animal and vital organs viz brain, lung, liver, spleen, kidney and heart were dissected out for drug analysis and determination of weight. For biochemical parameters, tissue residue and spermatozoa motility, twelve male rats were randomly divided into Groups A and B (n=6 Group B received cefpodoxime (20mg/kg orally bid 7 days while Group A served as control

  14. Preliminary buprenorphine sublingual tablet pharmacokinetic data in plasma, oral fluid and sweat during treatment of opioid-dependent pregnant women

    Science.gov (United States)

    Concheiro, Marta; Jones, Hendreé E.; Johnson, Rolley E.; Choo, Robin; Huestis, Marilyn A.

    2011-01-01

    Background Buprenorphine is currently under investigation as a pharmacotherapy to treat pregnant women for opioid dependence. This research evaluates buprenorphine (BUP), norbuprenophine (NBUP), buprenorphine-glucuronide (BUP-Gluc) and norbuprenorphine-glucuronide (NBUP-Gluc) pharmacokinetics after high dose (14–20 mg) BUP sublingual tablet administration in three opioid-dependent pregnant women. Methods Oral fluid and sweat specimens were collected in addition to plasma specimens for 24 h during gestation weeks 28 or 29 and 34, and 2 months after delivery. Tmax was not affected by pregnancy; however, BUP and NBUP Cmax and AUC0–24h tended to be lower during pregnancy compared to postpartum levels. Results Statistically significant but weak positive correlations were found for BUP plasma and OF concentrations, and BUP/NBUP ratios in plasma and OF. Conclusion Statistically significant negative correlations were observed for times of specimen collection and BUP and NBUP OF/plasma ratios. BUP-Gluc and NBUP-Gluc were detected in only 5% of OF specimens. In sweat, BUP and NBUP were detected in only 4 of 25 (12 or 24 h) specimens in low concentrations (<2.4 ng/patch). These preliminary data describe BUP and metabolite pharmacokinetics in pregnant women and suggest that, like methadone, upward dose adjustments may be needed with advancing gestation. PMID:21860340

  15. Determination of salbutamol in human plasma and urine using liquid chromatography coupled to tandem mass spectrometry and its pharmacokinetic study.

    Science.gov (United States)

    Zhang, Dujuan; Teng, Yanni; Chen, Keguang; Liu, Sha; Wei, Chunmin; Wang, Benjie; Yuan, Guiyan; Zhang, Rui; Liu, Xiaoyan; Guo, Ruichen

    2012-10-01

    A sensitive and selective liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was developed and validated for the determination of salbutamol in human plasma and urine, and successfully applied to the pharmacokinetic study of salbutamol in Chinese healthy volunteers after inhalation of salbutamol sulfate aerosol. Salbutamol and the internal standard (IS) acetaminophen in plasma and urine were extracted with ethyl acetate, separated on a C(18) reversed-phase column, eluted with mobile phase of acetonitrile-ammonium acetate (5 m m; 30:70, v/v), ionized by positive ion pneumatically assisted electrospray and detected in the multi-reaction monitoring mode using precursor → product ions of m/z 240.2 → 148.1 for salbutamol and 152 → 110 for the IS. The lower limits of quantitation of salbutamol in human plasma and urine by this method were 0.02 and 1 ng/mL, respectively. The specificity, matrix effect, recovery, sensitivity, linearity, accuracy, precision and several stabilities were validated for salbutamol in human plasma and urine. In conclusion, the validation results showed that this method is robust, specific and sensitive, and can successfully fulfill the requirement of clinical pharmacokinetic study of salbutamol in healthy Chinese volunteers.

  16. Effect of gasification parameter on coal gasification in thermal plasma

    Energy Technology Data Exchange (ETDEWEB)

    Shen, S.; Pang, X.; Bao, W.; Lo, Y.; Zhu, S. [Taiyuan University of Technology, Taiyuan (China)

    2004-12-01

    The influence of several parameters such as the power input of plasma jet, vapor and air input etc on gas composition and carbon conversion from coal gasification in an air-steam plasma jet was studied. The main gaseous products are H{sub 2}, CO, CO{sub 2}, CH{sub 2}4 and tar was discovered. Results show that the concentration of H{sub 2}, CO and carbon conversion increases, and the concentration of CO{sub 2} significantly decreases, when the power input of plasma jet is raised. The concentration of H{sub 2} increases when the vapor flux is increased, but excessive steam can decrease carbon conversion. The carbon conversion is enhanced by decreasing feed rate. The air flux should be reduced to improve the quality of coal gas in a certain range. The carbon conversion of Datong coal can exceed 95% at appropriate condition. 18 refs., 4 figs., 2 tabs.

  17. Programmable physical parameter optimization for particle plasma simulations

    Science.gov (United States)

    Ragan-Kelley, Benjamin; Verboncoeur, John; Lin, Ming-Chieh

    2012-10-01

    We have developed a scheme for interactive and programmable optimization of physical parameters for plasma simulations. The simulation code Object-Oriented Plasma Device 1-D (OOPD1) has been adapted to a Python interface, allowing sophisticated user or program interaction with simulations, and detailed numerical analysis via numpy. Because the analysis/diagnostic interface is the same as the input mechanism (the Python programming language), it is straightforward to optimize simulation parameters based on analysis of previous runs and automate the optimization process using a user-determined scheme and criteria. An example use case of the Child-Langmuir space charge limit in bipolar flow is demonstrated, where the beam current is iterated upon by measuring the relationship of the measured current and the injected current.

  18. Investigation of plasma parameters in an active screen cage-pulsed dc plasma used for plasma nitriding

    Science.gov (United States)

    Naeem, M.; Khattak, Z. I.; Zaka-ul-Islam, M.; Shabir, S.; Khan, A. W.; Zakaullah, M.

    2014-11-01

    Active screen cage-pulsed dc plasmas are widely used in the material processing applications such as plasma nitriding, carburizing and nitrocarburizing. Specifically for plasma nitriding applications, a H2-N2 mixture is used. In this article, a study of the electron number density (ne), atomic nitrogen density ([N]), electron temperature ? and the excitation temperature ? is reported in the presence of an active screen cage-pulsed dc plasma. The ne and ? are determined here by a triple Langmuir probe, while [N] and ? are estimated by optical emission spectroscopy (OES). The two temperatures and their ratio ? are compared for different input parameters (such as applied power, gas pressure and H2 percentage). This study is useful in active screen cage plasma nitriding applications where only few plasma diagnostic measurements have been reported.

  19. Pharmacokinetics and tissue distribution of novel platinum containing anticancer agent BP‐C1 studied in rabbits using sector field inductively coupled plasma mass spectrometry

    Science.gov (United States)

    Navolotskii, Denis V.; Ivanenko, Natalya B.; Fedoros, Elena I.; Panchenko, Andrey V.

    2015-01-01

    A method of platinum quantification in whole blood samples after microwave digestion using sector field inductively coupled plasma mass spectrometry has been developed. The following analytical figures of merit have been established: limit of detection 1.1 µg/L for blood samples, dynamic range 3.6–200 µg/L, intra‐day precision (relative standard deviation, n = 9) did not exceed 5%. Spiked samples were analyzed for method validation. The method was used for pharmacokinetics studies of a novel anti‐cancer drug BP‐С1, a complex of cis‐configured platinum and benzene‐poly‐carboxylic acids. Main pharmacokinetic parameters (area under curve, maximum concentration, clearance, half‐life times for α‐ and β‐phase) were estimated for two dosage forms of BP‐C1 0.05 and 0.125 mass %. Pharmacokinetic curves were assessed for single and course administration. Studies were performed using rabbits (n = 6) as a model. BP‐C1 was injected intramuscularly. The study established dose proportionality of the tested dosage forms and suggested clinical dosing schedule: 5 days of injections followed by 2 days’ break. Platinum tissue distribution was studied in tissue samples collected 20 days after the last injection. Predominant platinum accumulation was observed in kidneys, liver, and muscles near injection site. ‘Slow’ phase of platinum excretion kinetics may be related to the muscles at the injection site. © 2015 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd. PMID:26061351

  20. Study on Performance Parameters of the Plasma Source for a Short-Conduction-Time Plasma Opening Switch

    Institute of Scientific and Technical Information of China (English)

    LUO Weixi; ZENG Zhengzhong; WANG Liangping; LEI Tianshi; HU Yixiang; HUANG Tao; SUN Tieping

    2012-01-01

    Plasma source performance parameters, including plasma ejection density and velocity, greatly affect the operation of a short-conduction-time plasma opening switch (POS). In this paper, the plasma source used in the POS of Qiangguang I generator is chosen as the study object. At first the POS working process is analyzed. The result shows that the opening performance of the POS can be improved by increasing the plasma ejection velocity and decreasing the plasma density. The influence of the cable plasma gun structure and number on the plasma ejection parameters is experimentally investigated with two charge collectors. Finally a semi-empirical model is proposed to describe the experimental phenomenon.

  1. Effect of Substrate Potential on Plasma Parameters of Magnetic Multicusp Plasma Source

    Science.gov (United States)

    Ueda, Yoshio; Goto, Masahiro

    1998-06-01

    The effect of substrate potential on plasmas produced in a magnetic multicusp plasma source has been studied experimentally. Plasma parameters such as electron temperature and plasma potential are estimated from electron energy distribution function numerically calculated from probe current-voltage characteristics. For a substrate potential of -150 V with respect to the source chamber, which is much lower than substrate floating potentials, the plasma parameters are not affected by the application of the potential. However, for the case where the substrate is shorted with the source chamber, the high energy component of electrons significantly decreases in comparison with the floating case leading to the reduction of electron temperature. In this case, plasma potential is positive with respect to the substrate to suppress electron loss but its absolute value is only of the order of electron temperature in eV, which is much lower than the potential between the plasma and the substrate in the floating case. This discharge mode could be advantageous in significantly reducing the ion impact energy to the substrate plate.

  2. Pharmacokinetic parameters and killing rates in serum of volunteers receiving amoxicillin, cefadroxil or cefixime alone or associated with niflumic acid or paracetamol.

    Science.gov (United States)

    Carsenti-Etesse, H; Farinotti, R; Durant, J; Roger, P M; De Salvador, F; Bernard, E; Rouveix, B; Dellamonica, P

    1998-01-01

    Pharmacokinetic parameters and killing rates in serum of volunteers receiving amoxicillin, cefadroxil or cefixime alone or associated with niflumic acid or paracetamol were studied. Niflumic acid (250 mg) or analgesic and antipyretic drugs such as paracetamol (500 mg) are often combined with antibiotics to avoid inflammation and pain in acute ear, nose and throat diseases. Pharmacokinetic interactions between these two classes of drugs have been described in experimental models, and exceptionally in humans. The aim of the present investigation was to study the interactions of these two drugs with three antibiotics (amoxicillin 500 mg x 2, cefadroxil 500 mg x 2, cefixime 200 mg and one placebo capsule) on pharmacodynamic parameters and on rate of killing in the serum of six healthy volunteers receiving the antibiotic associated or not with the product in a randomized cross-over double-blind trial. The bacteria most often involved in sinusitis, bronchitis and otitis media (Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus) three target diseases for oral cephalosporins and amoxicillin, were chosen for bacteriological study. Blood samples were obtained at 0.25, 0.50, 1, 1.5, 2, 4, 6 and 12 h after oral administration of antibiotics alone or associated with the drugs. There was a wash-out period of at least 1 week between the eleven sequences. Antibiotics were measured by two methods: bioassay and high performance liquid chromatography (HPLC). All serum samples obtained at peak level, 4 and 6 h were tested for killing rate. Area under the time kill curve was calculated by the trapezoidal rule method and relative bioactivity in percent was defined as follows: (AUC control - AUC test)/AUC control x 100. No pharmacokinetic interaction was found in the AUC and T1/2 of the plasma concentrations of the antibiotics or associated with the drugs, regardless of dose, as determined by HPLC or microbiological assay. For these beta-lactam antibiotics killing

  3. Pharmacokinetic analysis of adriamycin (doxorubicin and related fluorescent compounds in Ehrlich tumor-bearing mouse plasma and tissues.

    Directory of Open Access Journals (Sweden)

    Shinozawa,Shinya

    1982-04-01

    Full Text Available Pharmacokinetic analysis of the distribution and concentration of adriamycin (ADM in mouse plasma and tissues was carried out by differentiating the unmetabolized form from metabolized ones using high-performance liquid chromatography after a single intravenous injection. Marked differences between ADM and total ADM equivalent values (total ADM values or its metabolized forms were observed in the pharmacokinetic behavior in plasma and tissue distributions. The ratios of tissue per plasma for total ADM and for ADM values in the liver, kidney and heart showed a two-digit magnitude each time they were examined. Twenty four h later, the ratios for ADM values in the liver, kidney, heart and lung were at high levels; 43.1, 48.1, 57.9 and 45.5 times, respectively. Twenty min after injection the ratios for total ADM values in the spleen, lung and tumors were comparatively small, but 24 h later, the ratio had increased 36.5, 45.5 and 6.8 times respectively.

  4. Histogram analysis of pharmacokinetic parameters by bootstrap resampling from one-point sampling data in animal experiments.

    Science.gov (United States)

    Takemoto, Seiji; Yamaoka, Kiyoshi; Nishikawa, Makiya; Takakura, Yoshinobu

    2006-12-01

    A bootstrap method is proposed for assessing statistical histograms of pharmacokinetic parameters (AUC, MRT, CL and V(ss)) from one-point sampling data in animal experiments. A computer program, MOMENT(BS), written in Visual Basic on Microsoft Excel, was developed for the bootstrap calculation and the construction of histograms. MOMENT(BS) was applied to one-point sampling data of the blood concentration of three physiologically active proteins ((111)In labeled Hsp70, Suc(20)-BSA and Suc(40)-BSA) administered in different doses to mice. The histograms of AUC, MRT, CL and V(ss) were close to a normal (Gaussian) distribution with the bootstrap resampling number (200), or more, considering the skewness and kurtosis of the histograms. A good agreement of means and SD was obtained between the bootstrap and Bailer's approaches. The hypothesis test based on the normal distribution clearly demonstrated that the disposition of (111)In-Hsp70 and Suc(20)-BSA was almost independent of dose, whereas that of (111)In-Suc(40)-BSA was definitely dose-dependent. In conclusion, the bootstrap method was found to be an efficient method for assessing the histogram of pharmacokinetic parameters of blood or tissue disposition data by one-point sampling.

  5. Use of a rapid HPLC assay for determination of pharmacokinetic parameters of ibuprofen in patients with cystic fibrosis.

    Science.gov (United States)

    Rifai, N; Sakamoto, M; Law, T; Galpchian, V; Harris, N; Colin, A A

    1996-11-01

    High doses of ibuprofen have been shown to delay the progression of lung disease without serious adverse effects in patients with cystic fibrosis. To be effective, peak ibuprofen concentration of 50 to 100 mg/L has to be achieved. We developed an HPLC assay to rapidly determine plasma ibuprofen concentration. We used this assay to determine the pharmacokinetics of ibuprofen in patients with cystic fibrosis. The assay possessed linearity up to 500 mg/L, sensitivity to 1 mg/L, average recovery of 98%, and run-to-run precision (n = 23) of 3%. Furthermore, the assay proved to be free of interference from 51 medications. Observed time to peak concentration varied significantly between those receiving ibuprofen tablets (mean + SD, 94 +/- 29 min, n = 16) and syrup (30 +/- 0 min, n = 4) (P < 0.0001). We conclude that the method described here is ideal for therapeutic monitoring of ibuprofen.

  6. Determination of gymnemagenin in rat plasma using high-performance liquid chromatography-tandem mass spectrometry: application to pharmacokinetics after oral administration of Gymnema sylvestre extract.

    Science.gov (United States)

    Kamble, Bhagyashree; Gupta, Ankur; Patil, Dada; Khatal, Laxman; Janrao, Shirish; Moothedath, Ismail; Duraiswamy, Basavan

    2013-05-01

    A sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed and validated for the determination of gymnemagenin (GMG), a triterpene sapogenin from Gymnema sylvestre, in rat plasma using withaferin A as the internal standard (IS). Plasma samples were simply extracted using liquid-liquid extraction with tetra-butyl methyl ether. Chromatographic separation was performed on Luna C(18) column using gradient elution of water and methanol (with 0.1% formic acid and 0.3% ammonia) at a flow rate of 0.8 mL/min. GMG and IS were eluted at 4.64 and 4.36 min, ionized in negative and positive mode, respectively, and quantitatively estimated using multiple reaction monitoring (MRM) mode. Two MRM transitions were selected at m/z 505.70 → 455.5 and m/z 471.50 → 281.3 for GMG and IS, respectively. The assay was linear over the concentration range of 5.280-300.920 ng/mL. The mean plasma extraction recoveries for GMG and IS were found to be 80.92 ± 8.70 and 55.63 ± 0.76%, respectively. The method was successfully applied for the determination of pharmacokinetic parameters of GMG after oral administration of G. sylvestre extract.

  7. LC-ESI-MS/MS method for quantification of ambrisentan in plasma and application to rat pharmacokinetic study.

    Science.gov (United States)

    Nirogi, Ramakrishna; Kandikere, Vishwottam; Komarneni, Prashanth; Aleti, Raghupathi; Padala, Nagasuryaprakash; Kalaikadhiban, Ilayaraja

    2012-10-01

    A sensitive high-performance liquid chromatography-positive ion electrospray tandem mass spectrometry method was developed and validated for the quantification of ambrisentan in plasma. The analyte and the internal standard (armodafinil) were extracted from plasma by acetonitrile precipitation and they were separated on a reversed-phase C(18) column with a gradient program. The MS acquisition was performed with multiple reaction monitoring mode using the respective [M + H](+) ions, m/z 379-347 for ambrisentan and m/z 274-167 for the IS. The assay exhibited a linear dynamic range of 1-2000 ng/mL for ambrisentan in plasma. Acceptable precision (<10%) and accuracy (100 ± 8%) were obtained for concentrations over the standard curve range. The method was successfully applied to quantify ambrisentan concentrations in a rodent pharmacokinetic study after a single oral administration of ambrisentan at 2.5 mg/kg to rats. Following oral administration the maximum mean concentration in plasma (C(max) ; 1197 ± 179 ng/mL) was achieved at 1.0 ± 0.9 h (T(max) ), and the area under the curve (AUC) was 6013 ± 997 ng h/mL. Therefore, development of such a simple and sensitive method in rat plasma should translate into a method for ambrisentan in human plasma for clinical trials.

  8. Study on spatial distribution of plasma parameters in a magnetized inductively coupled plasma

    Energy Technology Data Exchange (ETDEWEB)

    Cheong, Hee-Woon; Lee, Woohyun; Kim, Ji-Won; Whang, Ki-Woong, E-mail: kwhang@snu.ac.kr [Plasma Laboratory, Inter-University Semiconductor Research Center, Department of Electrical and Computer Engineering, Seoul National University, Seoul 151-742 (Korea, Republic of); Kim, Hyuk [Samsung Electronics Co., Banwol-dong, Hwaseong 445-701 (Korea, Republic of); Park, Wanjae [Tokyo Electron Miyagi Ltd., Taiwa-cho, Kurokawa-gun, Miyagi 981-3629 (Japan)

    2015-07-15

    Spatial distributions of various plasma parameters such as plasma density, electron temperature, and radical density in an inductively coupled plasma (ICP) and a magnetized inductively coupled plasma (M-ICP) were investigated and compared. Electron temperature in between the rf window and the substrate holder of M-ICP was higher than that of ICP, whereas the one just above the substrate holder of M-ICP was similar to that of ICP when a weak (<8 G) magnetic field was employed. As a result, radical densities in M-ICP were higher than those in ICP and the etch rate of oxide in M-ICP was faster than that in ICP without severe electron charging in 90 nm high aspect ratio contact hole etch.

  9. Method development for quantification of the environmental neurotoxin annonacin in Rat plasma by UPLC-MS/MS and application to a pharmacokinetic study.

    Science.gov (United States)

    Bonneau, Natacha; Schmitz-Afonso, Isabelle; Brunelle, Alain; Touboul, David; Champy, Pierre

    2015-11-01

    Annonacin is an environmental neurotoxin identified in the pulp of several fruits of the Annonaceae family (for example in Annona muricata, Asimina triloba), whose consumption was linked with the occurrence of sporadic atypical Parkinsonism with dementia. Pharmacokinetic parameters of this molecule are unknown. A method for its quantification in Rat plasma was developed, using its analogue annonacinone as an internal standard. Extraction from plasma was performed using ethylacetate with a good recovery. Quantification was performed by UPLC-MS/MS in SRM mode, based on the loss of the γ-methyl-γ-lactone (-112amu) from the sodium-cationized species [M+Na](+) of both annonacin and internal standard. The limit of quantification was 0.25ng/mL. Despite strong matrix effects, a good linearity was obtained over two distinct ranges 0.25-10ng/mL and 10-100ng/mL. The intra- and inter-day precisions (RSD) were lower than 10%, while accuracy was within ±10%. This method was applied to a pharmacokinetic study in the Rat. After oral administration of 10mg/kg annonacin, a Cmax of 7.9±1.5ng/mL was reached at Tmax 0.25h; T1/2 was 4.8±0.7h and apparent distribution volume was 387.9±64.6L. The bioavailability of annonacin was estimated to be 3.2±0.3% of the ingested dose.

  10. [Effects of multiple-trough sampling design and algorithm on the estimation of population and individual pharmacokinetic parameters].

    Science.gov (United States)

    Ling, Jing; Qian, Li-Xuan; Ding, Jun-Jie; Jiao, Zheng

    2014-05-01

    The purpose of this study is to investigate the effects of multiple-trough sampling design and nonlinear mixed effect modeling (NONMEM) algorithm on the estimation of population and individual pharmacokinetic parameters. Oxcarbazepine and tacrolimus were used as one-compartment and two-compartment model drugs, respectively. Seven sampling designs were investigated using various number of trough concentrations per individual ranging from 1-4. Monte Carlo simulations were performed to produce state-steady trough concentrations. One-compartment model was used to fit simulated data from oxcarbazepine and tacrolimus. The accuracy and precision of the estimated parameters were evaluated using the median prediction error (PE), the median absolute PE and boxplot. The results indicated that trough concentrations could yield reliable estimates of apparent clearance (CL/F). For oxcarbazepine, as the number of trough concentrations per subject increased, the accuracy and precision of CL/F, between-subject variability (BSV) of CL/F and residual variability (RUV) tended to be improved. For tacrolimus, however, although no improvement were observed in the accuracy of CL/F and BSV of CL/F, the PE distribution ranges were significantly narrowed and the RUV estimates were less bias and imprecise. In terms of algorithm, Monte Carlo importance sampling (IMP) and IMP assisted by mode a posteriori estimation (IMPMAP) were consistently better than other methods. Additionally, the sampling design had no significant effects on the individual parameter estimates, which were only depended on the interaction between BSV and RUV in various algorithms. Decreased in BSV and RUV levels can improve the accuracy and precision of the estimation for both population and individual pharmacokinetic parameter estimates.

  11. Possible impact of the CYP2D6*10 polymorphism on the nonlinear pharmacokinetic parameter estimates of paroxetine in Japanese patients with major depressive disorders

    Directory of Open Access Journals (Sweden)

    Saruwatari J

    2014-04-01

    Full Text Available Junji Saruwatari,1 Hiroo Nakashima,1 Shoko Tsuchimine,2 Miki Nishimura,1 Naoki Ogusu,1 Norio Yasui-Furukori21Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan; 2Department of Neuropsychiatry, Graduate School of Medicine, Hirosaki University, Hirosaki, JapanAbstract: It has been suggested that the reduced function allele with reduced cytochrome P450 (CYP 2D6 activity, CYP2D6*10, is associated with the interindividual differences in the plasma paroxetine concentrations, but there is no data presently available regarding the influence of the CYP2D6*10 polymorphism on the pharmacokinetic parameters, eg, Michaelis–Menten constant (Km and maximum velocity (Vmax, in Asian populations. The present study investigated the effects of the CYP2D6 polymorphisms, including CYP2D6*10, on the pharmacokinetic parameters of paroxetine in Japanese patients with major depressive disorders. This retrospective study included 15 Japanese patients with major depressive disorders (four males and eleven females who were treated with paroxetine. The CYP2D6*2, CYP2D6*4, CYP2D6*5, CYP2D6*10, CYP2D6*18, CYP2D6*39, and CYP2D6*41 polymorphisms were evaluated. A total of 56 blood samples were collected from the patients. The Km and Vmax values of paroxetine were estimated for each patient. The allele frequencies of CYP2D6*2, CYP2D6*4, CYP2D6*5, CYP2D6*10, CYP2D6*18, CYP2D6*39, and CYP2D6*41 were 6.7%, 0%, 10.0%, 56.7%, 0%, 26.7%, and 0%, respectively. The mean values of Km and Vmax were 50.5±68.4 ng/mL and 50.6±18.8 mg/day, respectively. Both the Km and Vmax values were significantly smaller in CYP2D6*10 allele carriers than in the noncarriers (24.2±18.3 ng/mL versus 122.5±106.3 ng/mL, P=0.008; 44.2±16.1 mg/day versus 68.3±15.0 mg/day, P=0.022, respectively. This is the first study to demonstrate that the CYP2D6*10 polymorphism could affect the nonlinear pharmacokinetic parameter estimates of

  12. Rapid HPLC-determination of ibuprofen and flurbiprofen in plasma for therapeutic drug control and pharmacokinetic applications.

    Science.gov (United States)

    Askholt, J; Nielsen-Kudsk, F

    1986-11-01

    Ibuprofen has wide applications in the treatment of rheumatoid arthritis and osteoarthroses as an effective non-steroidal antiinflammatory drug. The drug is still being investigated regarding its possible ability to reduce myocardial infarct size. The more potent biphenyl propionic analogue, flurbiprofen, has recently been introduced. Both drugs are strong inhibitors of cyclooxygenase. The specific HPLC-method described requires plasma samples of 100 microliter which are deproteinized and simultaneously extracted with acetonitrile containing either of the drugs as internal standard. Aliquots of 25 microliter of this primary extract were directly injected on a mu Bondapack C18 column. For elution was used a mixture of 60% methanol and 40% 50 mM phosphate buffer adjusted to pH 4.6. The detection limit (at 214 nm) for both drugs corresponded to plasma concentrations of about 0.2 micrograms X ml-1. The applicability of the method was demonstrated in a pharmacokinetic ibuprofen experiment in an adult person.

  13. Simultaneous Quantification of Diazepam and Dexamethasone in Plasma by High-Performance Liquid Chromatography with Tandem Mass Spectrometry and Its Application to a Pharmacokinetic Comparison between Normoxic and Hypoxic Rats

    Directory of Open Access Journals (Sweden)

    Wenwen Gong

    2015-04-01

    Full Text Available In order to investigate the pharmacokinetics of a combination of diazepam and dexamethasone under hypoxic conditions, a novel, sensitive and specific liquid chromatography with tandem mass spectrometry (LC-MS/MS method for the simultaneous determination of diazepam and dexamethasone in rat plasma was developed and validated. The chromatographic separation of analytes was successfully achieved on an XTerra® MS C18 column using a gradient elution of methanol and water containing 0.1% formic acid at a flow rate of 0.5 mL/min. This method demonstrated good linearity and no endogenous material interferences. The linear ranges were 1.0–100 ng/mL for diazepam and 2.0–200 ng/mL for dexamethasone. The intra- and inter-day precision for the two compounds in plasma were lower than 10.0%, and the accuracy was between −7.9% and 11.5%. Our method was then successfully applied in a pharmacokinetic comparison between normoxic and hypoxic rats. The results indicated that there were significant differences in the main pharmacokinetics parameters of diazepam and dexamethasone between normoxic and hypoxic rats. The results provide the important and valuable information for discovering and developing novel anti-hypoxia drug combinations, as well as a better understanding of the safety and efficacy of these drugs.

  14. Simultaneous Quantification of Diazepam and Dexamethasone in Plasma by High-Performance Liquid Chromatography with Tandem Mass Spectrometry and Its Application to a Pharmacokinetic Comparison between Normoxic and Hypoxic Rats.

    Science.gov (United States)

    Gong, Wenwen; Liu, Shuhong; Xu, Pingxiang; Fan, Ming; Xue, Ming

    2015-04-16

    In order to investigate the pharmacokinetics of a combination of diazepam and dexamethasone under hypoxic conditions, a novel, sensitive and specific liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of diazepam and dexamethasone in rat plasma was developed and validated. The chromatographic separation of analytes was successfully achieved on an XTerra® MS C18 column using a gradient elution of methanol and water containing 0.1% formic acid at a flow rate of 0.5 mL/min. This method demonstrated good linearity and no endogenous material interferences. The linear ranges were 1.0-100 ng/mL for diazepam and 2.0-200 ng/mL for dexamethasone. The intra- and inter-day precision for the two compounds in plasma were lower than 10.0%, and the accuracy was between -7.9% and 11.5%. Our method was then successfully applied in a pharmacokinetic comparison between normoxic and hypoxic rats. The results indicated that there were significant differences in the main pharmacokinetics parameters of diazepam and dexamethasone between normoxic and hypoxic rats. The results provide the important and valuable information for discovering and developing novel anti-hypoxia drug combinations, as well as a better understanding of the safety and efficacy of these drugs.

  15. Simultaneous determination of harmine, harmaline and their metabolites harmol and harmalol in beagle dog plasma by UPLC-ESI-MS/MS and its application to a pharmacokinetic study.

    Science.gov (United States)

    Zhang, Lei; Teng, Liang; Gong, Can; Liu, Wei; Cheng, Xuemei; Gu, Shenghua; Deng, Zhongping; Wang, Zhengtao; Wang, Changhong

    2013-11-01

    Harmine (HAR) and harmaline (HAL) were metabolized by demethylation to form harmol (HOL) and harmalol (HAM) both in vivo and in vitro. It has been demonstrated tremendous value of HAR, HAL and their metabolites in the therapy of Alzheimer's disease. A rapid, selective and sensitive UPLC-ESI-MS/MS method was firstly developed and validated for the simultaneous determination of HAR, HAL, HOL, and HAM in beagle dog plasma with 9-aminoacridine as the internal standard (IS). After protein precipitation with acetonitrile, the analytes were separated within 4.5 min on an ACQUITY UPLC BEH C18 column with a gradient elution system composed of 0.1% formic acid and acetonitrile at a flow rate of 0.4 ml/min. Detection was performed using multiple reactions monitoring mode under a positive ionization condition. The calibration curves of four analytes showed good linearity (r(2)>0.9959) within the tested concentration ranges. The low limit of quantification for HAR, HAL, HOL, and HAM were all 1.00 ng/ml. The mean accuracy of the analytes was within the range of 94.56-112.23%, the R.S.D. values of intra-day and the inter-day precision were less than 6.26% and 7.51%, respectively. Matrix effects and extraction recoveries of the analytes from the beagle dog plasma were within the range of 94.48-105.77% and 89.07-101.44%, respectively. The validated method was successfully applied to a pharmacokinetic study of HAR, HAL, HOL, and HAM in beagle dogs after intravenous administration of HAR and HAL both of 1.0mg/kg. The main pharmacokinetic parameters of Cmax, Vd, CL, AUC and MRT, except Ke and t1/2 values, showed significant difference between the two parent drug HAR and HAL, respectively (p<0.05-0.001). Because of the different metabolic rate of HAR and HAL in vivo, the two metabolites, HOL and HAM, exhibited unique pharmacokinetic properties.

  16. Plasma Processes : Sheath and plasma parameters in a magnetized plasma system

    Indian Academy of Sciences (India)

    Bornali Singha; A Sharma; J Chutia

    2000-11-01

    The variation of electron temperature and plasma density in a magnetized 2 plasma is studied experimentally in presence of a grid placed at the middle of the system. Plasma leaks through the negatively biased grid from the source region into the diffused region. It is observed that the electron temperature increases with the magnetic field in the diffused region whereas it decreases in the source region of the system for a constant grid biasing voltage. Also, investigation is done to see the change of electron temperature with grid biasing voltage for a constant magnetic field. This is accompanied by the study of the variation of sheath structure across the grid for different magnetic field and grid biasing voltage as well. It reveals that with increasing magnetic field and negative grid biasing voltage, the sheath thickness expands.

  17. An LC/MS quantitative and microdialysis method for cyclovirobuxine D pharmacokinetics in rat plasma and brain: The pharmacokinetic comparison of three different drug delivery routes.

    Science.gov (United States)

    Wei, Jia-bao; Lai, Qiao; Shumyak, Stepan P; Xu, Lan-fang; Zhang, Chen-xue; Ling, Jia-jun; Yu, Yang

    2015-10-01

    To explore the brain-targeting of cyclovirobuxine D(CVB-D) after administered intranasally, the pharmacokinetics of CVB-D via three different drug delivery routes: intragastric (i.g.), intranasal (i.n.), and intravenous (i.v.) in rat brain and blood was compared. Firstly, an in vivo microdialysis method for sampling CVB-D in both plasma and brain of the rat was established. Secondly, a liquid chromatography-tandem mass spectrometry method has been developed and validated for determination of CVB-D in microdialysis samples. For plasma and brain microdialysis samples, liquid-liquid extraction was used and donepezil was chosen as internal standard. Both were followed by HPLC separation and positive electrospray ionization tandem mass spectrometry detection (ESI-MS/MS). Chromatographic separation was achieved on a agilent C18 column with a mobile phase of methanol-water (50:50, v/v) (pH 3.2) containing 0.1% formic acid and 5mM ammonium acetate. Mass spectrometric detection in the positive ion mode was carried out by selected reaction monitoring (MRM) of the transitions at m/z 403.4→372.3 for CVB-D and m/z 380.2→243.1 for donepezil (IS). Good linearities were obtained in the range of 10-4000ng/mL in rat microdialysates for CVB-D. The lowest limit of quantitation was 5ng/mL, with an extraction recovery >75%, and no significant matrix effects. Intra- and inter-day precisions were all oral delivery routes, which indicates that intranasal administration of CVB-D could be a promising approach for the treatment of cerebrovascular disease.

  18. Plasma pharmacokinetics and bioavailability of verticillin A following different routes of administration in mice using liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Wang, Jiang; Zhu, Xiaohua; Kolli, Shamala; Wang, Hongyan; Pearce, Cedric J; Oberlies, Nicholas H; Phelps, Mitch A

    2017-05-30

    Verticillin A is a natural product isolated from fungal cultures and has displayed potent antibiotic, antiviral, nematocidal, and anticancer properties in vitro. While in vivo studies have been limited due to sparse supply, the in vivo efficacy data that does exist demonstrates potent anti-tumor activity in murine cancer models. The current study aims to investigate the pharmacokinetics and bioavailability of verticillin A in mice to provide guidance for further efficacy assessment in mouse models. A sensitive and specific liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of verticillin A in mouse plasma. Sample preparation was accomplished through protein precipitation, and chromatographic separation was achieved on an Agilent Zorbax Extend C18 column with a security guard cartridge C8 using a binary gradient with mobile phase A (water/0.1% formic acid) and B (ACN/0.1% formic acid) at a flow rate of 400μl/min. Elution of verticillin A and internal standard, hesperetin, occurred at 4.87 and 2.06min, respectively. The total chromatographic run time was 8min, and the assay was linear in the concentration range of 1-1000nM. The within- and between day precisions and accuracy were in the range of 2.58-8.71 and 90-105%, respectively. The assay was applied to determine plasma drug concentration in a mouse pharmacokinetic study. It was found that intraperitoneal dosing of 3mg/kg resulted in high systemic exposure and achieved Cmax of 110nM with plasma concentrations sustained above 10nM for the 24-h duration of the study. Intravenous and oral dosing achieved observed Cmax of 73nM and 9nM, respectively. Oral dosing resulted in an approximate 9% bioavailability. Comparing with previously published in vitro studies that demonstrated verticillin A is active in the 20nM to 130nM range, the pharmacokinetic data demonstrate similar levels are achieved in mouse plasma via intravenous or intraperitoneal dosing routes

  19. Development and validation of limited-sampling strategies for predicting amoxicillin pharmacokinetic and pharmacodynamic parameters.

    Science.gov (United States)

    Suarez-Kurtz, G; Ribeiro, F M; Vicente, F L; Struchiner, C J

    2001-11-01

    Amoxicillin plasma concentrations (n = 1,152) obtained from 48 healthy subjects in two bioequivalence studies were used to develop limited-sampling strategy (LSS) models for estimating the area under the concentration-time curve (AUC), the maximum concentration of drug in plasma (C(max)), and the time interval of concentration above MIC susceptibility breakpoints in plasma (T>MIC). Each subject received 500-mg amoxicillin, as reference and test capsules or suspensions, and plasma concentrations were measured by a validated microbiological assay. Linear regression analysis and a "jack-knife" procedure revealed that three-point LSS models accurately estimated (R(2), 0.92; precision, MICs of 0.25 or 2.0 microg/ml, which are representative of microorganisms susceptible and resistant to amoxicillin.

  20. Pharmacokinetics of piperacillin and tazobactam in plasma and subcutaneous interstitial fluid in critically ill patients receiving continuous venovenous haemodiafiltration.

    Science.gov (United States)

    Varghese, Julie M; Jarrett, Paul; Boots, Robert J; Kirkpatrick, Carl M J; Lipman, Jeffrey; Roberts, Jason A

    2014-04-01

    This prospective pharmacokinetic study aimed to describe plasma and interstitial fluid (ISF) pharmacokinetics of piperacillin and tazobactam in critically ill patients on continuous venovenous haemodiafiltration (CVVHDF). Piperacillin/tazobactam (4g/0.5g) was administered every 8h and CVVHDF was performed as a 3-3.5L/h exchange using a polyacrylonitrile filter with a surface area of 1.05m(2). Serial blood (pre- and post-filter), filtrate/dialysate, urine and ISF concentrations were measured. Subcutaneous tissue ISF concentrations were determined using microdialysis. A total of 407 samples were collected. Median peak plasma concentrations were 210.5 (interquartile range=161.5-229.0) and 29.4 (27.9-32.0) mg/L and median trough plasma concentrations were 64.3 (49.0-68.9) and 12.3 (7.7-13.7) mg/L for piperacillin and tazobactam, respectively. The plasma elimination half-life was 6.4 (4.6-8.7) and 7.3 (4.6-11.8) h, volume of distribution 0.42 (0.29-0.49) and 0.32 (0.24-0.36) L/kg, total clearance 5.1 (4.2-6.2) and 3.8 (3.3-4.2) L/h and CVVHDF clearance 2.5 (2.3-3.1) and 2.5 (2.3-3.2) L/h for piperacillin and tazobactam, respectively. The tissue penetration ratio or ratio of area under the concentration-time curve of the unbound drug in ISF to plasma (unbound AUCISF/AUCplasma) was ca. 1 for both piperacillin and tazobactam. This is the first report of concurrent plasma and ISF concentrations of piperacillin and tazobactam during CVVHDF. For the CVVHDF settings used in this study, a dose of 4.5g piperacillin/tazobactam administered evry 8h resulted in piperacillin concentrations in plasma and ISF >32mg/L throughout most of the dosing interval. Copyright © 2014. Published by Elsevier B.V.

  1. Plasma pharmacokinetics and urinary excretion of isoflavones after ingestion of soy products with different aglycone/glucoside ratios in South Korean women.

    Science.gov (United States)

    Chang, Youngeun; Choue, Ryowon

    2013-10-01

    Asian populations are thought to receive significant health benefits from traditional diets rich in soybeans due to high isoflavone contents. However, available epidemiologic data only weakly support this hypothesis. The present study was carried out to assess the pharmacokinetics of isoflavones in South Korean women after ingestion of soy-based foods. Twenty-six healthy female volunteers (20-30 y old) consumed three different soy products (i.e., isogen, soymilk, and fermented soybeans) with different aglycone/glucoside ratios. Plasma and urine isoflavone concentrations were measured by high-performance liquid chromatography (HPLC) after ingestion of one of the soy products. Pharmacokinetic parameters were determined using the WinNonlin program. The area under the curve (AUC) for plasma daidzein levels of the soymilk group (2,101 ± 352 ng · h/mL) was significantly smaller than those of the isogen (2,628 ± 573 ng · h/mL) and fermented soybean (2,593 ± 465 ng · h/mL) groups. The maximum plasma concentration (Cmax ) of daidzein for the soymilk group (231 ± 44 ng/mL) was significantly higher than those of the isogen (160 ± 32 ng/mL) and fermented soybean (195 ± 35 ng/mL) groups. The half-lives of daidzein and genistein in the soymilk group (5.9 and 5.6 h, respectively) were significantly shorter than those in the individuals given isogen (9.6 and 8.5 h, respectively) or fermented soybean (9.5 and 8.2 h, respectively). The urinary recovery rates of daidzein and genistein were 42% and 17% for the isogen group, 46% and 23% for the fermented soybean group, and 33% and 22% for the soymilk group. In conclusion, our data indicated that soy products containing high levels of isoflavone aglycone are more effective for maintaining plasma isoflavone concentrations. Additional dose-response, durational, and interventional studies are required to evaluate the ability of soy-based foods to increase the bioavailability of isoflavones that positively affect human health.

  2. A study on plasma parameters in Ar/SF6 inductively coupled plasma

    Science.gov (United States)

    Oh, Seung-Ju; Lee, Hyo-Chang; Chung, Chin-Wook

    2017-01-01

    Sulfur hexafluoride (SF6) gas or Ar/SF6 mixing gas is widely used in plasma processes. However, there are a little experimental studies with various external parameters such as gas pressure and mixing ratio. In this work, a study of the plasma parameters by changing the gas mixing ratio was done in an Ar/SF6 inductively coupled plasma from the measurement of the electron energy distribution function. At a low gas pressure, as the mixing ratio of SF6 gas increased at a fixed inductively coupled plasma (ICP) power, the electron density decreased and the electron temperature increased, while they were not changed drastically. At a high gas pressure, a remarkable increase in the electron temperature was observed with the decrease in the electron density. These variations are due to the electron loss reactions such as the electron attachment. It was also found that at a fixed ICP power, the negative ion creation with the diluted SF6 gas can change the discharge mode transition from an inductive mode to a capacitive mode at the high gas pressure. The electron attachment reactions remove the low energy electrons and change the mean electron energy towards higher energies with diluting SF6 gas at high pressure. The measured results were compared with the simplified global model, and the global model is in relatively good agreement with the measured plasma parameters except for the result in the case of the large portion of SF6 gas at the high pressure and the capacitive mode, which causes strong negative ion formation by the electron attachment reactions.

  3. Enrofloxacin and marbofloxacin in horses: comparison of pharmacokinetic parameters, use of urinary and metabolite data to estimate first-pass effect and absorbed fraction.

    Science.gov (United States)

    Peyrou, M; Bousquet-Melou, A; Laroute, V; Vrins, A; Doucet, M Y

    2006-10-01

    Enrofloxacin and marbofloxacin are two veterinary fluoroquinolones used to treat severe bacterial infections in horses. A repeated measures study has been designed to compare their pharmacokinetic parameters, to investigate their bioavailability and to estimate their absorbed fraction and first-pass effect by using plasma, urinary and metabolite data collected from five healthy mares. Clearance and V(d(ss)) were greater for enrofloxacin (mean +/- SD = 6.34 +/- 1.5 mL/min/kg and 2.32 +/- 0.32 L/kg, respectively) than for marbofloxacin (4.62 +/- 0.67 mL/min/kg and 1.6 +/- 0.25 L/kg, respectively). Variance of the AUC(0-inf) of marbofloxacin was lower than that for enrofloxacin, with, respectively, a CV = 15% and 26% intravenously and a CV = 31% and 55% after oral administration. Mean oral bioavailability was not significantly different between marbofloxacin (59%) and enrofloxacin (55%). The mean percentage of the dose eliminated unchanged in urine was significantly higher for marbofloxacin (39.7%) than that for enrofloxacin (3.4%). Absorbed fraction and first-pass effect were only determinable for enrofloxacin, whereas the percentage of the dose absorbed in the portal circulation was estimated to be 78% and the fraction not extracted during the first pass through the liver was 65%. Consequently, the moderate observed bioavailability of enrofloxacin appears to be mainly caused by hepatic first-pass effect.

  4. Evolution of plasma parameters in a He - N2/Ar magnetic pole enhanced inductive plasma source

    Science.gov (United States)

    Younus, Maria; Rehman, N. U.; Shafiq, M.; Zakaullah, M.; Abrar, M.

    2016-02-01

    A magnetic pole enhanced inductively coupled H e - N2/A r plasma is studied at low pressure, to monitor the effects of helium mixing on plasma parameters like electron number density (ne) , electron temperature (Te) , plasma potential (Vp ) , and electron energy probability functions (EEPFs). An RF compensated Langmuir probe is employed to measure these plasma parameters. It is noted that electron number density increases with increasing RF power and helium concentration in the mixture, while it decreases with increase in filling gas pressure. On the other hand, electron temperature shows an increasing trend with helium concentration in the mixture. At low RF powers and low helium concentration in the mixture, EEPFs show a "bi-Maxwellian" distribution with pressure. While at RF powers greater than 50 W and higher helium concentration in the mixture, EEPFs evolve into "Maxwellian" distribution. The variation of skin depth with RF power and helium concentration in the mixture, and its relation with EEPF are also studied. The effect of helium concentrations on the temperatures of two electron groups ( Tb u l k and Tt a i l ) in the "bi-Maxwellian" EEPFs is also observed. The temperature of low energy electron group ( Tb u l k) shows significant increase with helium addition, while the temperature of tail electrons ( Tt a i l) increases smoothly as compared to ( Tb u l k).

  5. Optimization and validation of a fast RP-HPLC method for the determination of dobutamine in rat plasma:Pharmacokinetic studies in healthy rat subjects

    Institute of Scientific and Technical Information of China (English)

    Ramesh Thippani; Nageswara Rao Pothuraju; Nageswara Rao Ramisetti; Saida Shaik

    2013-01-01

    A novel isocratic reverse phase high performance liquid chromatography (RP-HPLC) with photo diode array (PDA) detection method for the determination of dobutamine (DBT) in rat plasma was developed and validated after optimization of various chromatographic conditions and other experimental parameters. Homoveratrylamine was used as an internal standard. Methanol was used as the extracting solvent for the preparation of plasma samples. Samples were separated on a Symmetry C18 (250 mm ? 4.6 mm i.d., 5μm) analytical column. Acetonitrile and 15 mM potassium dihydrogen phosphate (pH 5.0 with 0.3%TEA) (20:80, v/v) was used. The column oven temperature was optimized at 35 1C and the flow rate was 0.8 mL/min. The detection wavelength was fixed at 230 nm for entire analysis. The calibration curve was found to be linear over the concentration range of 50-2000 ng/mL (r2 ¼ 0.9992). The limit of quantification (LOQ) of the method was 50 ng/mL. The % RSD values of accuracy and precision values for intra and inter days were o15%at quality control (QC) concentrations. Recovery, stability and robustness were studied within the acceptable range according to ICH guidelines. The method was efficiently applied to a pharmacokinetic study in healthy Wistar rats.

  6. Safety, Pharmacokinetics, Pharmacodynamics, and Plasma Lipoprotein Distribution of Eritoran (E5564) during Continuous Intravenous Infusion into Healthy Volunteers

    Science.gov (United States)

    Rossignol, Daniel P.; Wasan, Kishor M.; Choo, Eugene; Yau, Edwin; Wong, Nancy; Rose, Jeffrey; Moran, Jeffrey; Lynn, Melvyn

    2004-01-01

    Eritoran, a structural analogue of the lipid A portion of lipopolysaccharide (LPS), is an antagonist of LPS in animal and human endotoxemia models. Previous studies have shown that low doses (350 to 3,500 μg) of eritoran have demonstrated a long pharmacokinetic half-life but a short pharmacodynamic half-life. The present study describes the safety, pharmacokinetics and pharmacodynamics, and lipid distribution profile of eritoran during and after a 72-h intravenous infusion of 500, 2,000, or 3,500 μg/h into healthy volunteers. Except for the occurrence of phlebitis, eritoran administration over 72 h was safe and well tolerated. Eritoran demonstrated a slow plasma clearance (0.679 to 0.930 ml/h/kg of body weight), a small volume of distribution (45.6 to 49.8 ml/kg), and a relatively long half-life (50.4 to 62.7 h). In plasma, the majority (∼55%) of eritoran was bound to high-density lipoproteins. During infusion and for up to 72 h thereafter, ex vivo response of blood to 1- or 10-ng/ml LPS was inhibited by ≥85%, even when the lowest dose of eritoran (500 μg/h) was infused. Inhibition of response was dependent on eritoran dose and the concentration of LPS used as an agonist. Finally, in vitro analysis with purified lipoprotein and protein fractions from plasma obtained from healthy volunteers indicated that eritoran is inactivated by high-density but not low-density lipoproteins, very-low-density lipoproteins, or albumin. From these results, we conclude that up to 252 mg of eritoran can be safely infused into normal volunteers over 72 h and even though it associates extensively with high-density lipoproteins, antagonistic activity is maintained, even after infusion ceases. PMID:15328078

  7. A Rapid and Sensitive HPLC Method for the Analysis of Celecoxib in Human Plasma: Application to Pharmacokinetic Studies

    Directory of Open Access Journals (Sweden)

    A Ajami

    2008-09-01

    Full Text Available Background and the purpose of the study: A suitable high-performance liquid chromatography (HPLC method for determination of celecoxib levels in plasma is of prime need for the pharmacokinetics and bioequivalence studies of celecoxib preparations. The present study describes a simple, rapid, sensitive, reliable, and economic HPLC method for determination of celecoxib in human plasma which is more feasible than reported celecoxib HPLC assays. Methods: The drug and internal standard were extracted using n-hexane /isoamyl alcohol (97:3 and analyzed on a C18 µ-Bondapak HPLC column with KH2PO4 (0.01M, pH= 4 - acetonitrile (60:40 as the mobile phase, at 260 nm. The method involved simple one-step liquid-liquid extraction procedure with extraction recovery of greater than 90%. Results:  The standard curve covering 0.01-2.0 μg/ml concentration range was linear. The coefficients of variation and relative errors for inter- and intra-day assay ranged from 5.67 to 9.83 and 0.35 to 7.89 %, respectively. Conclusions: HPLC assay was performed isocratically on a reversed-phase column with UV detection. By this method a limit of quantification of 10 ng/ml of a sample size of 0.5 ml is achieved which is comparable or even better than the reported methods. The developed method was applied to the analysis of celecoxib levels in plasma collected from healthy volunteers who participated in a pharmacokinetic study.

  8. Plasma pharmacokinetics of once- versus twice-daily lamivudine and abacavir: simplification of combination treatment in HIV-1-infected children (PENTA-13).

    NARCIS (Netherlands)

    Bergshoeff, A.S.; Burger, D.M.; Verweij, C.; Farrelly, L.; Flynn, J.; Prevost, M. Le; Walker, S.; Novelli, V.; Lyall, H.; Khoo, S.; Gibb, D.

    2005-01-01

    BACKGROUND: There are few data on plasma and intracellular pharmacokinetics (PK) of once-daily (q24h) nucleoside analogues in HIV-infected children. METHODS: Children aged 2-13 years receiving combination treatment containing lamivudine (3TC) (4 mg/kg) and/or abacavir (ABC) (8 mg/kg) twice daily (q1

  9. The effect of plasma operating parameters on analyte signals in inductively coupled plasma-mass spectrometry

    Science.gov (United States)

    Horlick, G.; Tan, S. H.; Vaughan, M. A.; Rose, C. A.

    Utilizing the SCIEX ICP-MS an extensive study of the effects that plasma operating parameters have on analyte ion signals in ICP-MS has been carried out. Parameters studied included aerosol flow rate (nebulizer pressure), auxiliary flow rate, power and sampling depth (sampling position from the load coil). The two key parameters are aerosol flow rate (nebulizer pressure) and power. Elements can be grouped into characteristic behaviour patterns based on the overall dependence of their ion count signal on these two parameters. The nebulizer pressure-power behavior patterns allow a sensible selection of compromise operating conditions and significantly clarify single parameter observations which often indicate confusing trends in behavior. In addition to characterizing analyte ion signals the parameter behavior plots have also been used to study oxide species and plus two ions in ICP-MS. While aerosol flow rate and power appear to be the key ICP parameters in ICP-MS, ion signals are dependent on sampling depth and auxiliary flow rate and some data are also presented illustrating the signal dependence on these two parameters.

  10. Ethanol-drug absorption interaction: potential for a significant effect on the plasma pharmacokinetics of ethanol vulnerable formulations.

    Science.gov (United States)

    Lennernäs, Hans

    2009-01-01

    Generally, gastric emptying of a drug to the small intestine is controlled by gastric motor activity and is the main factor affecting the onset of absorption. Accordingly, the emptying rate from the stomach is mainly affected by the digestive state, the properties of the pharmaceutical formulation and the effect of drugs, posture and circadian rhythm. Variability in the gastric emptying of drugs is reflected in variability in the absorption rate and the shape of the plasma pharmacokinetic profile. When ethanol interacts with an oral controlled release product, such that the mechanism controlling drug release is impaired, the delivery of the dissolved dose into the small intestine and the consequent absorption may result in dangerously high plasma concentrations. For example, the maximal plasma concentration of hydromorphone has individually been shown to be increased as much as 16 times through in vivo testing as a result of this specific pharmacokinetic ethanol-drug formulation interaction. Thus, a pharmacokinetic ethanol-drug interaction is a very serious safety concern when substantially the entire dose from a controlled release product is rapidly emptied into the small intestine (dose dumping), having been largely dissolved in a strong alcoholic beverage in the stomach during a sufficient lag-time in gastric emptying. Based on the literature, a two hour time frame for screening the in vitro dissolution profile of a controlled release product in ethanol concentrations of up to 40% is strongly supported and may be considered as the absolute minimum standard. It is also evident that the dilution, absorption and metabolism of ethanol in the stomach are processes with a minor effect on the local ethanol concentration and that ethanol exposure will be highly dependent on the volume and ethanol concentration of the fluid ingested, together with the rate of intake and gastric emptying. When and in which patients a clinically significant dose dumping will happen is

  11. PHARMACOKINETIC PARAMETERS TO BE EVALUATED FOR SELECTED LOW MOLECULAR WEIGHT HEPARINs IN BIOEQUIVALENCE STUDIES

    Directory of Open Access Journals (Sweden)

    Chaitanya Gadiko*, Satyanarayana Thota and Sudhakar K. Tippabotla

    2012-11-01

    Full Text Available Bioequivalence needs to be established on healthy human volunteers for Low Molecular Weight Heparins (LMWHs such as Dalteparin, Enoxaparin, Tinzaparin and Fondaparinux using Pharmacodynamic marker(s for generic approval. Anti-Xa and anti-IIa activity are used to determine the activity of LMWHs (Dalteparin, Enoxaparin and Tinzaparin and anti-Xa activity for Fondaparinux in biological samples for the assessment of its bioavailability. These are selected based on the pharmacodynamic activities of LMWHs. LMWHs exhibit their antithrombotic activity preferentially by inhibiting clotting Factor Xa, and to a lesser extent Factor IIa. On the other hand Fondaparinux is a synthetic and specific inhibitor of Factor-Xa and hencebioequivalence needs to be established for only anti-Xa activity. The pharmacodynamic data of anti-IIa activity need to be submitted for regulatory agency as supportive data of comparable therapeutic outcome for all LMWHs except Fondaparinux. In addition to the above, pharmacokinetic data of Heptest (Heparin clotting assay and activated Partial Thromboplastin Time (aPTT may also serve as a supportive evidence for establishing bioequivalence of LMWH formulations as there were no clear recommendations available.

  12. PHARMACOKINETIC PARAMETERS OF VALPROIC ACID AND CARBAMAZEPINE FROM ROUTINELY COLLECTED DATA: INFLUENCE OF PATIENT CHARACTERISTICS

    Directory of Open Access Journals (Sweden)

    HASNAH IBRAHIM

    2008-01-01

    Full Text Available Individualising a drug dosage regimen is more appropriate if it is based on pharmacokinetics data derived from local populations. In this study, we estimated valproic acid (VPA and carbamazepine (CBZ clearances in the Malaysian population from routinely collected therapeutic drug monitoring (TDM data. We also evaluated the effects of gender, age, weight and concurrent antiepileptic drug (AED therapy on VPA and CBZ clearance. Data was collected retrospectively from TDM forms of adult patients. Apparent drug clearance was estimated based on the standard steady state clearance equation. Mann-Whitney and Kruskal-Wallis tests were used to evaluate gender and therapy differences, while Spearman’s Rank correlation was used to determine the associations of age and weight with clearance. One hundred thirty-two samples for VPA and 67 for CBZ were included in the analysis. Patients’ ages ranged from 15 to 72 years old. Mean VPA and CBZ clearances were found to be 0.36 l/kg/d and 1.60 l/kg/d, respectively. VPA clearance correlated positively but poorly with weight. Our results showed significant differences in (i VPA clearance among male and female patients and (ii VPA clearance between monotherapy and combination therapy. These findings provide a guide to initiate maintenance doses of VPA and CBZ in our local patients. Awareness of factors influencing drug clearance should help to optimise patients’ dosing regimens.

  13. A UFLC-MS/MS method with a switching ionization mode for simultaneous quantitation of polygalaxanthone III, four ginsenosides and tumulosic acid in rat plasma: application to a comparative pharmacokinetic study in normal and Alzheimer's disease rats.

    Science.gov (United States)

    Lv, Chunxiao; Li, Qing; Zhang, Yaowen; Sui, Zhenyu; He, Bosai; Xu, Huarong; Yin, Yidi; Chen, Xiaohui; Bi, Kaishun

    2013-08-01

    A fast, sensitive and reliable ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method has been developed and validated for simultaneous quantitation of polygalaxanthone III (POL), ginsenoside Rb1 (GRb1), ginsenoside Rd (GRd), ginsenoside Re (GRe), ginsenoside Rg1 (GRg1) and tumulosic acid (TUM) in rat plasma after oral administration of Kai-Xin-San, which plays an important role for the treatment of Alzheimer's disease (AD). The plasma samples were extracted by liquid-liquid extraction using ethyl acetate-isopropanol (1:1, v/v) with salidrdoside as internal standard (IS). Good chromatographic separation was achieved using gradient elution with the mobile phase consisting of methanol and 0.01% acetic acid in water. The tandem mass spectrometric detection was performed in multiple reaction monitoring mode on 4000Q UFLC-MS/MS system with turbo ion spray source in a negative and positive switching ionization mode. The lower limits of quantification were 0.2-1.5 ng/ml for all the analytes. Both intra-day and inter-day precision and accuracy of analytes were well within acceptance criteria (±15%). The mean absolute extraction recoveries of analytes and IS from rat plasma were all more than 60.0%. The validated method has been successfully applied to comparing pharmacokinetic profiles of analytes in normal and AD rat plasma. The results indicated that no significant differences in pharmacokinetic parameters of GRe, GRg1 and TUM were observed between the two groups, while the absorption of POL and GRd in AD group were significantly higher than those in normal group; moreover, the GRb1 absorbed more rapidly in model group. The different characters of pharmacokinetics might be caused by pharmacological effects of the analytes.

  14. Human plasma concentrations of herbicidal carbamate molinate extrapolated from the pharmacokinetics established in in vivo experiments with chimeric mice with humanized liver and physiologically based pharmacokinetic modeling.

    Science.gov (United States)

    Yamashita, Masanao; Suemizu, Hiroshi; Murayama, Norie; Nishiyama, Sayako; Shimizu, Makiko; Yamazaki, Hiroshi

    2014-10-01

    To predict concentrations in humans of the herbicidal carbamate molinate, used exclusively in rice cultivation, a forward dosimetry approach was carried out using data from lowest-observed-adverse-effect-level doses orally administered to rats, wild type mice, and chimeric mice with humanized liver and from in vitro human and rodent experiments. Human liver microsomes preferentially mediated hydroxylation of molinate, but rat livers additionally produced molinate sulfoxide and an unidentified metabolite. Adjusted animal biomonitoring equivalents for molinate and its primary sulfoxide from animal studies were scaled to human biomonitoring equivalents using known species allometric scaling factors and human metabolic data with a simple physiologically based pharmacokinetic (PBPK) model. The slower disposition of molinate and accumulation of molinate sulfoxide in humans were estimated by modeling after single and multiple doses compared with elimination in rodents. The results from simplified PBPK modeling in combination with chimeric mice with humanized liver suggest that ratios of estimated parameters of molinate sulfoxide exposure in humans to those in rats were three times as many as general safety factor of 10 for species difference in toxicokinetics. Thus, careful regulatory decision is needed when evaluating the human risk resulting from exposure to low doses of molinate and related carbamates based on data obtained from rats.

  15. Population pharmacokinetics and relationship between demographic and clinical variables and pharmacokinetics of gentamicin in neonates

    NARCIS (Netherlands)

    Stolk, L M L; Degraeuwe, P L J; Nieman, F H M; de Wolf, M C; de Boer, A

    2002-01-01

    Population pharmacokinetic parameter estimates were calculated from 725 routine plasma gentamicin concentrations obtained in 177 neonates of 24 to 42 weeks' gestational age in their first week of life. Kel increases and V/W decreases with increasing gestational age. Almost identical results were obt

  16. A UPLC/MS/MS method for determination of protosappanin B in rat plasma and its application of a pharmacokinetic and bioavailability study.

    Science.gov (United States)

    Chen, Wei-Ying; Zhou, Xian-Zhen; Wu, Li-Lan; Wu, Yun-Shan; Wang, Shu-Mei; Liu, Bo; Guo, De-An

    2016-12-14

    Caesalpinia sappan L. is a traditional medicinal plant which is used for promoting blood circulation and cerebral apoplexy therapy in China. Previous reports showed that the extracts of Caesalpinia sappan L. could exert vasorelaxant activity and anti-inflammation activity. Protosappanin B is a major constituent of C. sappan L., and showed several important bioactivities. The separation was achieved by an Acquity UPLC BEH Symmetry Shield RP18 column (1.7 μm, 2.1 × 100 mm) column with the gradient mobile phase consisting of 5 mm ammonium acetate aqueous solution and acetonitrile. Detection was carried out by using negative-ion electrospray tandem mass spectrometry via multiple reaction monitoring. Plasma samples were preprocessed by an extraction with ethyl acetate, and apigenin was used as internal standard. The current UPLC-MS/MS assay was validated for linearity, accuracy, intraday and interday precisions, stability, matrix effects and extraction recovery. After oral and intravenous administration, the main pharmacokinetic parameters were as follows: peak concentrations, 83.5 ± 46.2 and 1329.6 ± 343.6 ng/mL; areas under the concentration-time curve, 161.9 ± 69.7 and 264.9 ± 56.3 μg h/L; and half-lives, 3.4 ± 0.9 and 0.3 ± 0.1 h, respectively. The absolute bioavailability in rats of protosappanin B was 12.2%. The method has been successfully applied to a pharmacokinetic and bioavailability study of protosappanin B in rats.

  17. Use of a probing pulsed magnetic field for determining plasma parameters

    Science.gov (United States)

    Rousskikh, A. G.; Oreshkin, V. I.; Zhigalin, A. S.; Yushkov, G. Yu.

    2016-11-01

    A novel, simple, and readily usable method is proposed for measuring the electrical conductivity and temperature of a plasma. The method is based on the interaction of the test plasma with a pulsed magnetic field. The electric signals induced by the magnetic field in the circuits of two probes (miniature solenoids), one immersed in the test plasma and the other placed outside the plasma, provide data for estimating the plasma parameters. The method was verified experimentally by determining the parameters of the plasma flows generated in the cathode spots high-current pulsed vacuum arcs that were used to form cylindrical shells of bismuth Z-pinch plasma.

  18. Use of unbound volumes of drug distribution in pharmacokinetic calculations.

    Science.gov (United States)

    Stepensky, David

    2011-01-18

    Volume of drug distribution is a primary pharmacokinetic parameter. This study assessed effects of drugs' plasma protein binding and tissue distribution on volume of drug distribution and identified the most appropriate ways for its calculation. Effects of the distribution factors on the unbound and total drug plasma concentrations and on the corresponding volumes of distribution were studied using pharmacokinetic modeling and simulation approach based on in vitro and in vivo concentration vs. time data of diazepam, a model drug with extensive plasma protein binding and tissue distribution. Pharmacokinetics of diazepam were appropriately described by three-compartment pharmacokinetic model that incorporated the processes of plasma protein binding and tissue permeation. According to this model, displacement of the drug from plasma proteins increases the unbound (but not the total) plasma concentrations and induces faster drug elimination from the body. The distribution pattern of the drug in the body and the time course of unbound (pharmacologically active) drug concentrations correlated with the unbound volumes of distribution, but not with the total volumes of distribution. In conclusion, unbound volumes of distribution appropriately describe the drug distribution pattern and the time course of unbound drug concentrations and are recommended for use as primary pharmacokinetic parameters in pharmaceutical research. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Gestation-Specific Changes in the Anatomy and Physiology of Healthy Pregnant Women: An Extended Repository of Model Parameters for Physiologically Based Pharmacokinetic Modeling in Pregnancy.

    Science.gov (United States)

    Dallmann, André; Ince, Ibrahim; Meyer, Michaela; Willmann, Stefan; Eissing, Thomas; Hempel, Georg

    2017-04-11

    In the past years, several repositories for anatomical and physiological parameters required for physiologically based pharmacokinetic modeling in pregnant women have been published. While providing a good basis, some important aspects can be further detailed. For example, they did not account for the variability associated with parameters or were lacking key parameters necessary for developing more detailed mechanistic pregnancy physiologically based pharmacokinetic models, such as the composition of pregnancy-specific tissues. The aim of this meta-analysis was to provide an updated and extended database of anatomical and physiological parameters in healthy pregnant women that also accounts for changes in the variability of a parameter throughout gestation and for the composition of pregnancy-specific tissues. A systematic literature search was carried out to collect study data on pregnancy-related changes of anatomical and physiological parameters. For each parameter, a set of mathematical functions was fitted to the data and to the standard deviation observed among the data. The best performing functions were selected based on numerical and visual diagnostics as well as based on physiological plausibility. The literature search yielded 473 studies, 302 of which met the criteria to be further analyzed and compiled in a database. In total, the database encompassed 7729 data. Although the availability of quantitative data for some parameters remained limited, mathematical functions could be generated for many important parameters. Gaps were filled based on qualitative knowledge and based on physiologically plausible assumptions. The presented results facilitate the integration of pregnancy-dependent changes in anatomy and physiology into mechanistic population physiologically based pharmacokinetic models. Such models can ultimately provide a valuable tool to investigate the pharmacokinetics during pregnancy in silico and support informed decision making regarding

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

    Institute of Scientific and Technical Information of China (English)

    Xiu-Man Sun; Qiong-Feng Liao; Yu-Ting Zhou; Xue-Jiao Deng; Zhi-Yong Xie

    2014-01-01

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

  1. Reversed phase HPLC determination of tamoxifen in dog plasma and its pharmaco-kinetics after a single oral dose administration

    Directory of Open Access Journals (Sweden)

    Davi Pereira de Santana

    2008-01-01

    Full Text Available The analytical method developed to evaluate tamoxifen in dog plasma samples was precise, accurate, robust and linear in the range of 5-200 ng/mL. The limits of detection and quantification were 0.981 ng/mL and 2.97 ng/mL, respectively. Besides, the intra-day precision and accuracy variations were 8.78 and 10.16%, respectively. Tamoxifen concentrations were analyzed by combined reversed phase liquid chromatography and UV detection (lambda=280 nm. The study was conducted using an open randomized 2-period crossover balanced design with a 1-week washout period between the doses. This simple, rapid and selective method is suitable for pharmacokinetic, bioavailability and bioequivalence studies.

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

    Directory of Open Access Journals (Sweden)

    Xiu-Man Sun

    2014-10-01

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

  3. Revisiting linear plasma waves for finite value of the plasma parameter

    Science.gov (United States)

    Grismayer, Thomas; Fahlen, Jay; Decyk, Viktor; Mori, Warren

    2010-11-01

    We investigate through theory and PIC simulations the Landau-damping of plasma waves with finite plasma parameter. We concentrate on the linear regime, γφB, where the waves are typically small and below the thermal noise. We simulate these condition using 1,2,3D electrostatic PIC codes (BEPS), noting that modern computers now allow us to simulate cases where (nλD^3 = [1e2;1e6]). We study these waves by using a subtraction technique in which two simulations are carried out. In the first, a small wave is initialized or driven, in the second no wave is excited. The results are subtracted to provide a clean signal that can be studied. As nλD^3 is decreased, the number of resonant electrons can be small for linear waves. We show how the damping changes as a result of having few resonant particles. We also find that for small nλD^3 fluctuations can cause the electrons to undergo collisions that eventually destroy the initial wave. A quantity of interest is the the life time of a particular mode which depends on the plasma parameter and the wave number. The life time is estimated and then compared with the numerical results. A surprising result is that even for large values of nλD^3 some non-Vlasov discreteness effects appear to be important.

  4. Determination of plasma topiramate concentration using LC-MS/MS for pharmacokinetic and bioequivalence studies in healthy Korean volunteers.

    Science.gov (United States)

    Park, Jin-Hee; Park, Yoo-Sin; Lee, Min-Ho; Rhim, Si-Youn; Song, Jae-Chul; Lee, Soo-Jin; Kim, Jung-Mogg; Shaw, Leslie M; Kang, Ju-Seop

    2008-08-01

    A rapid, simple and validated liquid chromatography coupled to tandem mass spectrometric method (LC-MS/MS) for topiramate analysis in human plasma has been applied to pharmacokinetic and bioequivalence studies in 24 healthy male Korean volunteers. The procedure involves a simple liquid extraction of topiramate and prednisone (internal standard) with acetonitrile and separation by HPLC equipped with a Capcell Pak C18 column using acetonitrile-0.1% triethylamine (80:20, v/v) as a mobile phase. Detection was carried out on an API 2000 MS system by multiple reactions monitoring mode. The ionization was optimized using ESI(-) and selectivity was achieved by MS/MS analysis, m/z 338.0 --> 77.5 and m/z 357.1 --> 327.2 for topiramate and prednisone, respectively. The method had a total run time of 2.5 min and showed good linearity over a working range of 20-5000 ng/mL in human plasma with a lower limit of quantification of 20 ng/mL. No metabolic compounds were found to interfere with the analysis. The inter-day and intra-day accuracy were in the ranges of 99.24-116.63 and 93.45-108.68%, respectively, and inter-day and intra-day precisions were below 6.24 and 5.25%, respectively. This method was successfully applied for pharmacokinetic and bioequivalence studies by analysis of blood samples taken up to 96 h after an oral administration of 100 mg of topiramate in 24 healthy Korean volunteers.

  5. A high-performance liquid chromatographic method for determination of scopolin in rat plasma: application to pharmacokinetic studies.

    Science.gov (United States)

    Xia, Yu-Feng; Dai, Yue; Wang, Qiang; Cai, Fei

    2008-10-01

    An analytical method based on high-performance liquid chromatographic (HPLC) with ultraviolet (UV) detection was developed for determination of scopolin in rat plasma using aesculin as internal standard (IS). After protein precipitation of plasma sample with methanol, the supernatant was directly injected and analyzed. Chromatographic separation was achieved on a C18 column using methanol and distilled water (22:78, v/v) containing 0.2% (v/v) glacial acetic acid as mobile phase with a column temperature of 30 degrees C. The UV detector was set at 338 nm. The calibration curve was linear over the range of 0.105-13.125 microg/mL with a correlation coefficient of 0.9998. The retention times of aesculin and scopolin were 10.4 and 12.8 min, respectively. The recoveries for plasma samples of 0.105, 4.725 and 13.125 microg/mL were 91.08, 95.30 and 96.10%, respectively. The RSD of intra- and inter-day assay variations was less than 7.35%. The lower limit of detection was 0.03 microg/mL .This HPLC assay is a simple, sensitive and accurate and was successfully applied to the pharmacokinetic study of scopolin in rats.

  6. Determination of scutellarin in plasma by solid phase extraction—high performance liquid chromatography and its pharmacokinetics

    Institute of Scientific and Technical Information of China (English)

    LiuYM; LiuAH

    2002-01-01

    Breviscapine has extensive effects and its main active component is scutellarin.This study established a solid phase extraction-high performance liquid chromatography (SPE-HPLC) method for determining scutellarin in plasma,and studied its pharmacokinetics after iv breviscapine in rabbits.Methanol-water-phosphoric acid was used as mobile phase,Nucleosil C18 column was welected.Plasma samples were pretreated by solid phase extraction.Fifteen rabbits(3 groups) were given breviscapine by iv at the dose of 10.0,20.0 and 40.0mg·kg-1,respectively.Scutellarin in plasma was determined.The linearity was obtained over the range of 0.02-10.0mg·L-1.The limit of detection was 0.02mg·L-1.After iv breviscapine in rabbits,the concentration-time curves of scutellarin was fitted to three compartment model.The results showed that this assay method was accurate,sensitive and simple.The changes of drug concentration in vivo exhibited linear kinetics over the dosage range of 10.0-20.0mg·kg-1,but when dosage was 40.0mg·kg-1,the linear kinetic properties did not exist.

  7. Determination of atractylon in rat plasma by a GC-MS method and its application to a pharmacokinetic study

    Institute of Scientific and Technical Information of China (English)

    Han Yan; Yuanyuan Sun; Yuying Ma; Bin Ji; Xiaohong Hou; Zhiguo Yu; Yunli Zhao

    2015-01-01

    A sensitive and selective method based on gas chromatography hyphenated to mass spectrometry (GC-MS) was developed and validated for the determination of atractylon in rat plasma. Plasma samples were processed by liquid-liquid extraction with ethyl acetate-n-hexane (1:1, v/v) using acetophenone as an internal standard (IS). Analytes were determined in selective ion monitoring (SIM) mode using target ions at m/z 108.1 for atractylon and m/z 105.1 for acetophenone. The calibration curve was linear over the concentration range of 10-1000 ng/mL with lower limit of quantification of 10 ng/mL. The intra- and inter-day precision variations were not more than 10.4% and 9.6%, respectively, whilst accuracy values ranged from -6.5% to 4.9%. Extraction recovery of the assay was satisfactory. This method was suc-cessfully applied to quantification and pharmacokinetic study of atractylon in rat plasma after in-tragastric administration of Atractylodis extract.

  8. Determination of atractylon in rat plasma by a GC–MS method and its application to a pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Han Yan

    2015-10-01

    Full Text Available A sensitive and selective method based on gas chromatography hyphenated to mass spectrometry (GC–MS was developed and validated for the determination of atractylon in rat plasma. Plasma samples were processed by liquid–liquid extraction with ethyl acetate-n-hexane (1:1, v/v using acetophenone as an internal standard (IS. Analytes were determined in selective ion monitoring (SIM mode using target ions at m/z 108.1 for atractylon and m/z 105.1 for acetophenone. The calibration curve was linear over the concentration range of 10–1000 ng/mL with lower limit of quantification of 10 ng/mL. The intra- and inter-day precision variations were not more than 10.4% and 9.6%, respectively, whilst accuracy values ranged from −6.5% to 4.9%. Extraction recovery of the assay was satisfactory. This method was successfully applied to quantification and pharmacokinetic study of atractylon in rat plasma after intragastric administration of Atractylodis extract.

  9. Quantification of mesembrine and mesembrenone in mouse plasma using UHPLC-QToF-MS: Application to a pharmacokinetic study.

    Science.gov (United States)

    Manda, Vamshi K; Avula, Bharathi; Ashfaq, Mohammad K; Abe, Naohito; Khan, Ikhlas A; Khan, Shabana I

    2017-03-01

    Sceletium tortuosum, is an indigenous herb of South Africa which is widely used as an herbal supplement in the treatment of anxiety and stress. Mesembrenone and mesembrine are the two main pharmacologically active alkaloids present in the extract. Despite the wide therapeutic applications of Sceletium extract, there are no reports of in vivo pharmacokinetic properties or analytical methods to quantify these two important alkaloids in plasma. Therefore, the current study aimed to develop and validate a simple and sensitive analytical method for simultaneous quantification of mesembrenone and mesembrine in mouse plasma. Ultra-high-performance liquid chromatography-mass spectrometry (UHPLC/QToF-MS) was employed to achieve our objectives. The compounds were extracted using protein precipitation by methanol (100%) with quinine as an internal standard. The lower limit of quantification for both the compounds was 10 ng/mL. The extraction recovery was between 87 and 93% for both compounds with no matrix effects on the analysis. The accuracy was between 89.5 and 106% and precision was alkaloids was poor and the plasma levels were below the detection limits.

  10. Determination of salvianolic acid C in rat plasma using liquid chromatography-mass spectrometry and its application to pharmacokinetic study.

    Science.gov (United States)

    Song, Junke; Zhang, Wen; Sun, Jialin; Zhang, Xue; Xu, Xiaona; Zhang, Li; Feng, Zhangying; Du, Guanhua

    2016-03-01

    A sensitive and reliable LC-ESI-MS method for the determination of salvianolic acid C in rat plasma has been developed and validated. Plasma samples were prepared by liquid-liquid extraction with ethyl acetate and separated on a Zorbax SB-C18 column (3.5 µm, 2.1 × 100 mm) at a flow rate of 0.3 mL/min using acetonitrile-water as mobile phase. The detection was carried out by a single quadrupole mass spectrometer with electrospray ionization source and selected ion monitoring mode. Linearity was obtained for salvianolic acid C ranging from 5 to 1000 ng/mL. The intra- and inter-day precisions (RSD, %) didn't exceed 9.96%, and the accuracy (RE, %) were all within ±3.64%. The average recoveries of the analyte and internal standard were >89.13%. Salvianolic acid C was proved to be stable during all sample storage, preparation and analytic procedures. The validated method was successfully applied to pharmacokinetic study after oral and intravenous administration of salvianolic acid C to rats. The absolute oral bioavailability of salvianolic acid C was 0.29 ± 0.05%. This method was further applied to simultaneous determination of salvianolic acid A, salvianolic acid B and salvianolic acid C in rat plasma and showed good practicability.

  11. Determination of pinocembrin in human plasma by solid-phase extraction and LC/MS/MS: application to pharmacokinetic studies.

    Science.gov (United States)

    Yan, Bei; Cao, Guoying; Sun, Taohua; Zhao, Xi; Hu, Xin; Yan, Jiling; Peng, Yueying; Shi, Aixin; Li, Yang; Xue, Wei; Li, Min; Li, Kexin; Liu, Yingfa

    2014-12-01

    A sensitive, fast and specific method for the quantitation of pinocembrin in human plasma based on high-performance liquid chromatography-tandem mass spectrometry (LC/MS/MS) was developed and validated. Clonazepam was used as the internal standard (IS). After solid-phase extraction of 500 μL plasma, pinocembrin and the IS were separated on a Luna C8 column using the mobile phase composed of acetonitrile-0.3 mm ammonium acetate solution (65:35, v/v) at a flow rate of 0.25 mL/min in isocratic mode. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring via an electrospray ionization source in negative mode by AB SCIEX Qtrap 5500. The assay was linear from 1 to 400 ng/mL, with within- and between-run accuracy (relative error) from -1.82 to 0.54%, and within- and between-run precision (CV) below 5.25%. The recovery was above 88% for the analyte at 1, 50 and 300 ng/mL. This analytical method was successful for the determination of pinocembrin in human plasma and applied to a pharmacokinetic study of pinocembrin injection in healthy volunteers after intravenous drip administration. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Determination of fenticonazole in human plasma by HPLC–MS/MS and its application to pharmacokinetic studies

    Directory of Open Access Journals (Sweden)

    Weixing Mao

    2017-02-01

    Full Text Available Two simple and sensitive high performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS methods were developed and validated for the determination of fenticonazole in human plasma after percutaneous and intravaginal administration. Mifepristone was used as an internal standard (IS, and simple protein precipitation by acetonitrile containing 2% acetic acid was utilized for extracting the analytes from the plasma samples. Chromatographic separation was performed on a Kinetex XB-C18 column. The quantitation was performed by a mass spectrometer equipped with an electrospray ionization source in multiple reactions monitoring (MRM positive ion mode using precursor-to-product ion transitions of m/z 455.2–199.1 for fenticonazole and m/z 430.2–372.3 for mifepristone. The validated linear ranges were 5–1000 pg/mL and 0.1–20 ng/mL fenticonazole in plasma for the methods A and B, respectively. For the two methods, the accuracy data ranged from 85% to 115%, the intra- and inter-batch precision data were less than 15%, the recovery data were more than 90%, and no matrix interference was observed. The methods A and B were successfully validated and applied to the pharmacokinetic studies of fenticonazole gel in Chinese healthy volunteers after percutaneous and intravaginal administration, respectively.

  13. Simulation of Human Plasma Concentrations of Thalidomide and Primary 5-Hydroxylated Metabolites Explored with Pharmacokinetic Data in Humanized TK-NOG Mice.

    Science.gov (United States)

    Nishiyama, Sayako; Suemizu, Hiroshi; Shibata, Norio; Guengerich, F Peter; Yamazaki, Hiroshi

    2015-11-16

    Plasma concentrations of thalidomide and primary 5-hydroxylated metabolites including 5,6-dihydroxythalidomide and glutathione (GSH) conjugate(s) were investigated in chimeric mice with highly "humanized" liver cells harboring cytochrome P450 3A5*1. Following oral administration of thalidomide (100 mg/kg), plasma concentrations of GSH conjugate(s) of 5-hydroxythalidomide were higher in humanized mice than in controls. Simulation of human plasma concentrations of thalidomide were achieved with a simplified physiologically based pharmacokinetic model in accordance with reported thalidomide concentrations. The results indicate that the pharmacokinetics in humans of GSH conjugate and/or catechol primary 5-hydroxylated thalidomide contributing in vivo activation can be estimated for the first time.

  14. UPLC-MS/MS determination of ephedrine, methylephedrine, amygdalin and glycyrrhizic acid in Beagle plasma and its application to a pharmacokinetic study after oral administration of Ma Huang Tang.

    Science.gov (United States)

    Yan, Tianhua; Fu, Qiang; Wang, Jing; Ma, Shiping

    2015-02-01

    An ultra performance liquid chromatography-mass spectrometric (UPLC-MS) method was developed to investigate the pharmacokinetic properties of ephedrine, methylephedrine, amygdalin, and glycyrrhizic acid after oral gavage of Ma Huang Tang (MHT) in Beagles. Beagle plasma samples were pretreated using liquid-liquid extraction, and chromatographic separation was performed on a C18 column using a linear gradient of water-formic acid mixture (0.1%). The pharmacokinetic parameters of ephedrine, methylephedrine, amygdalin, and glycyrrhizic acid from MHT in Beagles were quantitatively determined by UPLC with tandem mass detector. The qualitative detection of the four compounds was accomplished by selected ion monitoring in negative/positive ion modes electrospray ionization-mass spectrometry (ESI-MS). Detection was based on multiple reaction monitoring with the precursor-to-product ion transitions m/z 166.096-116.983 (ephedrine), m/z 179.034-146.087 (methylephedrine), m/z 456.351-323.074 (amygdalin), and m/z 821.606-351.062 (glycyrrhizic acid). The selectivity, sensitivity, linearity, accuracy, precision, extraction recovery, ion suppression, and stability were within the acceptable ranges. The method described was successfully applied to reveal the pharmacokinetic properties of ephedrine, methylephedrine, amygdalin, and glycyrrhizic acid after oral gavage of MHT in Beagles. Copyright © 2014 John Wiley & Sons, Ltd.

  15. The effect of thermophoresis on the discharge parameters in complex plasma experiments

    CERN Document Server

    Land, Victor; Creel, James; Schmoke, Jimmy; Cook, Mike; Matthews, Lorin; Hyde, Truell

    2010-01-01

    Thermophoresis is a tool often applied in complex plasma experiments. One of the usual stated benefits over other experimental tools is that changes induced by thermophoresis neither directly depend on, nor directly influence, the plasma parameters. From electronic data, plasma emission profiles in the sheath, and Langmuir probe data in the plasma bulk, we conclude that this assumption does not hold. An important effect on the levitation of dust particles in argon plasma is observed as well. The reason behind the changes in plasma parameters seems to be the change in neutral atom density accompanying the increased gas temperature while running at constant pressure.

  16. The effect of electrode heating on the discharge parameters in complex plasma experiments

    Energy Technology Data Exchange (ETDEWEB)

    Land, Victor; Carmona-Reyes, Jorge; Creel, James; Schmoke, Jimmy; Cook, Mike; Matthews, Lorin; Hyde, Truell, E-mail: victor_land@baylor.edu [Center for Astrophysics, Space Physics, and Engineering Research, Baylor University, Waco, TX, 76798-7316 (United States)

    2011-02-15

    Thermophoresis is a tool often applied in complex plasma experiments. One of the usual stated benefits over other experimental tools is that electrode temperature changes required to induce thermophoresis do not directly influence the plasma parameters. From electronic data, plasma emission profiles in the sheath, and Langmuir probe data in the plasma bulk, we conclude that this assumption does not hold. An important effect on the levitation of dust particles in argon plasma is observed as well. The reason behind the changes in plasma parameters seems to be the change in neutral atom density accompanying the increased gas temperature while running at constant pressure.

  17. Nonlinear Optical Parameters of Magnetoactive Semiconductor-Plasmas

    Science.gov (United States)

    Singh, M.; Joseph, D.; Duhan, S.

    The nonlinear optical parameters (absorption coefficient and refractive index) of semiconductor-plasmas subjected to a transverse magnetic field have been investigated analytically. By employing the coupled-mode scheme, an expression of third-order optical susceptibility and resultant nonlinear absorption and refractive index of the medium are obtained. The analysis has been applied to both cases, viz., centrosymmetric (β = 0) and noncentrosymmetric (β ≠ 0) in the presence of magnetic field. The numerical estimates are made for InSb crystal at liquid nitrogen temperature duly irradiated by a 10-nanosecond pulsed 10.6 μm CO2 laser. The influence of doping concentration and magnetic field on both the nonlinear absorption and refractive index has been explored, and the results are found to be well in agreement with theory and experiment. Analysis further establishes that absorption coefficient and refractive index can be controlled with precision in semiconductors by the proper selection of doping concentration and an external magnetic field, and hence these media may be used for fabrication of fast cubic nonlinear optical devices under off-resonant transition regime.

  18. Transplacental pharmacokinetics of cocaine and benzoylecgonine in plasma and hair of rhesus monkeys.

    Science.gov (United States)

    Bailey, B; Morris, P; McMartin, K I; Klein, J; Duhart, H M; Gillam, M P; Binienda, Z; Slikker, W; Paule, M G; Koren, G

    1998-01-01

    There is large variability in the rate and extent of fetal damage from cocaine in humans; however, the sources of such variability are not presently known. In order to study the relationship between maternal cocaine pharmacokinetics at the end of pregnancy and maternal or infant cocaine and benzoylecgonine hair concentrations at birth, ten rhesus monkeys were administered cocaine intramuscularly throughout pregnancy. Cocaine and benzoylecgonine hair concentrations were determined at birth and correlated with maternal pharmacokinetics during pregnancy. There were no correlations between either maternal cocaine Cmax or AUC0-infinity and maternal and infant hair cocaine or benzoylecgonine concentrations. There were no significant correlations between maternal hair benzoylecgonine concentrations and either maternal benzoylecgonine AUC0-120 (r = 0.60; P = 0.07) or benzoylecgonine Cmax (r = 0.60; P = 0.07). No correlations existed between infant hair benzoylecgonine concentrations and either maternal benzoylecgonine AUC0-120 (r = 0.30; P = 0.40) or benzoylecgonine Cmax (r = 0.30; P = 0.40). Also, no correlation was found between maternal cocaine dose and maternal or infant cocaine and benzoylecgonine hair concentrations. In comparison to toxicants such as nicotine and carbon monoxide for which there is a good correlation between maternal systemic exposure and neonatal concentrations, the lack of a similar relationship for cocaine is consistent with the role of the placenta in contributing to the variability in the amounts of cocaine reaching the fetus and hence, potentially to the risk of adverse fetal outcome.

  19. Determination and validation of chikusetsusaponin IVa in rat plasma by UPLC-MS/MS and its application to pharmacokinetic study.

    Science.gov (United States)

    Wang, Ying; Liu, Shi-Ping; Guo, Mei-Hua; Wang, Zhuo

    2016-09-01

    A novel, sensitive and rapid ultra-performance liquid chromatography-tandem mass spectrometric method for the quantification of chikusetsusaponin IVa (CHS-IVa) in rat plasma was established and validated. Plasma samples were pre-treated by precipitation of protein with acetonitrile and chromatographed on a Waters Symmetry C18 analytical column (4.6 × 50 mm, i.d., 3.5 μm) using a mobile phase consisting of methanol and water containing 0.05% formic acid (55:45, v/v) at a flow rate of 0.4 mL/min. The deprotonated molecular ions [M - H](-) were employed in electrospray negative ionization mode and selected reaction monitoring transitions were performed for detection. The calibration curves exhibited good linearity (r > 0.99) over the range of 0.5-1000 ng/mL for CHS-IVa. The recoveries of CHS-IVa were >92.5% and exhibited no severe matrix effect. This method was successfully applied in the pharmacokinetic study of CHS-IVa in rats. For oral administration, the plasma concentrations of CHS-IVa increased to a peak value at 0.35 ± 0.14 h, followed by a gradual decrease to the lower limit of quantitation in 24 h. For intravenous administration, the plasma concentrations of CHS-IVa decreased quickly (t1/2 , 1.59 ± 0.25 h). The absolute bioavailability of CHS-IVa in rats was 8.63%. Copyright © 2016 John Wiley & Sons, Ltd.

  20. Determination of the unstable drug otilonium bromide in human plasma by LC-ESI-MS and its application to a pharmacokinetic study.

    Science.gov (United States)

    Zhao, Yan-Rong; Ding, Li; Fan, Hong-Wei; Yu, Yong; Qi, Xie-Min; Leng, Ye; Rao, Ya-Kun

    2010-10-15

    Otilonium bromide (OB) degrades rapidly in plasma and readily undergoes hydrolysis by the plasma esterase. In this paper, an LC-ESI-MS method has been developed for the determination of OB in human plasma. The rapid degradation of OB in plasma was well prevented by immediate addition of potassium fluoride (KF, an inhibitor of plasma esterase) to the freshly collected plasma before prompt treatment with acetonitrile. The method was validated over the concentration range of 0.1-20ng/ml. The data of intra-run and inter-run precision and accuracy were within ±15%. The mean extraction recoveries for OB and the internal standard were higher than 93.0% and the matrix effects were negligible. The method has been successfully used in a pharmacokinetic study. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Pharmacokinetics of Moxifloxacin in Cerebrospinal Fluid and Plasma in Patients with Tuberculous Meningitis

    NARCIS (Netherlands)

    Alffenaar, J. W. C.; van Altena, R.; Bokkerink, H. J.; Luijckx, G. J.; van Soolingen, D.; Aarnoutse, R. E.; van der Werf, T. S.

    2009-01-01

    Moxifloxacin cerebrospinal fluid (CSF) penetration was evaluated by obtaining full plasma and CSF time concentration curves for 4 patients with tuberculous meningitis. The geometric mean ratio of the areas under the curve for CSF to plasma were 0.82 (range, 0.70-0.94) at 400 mg once per day and 0.71

  2. Spectroscopic studies of the parameters of plasma jets during their propagation in the background plasma on the PF-3 facility

    Science.gov (United States)

    Dan’ko, S. A.; Ananyev, S. S.; Kalinin, Yu G.; Krauz, V. I.; Myalton, V. V.

    2017-04-01

    This paper presents measurement results of neon and helium plasma parameters in axial jets generated in plasma focus discharge. They were obtained in the course of experiments on laboratory modeling of astrophysical jets performed at the PF-3 facility. The plasma concentration was determined according to Stark broadening of spectral lines; the ionization temperature was determined by the average ion charge. The values of the concentration and temperature of jet plasma and background plasma at two distances from the pinch are also presented. In addition, an estimation was made of the heat content losses of the neon and helium jets during their movement through the surrounding medium.

  3. Simultaneous determination of mangiferin and neomangiferin in rat plasma by UPLC-MS/MS and its application for pharmacokinetic study.

    Science.gov (United States)

    Qiu, Xiangjun; Zhao, Jian-long; Hao, Cong; Yuan, Canli; Tian, Nuan; Xu, Zhi-sheng; Zou, Ruan-min

    2016-05-30

    In this study, a sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed to determine mangiferin and neomangiferin in rat plasma simultaneously. Chromatographic separation was carried out on an Acquity UPLC BEH C18 column and mass spectrometric analysis was performed using a Xevo TQD triple quadruple mass spectrometer coupled with an electrospray ionization (ESI) source. The MRM transitions of m/z 423.2 → 303.1 and m/z 585.0 → 273.1 were used to quantify for mangiferin and neomangiferin, respectively. The linearity of this method was found to be within the concentration range of 5-2000 ng/mL for mangiferin, and 2-1000 ng/mL for neomangiferin in rat plasma, respectively. Only 3.0 min was needed for an analytical run. This assay was used to support a preclinical study to investigate the pharmacokinetics of mangiferin and neomangiferin in rats.

  4. Simultaneous quantification of picfeltarraenins IA and IB in rat plasma by UPLC-MS/MS: Application to a pharmacokinetic study.

    Science.gov (United States)

    He, Xin; Zhang, Yingjie; Gao, Hang; Li, Keyan; Zhang, Yazhuo; Sun, Limin; Tao, Guizhou

    2016-02-20

    A simple and rapid quantitative UPLC-MS/MS method for simultaneous determination of picfeltarraenins IA and IB in rat plasma was developed and validated in accordance with the US FDA Bioanalytical Guidance (2001). Analytes were extracted from rat plasma by using methanol and separated on Agilent ZORBAX SB-C18 (50mm×2.1mm, 1.8μm) column by using a mobile phase composed of methanol and water (70:30, v/v). Eluents were monitored by ESI tandem mass spectrometry detection with SRM mode using ion transitions m/z 785.4→639.5, m/z 815.5→669.5, and m/z 763.5→455.3 for picfeltarraenin IA, picfeltarraenin IB, and internal standard, respectively. The method was validated over the linear range of 11.5-1150ng/mL and 13.0-1300ng/mL. The developed analytical method was applied to support a pharmacokinetic study on simultaneous estimation of picfeltarraenins IA and IB in rats.

  5. Micellar electrokinetic chromatographic determination of rosuvastatin in rabbit plasma and evaluation of its pharmacokinetics and interaction with niacin.

    Science.gov (United States)

    El-Kommos, Michael E; Mohamed, Niveen A; Ali, Hassan R H; Abdel Hakiem, Ahmed F

    2014-12-01

    A specific, accurate, precise and reproducible micellar electrokinetic chromatographic method was developed for in vitro and in vivo estimation of rosuvastatin, a synthetic and potent HMG-CoA inhibitor, in rabbit plasma. Further, its pharmacokinetics in the presence of niacin, which could be co-administered for monitoring of severe hypercholestremia, was investigated. The assay procedures involved simple liquid-liquid extraction of rosuvastatin and internal standard, atorvastatin, from a small plasma volume directly into acetonitrile. The organic layer was separated and evaporated under a gentle stream of nitrogen. The residue was reconstituted in the mobile phase and injected electrokinetically into electropherosis system. The background electrolyte consisted of borate buffer (25.0 mm, pH 9.5), 10.0% organic modifier (5.0% methanol + 5.0% acetonitrile) and 25.0 mm sodium dodecyl sulfate at 20.0 kV applied voltage and 215.0 nm detection wavelength for the effective separation of rosuvastatin, niacin and atorvastatin.

  6. Determination of rutin in rat plasma by ultra performance liquid chromatography tandem mass spectrometry and application to pharmacokinetic study.

    Science.gov (United States)

    Chen, Mengchun; Zhang, Xiaoqian; Wang, Hao; Lin, Baoli; Wang, Shuanghu; Hu, Guoxin

    2015-04-01

    A sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS-MS) method for the determination of rutin in rat plasma was developed and validated. After addition of tolbutamide as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. The chromatographic separation was performed on an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 μm particle size), using acetonitrile-0.1% formic acid as the mobile phase with gradient elution, delivered at a flow-rate of 0.4 mL/min. Mass spectrometric analysis was performed using a XEVO TQD mass spectrometer coupled with an electro-spray ionization (ESI) source in the positive ion mode. The MRM transitions of m/z 610.91→302.98 and m/z 271.2→155.1 were used to quantify for rutin and tolbutamide, respectively. This assay method has been fully validated in terms of specificity, linearity, recovery and matrix effect, accuracy, precision and stability. Calibration curves were linear in the concentration ranges of 25-2000 ng/mL for rutin. Only 3 min was needed for an analytical run. This developed method was successfully used for determination of rutin in rat plasma for pharmacokinetic study.

  7. Determination of roxatidine in human plasma by liquid chromatography/electrospray mass spectrometry and application to a clinical pharmacokinetic study.

    Science.gov (United States)

    Shin, Beom Soo; Choi, Jin Won; Balthasar, Joseph P; Hong, Deok Ki; Kim, Jung Jun; Yoo, Sun Dong

    2007-01-01

    A rapid and sensitive liquid chromatography/mass spectrometry (LC/MS) method was developed and validated for the determination of roxatidine in human plasma. Roxatidine was extracted by single liquid-liquid extraction with tert-butyl methyl ether, and the chromatographic separation was performed on a C8 column. The total analytical run time was relatively short (5 min), and the limit of assay quantification was 2 ng/mL using 0.1 mL of human plasma. Roxatidine and the internal standard, propranolol, were monitored in selected ion monitoring (SIM) mode at m/z 307.3 and 260.3, respectively. The standard curve was linear over a concentration range from 2-500 ng/mL, and the correlation coefficients were >0.999. The mean intra- and inter-day assay accuracy ranged from 103.4-108.8% and 102.3-110.0%, respectively, and the mean intra- and inter-day precision was between 3.3-8.8% and 5.3-6.2%, respectively. The developed assay method was successfully applied to a pharmacokinetic study in human volunteers after oral administration of roxatidine acetate hydrochloride at a dose of 75 mg.

  8. Determination of rizatriptan in human plasma by liquid chromatographic-eletrospray tandem mass spectrometry: application to a pharmacokinetic study.

    Science.gov (United States)

    Guo, Ji-fen; Zhang, Ai-jun; Zhao, Ling; Sun, Xiao-hong; Zhao, Yi-min; Gao, Hong-zhi; Liu, Ze-yuan; Qiao, Shan-yi

    2006-01-01

    A sensitive liquid chromatographic-tandem mass spectrometry(LC-MS/MS) method was developed for the determination of rizatriptan in human plasma. The analytes were extracted from plasma samples by liquid-liquid extraction, separated on a Zorbax XDB C8 column (150 x 4.6 mm i.d.) and detected by tandem mass spectrometry with an electrospray ionization interface. Zomitriptan was used as the internal standard. The method had a lower limit of quantitation of 50 pg/mL for rizatriptan, which showed more sensitivity and speed of analysis compared with reported methods. The within- and between-day precision was measured to be below 11.71% and accuracy between -5.87 and 0.86% for all quality control samples. This quantitation method was successfully applied to the evaluation of the pharmacokinetic profiles of rizatriptan after single oral administration of 5, 10 and 15 mg rizatriptan tablets to 10 healthy volunteers (five males and five females).

  9. Development of a LC-MS/MS method for the determination of CKD-712 in rat plasma: Application to a pharmacokinetic study in rats.

    Science.gov (United States)

    Chae, Jung-Woo; Yun, Hwi-Yeol; Eom, Han Young; Jeong, Eun Ju; Koo, Tae-Sung; Kwon, Kwang-Il; Lee, Jong-Hwa

    2017-09-01

    CKD-712 is a potential treatment for sepsis, as it exhibits protective effects against lipopolysaccharide-mediated platelet aggregation, inducible nitric oxide synthase expression, and cecum-ligation puncture-induced septic mortality in mice. In this study, we develop a rapid and sensitive LC-MS/MS method for determining CKD-712 in rat plasma. CKD-712 and papaverine hydrochloride (an internal standard) were analyzed using an LC-MS/MS system consisting of an Agilent HPLC system (HP-1100) equipped with an Atlantis HILIC Silica (2.1×50mm, 3μm) column and a API 4000 (Applied Biosystems/MDS Sciex, USA) in a positive ESI mode. We utilized multiple reaction monitoring (MRM) at m/z transitions of 306.2-164.0 to analyze CKD-712, and 340.3-202.1 m/z for IS, with a mobile phase of acetonitrile (0.025% trifluoroacetic acid):20mM ammonium acetate (94:6, v/v) at a flow rate of 0.25mL/min. The lower limit of quantification (LLOQ) was 5ng/mL, with a linearity ranging from 5 to 1000ng/mL (r>0.999). Validation parameters including specificity, precision, accuracy, matrix effect, recovery, dilution effect and stability results were well within acceptance criteria, and applied successfully on a pharmacokinetic study in rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Determination of treosulfan in plasma and urine by HPLC with refractometric detection; pharmacokinetic studies in children undergoing myeloablative treatment prior to haematopoietic stem cell transplantation.

    Science.gov (United States)

    Główka, Franciszek K; Łada, Marta Karaźniewicz; Grund, Grzegorz; Wachowiak, Jacek

    2007-05-01

    A direct and selective HPLC method with refractometric detection was worked out for determination of treosulfan in plasma and urine of children. Before injection onto reverse phase column plasma samples with treosulfan and barbital (I.S.) were clarified using filtration. The mobile phase was composed of phosphate buffer, pH 5 and acetonitrile. The linear range of the standard curve of treosulfan spanned concentrations of 10.0-2000.0 microg/ml and 50.0-10000.0 microg/ml in plasma and urine, respectively, and covered the levels found in biological fluids after infusion of the drug. The limit of detection amounted to 5 microg/ml for plasma and 25 microg/ml for urine. Intra- and inter-day precision and accuracy of the measurement fulfilled analytical criteria accepted in pharmacokinetic studies. Recovery of treosulfan as well as stability in biological fluids was also calculated. The validated method was successfully applied in pharmacokinetic studies of treosulfan administered to children prior to haematopoietic stem cell transplantation. Differences between pharmacokinetics of treosulfan in children and adults were also studied.

  11. Pharmacokinetics of repeated sodium salicylate administration to laying hens: evidence for time dependent increase in drug elimination from plasma and eggs.

    Directory of Open Access Journals (Sweden)

    Błażej Poźniak

    Full Text Available Salicylates were the first non-steroid anti-inflammatory drugs (NSAIDs to be used in any species and are still widely used in humans and livestock. However, the data on their pharmacokinetics in animals is limited, especially after repeated administration. Evidence exist that in chickens (Gallus gallus salicylate (SA may induce its own elimination. The aim of this study was to investigate salicylate pharmacokinetics and egg residues during repeated administration of sodium salicylate (SS to laying hens. Pharmacokinetics of SA was assessed during 14 d oral administration of SS at daily doses of 50 mg/kg and 200 mg/kg body weight to laying hens. On the 1st, 7th and 14th d a 24 h-long pharmacokinetic study was carried out, whereas eggs were collected daily. Salicylate concentrations in plasma and eggs were determined using high-performance liquid chromatography with ultraviolet detection and pharmacokinetic variables were calculated using a non-compartmental model. Mean residence time (MRT, minimal plasma concentration (Cmin, C16h and elimination half-life (T1/2el of SA showed gradual decrease in layers administered with a lower dose. Total body clearance (ClB increased. Layers administered with the higher dose showed a decrease only in the T1/2el. In the low dose group, SA was found only in the egg white and was low throughout the experiment. Egg whites from the higher dose group showed initially high SA levels which significantly decreased during the experiment. Yolk SA levels were lower and showed longer periods of accumulation and elimination. Repeated administration of SS induces SA elimination, although this effect may differ depending on the dose and production type of a chicken. Decreased plasma drug concentration may have clinical implications during prolonged SS treatment.

  12. Parameters influencing plasma column potential in a reflex discharge

    Science.gov (United States)

    Liziakin, G. D.; Gavrikov, A. V.; Murzaev, Y. A.; Usmanov, R. A.; Smirnov, V. P.

    2016-12-01

    Distribution of electrostatic potential in direct current reflex discharge plasma has been studied experimentally. Measurements have been conducted by the single floating probe method. The influence of 0-0.2 T magnetic field, 1-200 mTorr pressure, 0-2 kV discharge voltage, and electrodes geometry on plasma column electrostatic potential was investigated. The possibility for the formation of a preset potential profile required for the realization of plasma separation of spent nuclear fuel was demonstrated.

  13. Effects of amodiaquine and artesunate on sulphadoxine-pyrimethamine pharmacokinetic parameters in children under five in Mali

    Directory of Open Access Journals (Sweden)

    Doumbo Ogobara K

    2011-09-01

    Full Text Available Abstract Background Sulphadoxine-pyrimethamine, in combination with artesunate or amodiaquine, is recommended for the treatment of uncomplicated malaria and is being evaluated for intermittent preventive treatment. Yet, limited data is available on pharmacokinetic interactions between these drugs. Methods In a randomized controlled trial, children aged 6-59 months with uncomplicated falciparum malaria, received either one dose of sulphadoxine-pyrimethamine alone (SP, one dose of SP plus three daily doses of amodiaquine (SP+AQ or one dose of SP plus 3 daily doses of artesunate (SP+AS. Exactly 100 μl of capillary blood was collected onto filter paper before drug administration at day 0 and at days 1, 3, 7, 14, 21 and 28 after drug administration for analysis of sulphadoxine and pyrimethamine pharmacokinetic parameters. Results Fourty, 38 and 31 patients in the SP, SP+AQ and SP+AS arms, respectively were included in this study. The concentrations on day 7 (that are associated with therapeutic efficacy were similar between the SP, SP+AQ and SP+AS treatment arms for sulphadoxine (median [IQR] 35.25 [27.38-41.70], 34.95 [28.60-40.85] and 33.40 [24.63-44.05] μg/mL and for pyrimethamine (56.75 [46.40-92.95], 58.75 [43.60-98.60] and 59.60 [42.45-86.63] ng/mL. There were statistically significant differences between the pyrimethamine volumes of distribution (4.65 [3.93-6.40], 4.00 [3.03-5.43] and 5.60 [4.40-7.20] L/kg; p = 0.001 and thus elimination half-life (3.26 [2.74 -3.82], 2.78 [2.24-3.65] and 4.02 [3.05-4.85] days; p . This study confirmed the lower SP concentrations previously reported for young children when compared with adult malaria patients. Conclusion Despite slight differences in pyrimethamine volumes of distribution and elimination half-life, these data show similar exposure to SP over the critical initial seven days of treatment and support the current use of SP in combination with either AQ or AS for uncomplicated falciparum malaria

  14. Pharmacokinetic study of arctigenin in rat plasma and organ tissue by RP-HPLC method.

    Science.gov (United States)

    He, Fan; Dou, De-Qiang; Hou, Qiang; Sun, Yu; Kang, Ting-Guo

    2013-01-01

    A high-performance liquid chromatography (HPLC) technique was developed for the determination of arctigenin in plasma and various organs of rats after the oral administration of 30, 50 and 70 mgkg(-1) of arctigenin to the Sprague-Dawley rats. Results showed that the validated HPLC method was simple, fast, reproducible and suitable to the determination of arctigenin in rat plasma and organ tissue and one-compartmental model with zero-order absorption process can well describe the changes of arctigenin concentration in the plasma. The concentration of compound was highest in the spleen, less in the liver and the least in the lung.

  15. Limited-sampling strategy models for estimating the pharmacokinetic parameters of 4-methylaminoantipyrine, an active metabolite of dipyrone

    Directory of Open Access Journals (Sweden)

    Suarez-Kurtz G.

    2001-01-01

    Full Text Available Bioanalytical data from a bioequivalence study were used to develop limited-sampling strategy (LSS models for estimating the area under the plasma concentration versus time curve (AUC and the peak plasma concentration (Cmax of 4-methylaminoantipyrine (MAA, an active metabolite of dipyrone. Twelve healthy adult male volunteers received single 600 mg oral doses of dipyrone in two formulations at a 7-day interval in a randomized, crossover protocol. Plasma concentrations of MAA (N = 336, measured by HPLC, were used to develop LSS models. Linear regression analysis and a "jack-knife" validation procedure revealed that the AUC0-¥ and the Cmax of MAA can be accurately predicted (R²>0.95, bias 0.85 of the AUC0-¥ or Cmax for the other formulation. LSS models based on three sampling points (1.5, 4 and 24 h, but using different coefficients for AUC0-¥ and Cmax, predicted the individual values of both parameters for the enrolled volunteers (R²>0.88, bias = -0.65 and -0.37%, precision = 4.3 and 7.4% as well as for plasma concentration data sets generated by simulation (R²>0.88, bias = -1.9 and 8.5%, precision = 5.2 and 8.7%. Bioequivalence assessment of the dipyrone formulations based on the 90% confidence interval of log-transformed AUC0-¥ and Cmax provided similar results when either the best-estimated or the LSS-derived metrics were used.

  16. Limited-sampling strategy models for estimating the pharmacokinetic parameters of 4-methylaminoantipyrine, an active metabolite of dipyrone.

    Science.gov (United States)

    Suarez-Kurtz, G; Ribeiro, F M; Estrela, R C; Vicente, F L; Struchiner, C J

    2001-11-01

    Bioanalytical data from a bioequivalence study were used to develop limited-sampling strategy (LSS) models for estimating the area under the plasma concentration versus time curve (AUC) and the peak plasma concentration (Cmax) of 4-methylaminoantipyrine (MAA), an active metabolite of dipyrone. Twelve healthy adult male volunteers received single 600 mg oral doses of dipyrone in two formulations at a 7-day interval in a randomized, crossover protocol. Plasma concentrations of MAA (N = 336), measured by HPLC, were used to develop LSS models. Linear regression analysis and a "jack-knife" validation procedure revealed that the AUC(0-infinity) and the Cmax of MAA can be accurately predicted (R2>0.95, bias 0.85) of the AUC(0-infinity) or Cmax for the other formulation. LSS models based on three sampling points (1.5, 4 and 24 h), but using different coefficients for AUC(0-infinity) and Cmax, predicted the individual values of both parameters for the enrolled volunteers (R2>0.88, bias = -0.65 and -0.37%, precision = 4.3 and 7.4%) as well as for plasma concentration data sets generated by simulation (R2>0.88, bias = -1.9 and 8.5%, precision = 5.2 and 8.7%). Bioequivalence assessment of the dipyrone formulations based on the 90% confidence interval of log-transformed AUC(0-infinity) and Cmax provided similar results when either the best-estimated or the LSS-derived metrics were used.

  17. Simultaneous determination of gastrodin and puerarin in rat plasma by HPLC and the application to their interaction on pharmacokinetics.

    Science.gov (United States)

    Jiang, Li; Dai, Jundong; Huang, Zhenlin; Du, Qinghua; Lin, Jiahao; Wang, Yurong

    2013-02-01

    Gastrodin (Gas) and puerarin (Pur) are bioactive substances derived from traditional Chinese medicine Gastrodia elata and Radix Puerariae, respectively, which were often used together in Chinese clinical prescriptions. Their injections were used in combined way for treatment of some cardiocerebrovascular diseases in clinic, especially for vertigo due to vertebrobasilar ischemia. In this paper, interaction of gastrodin and puerarin in rat plasma pharmacokinetics via intragastic (i.g.)/intravenous (i.v.) administration was investigated. A reliable HPLC method was developed for simultaneous determination of Gas and Pur in rat plasma with a linear range of 0.101-101 μg/mL for Gas and 0.0500-5.98 μg/mL for Pur (r(2)>0.993). The LLOQ, LOD of Gas and Pur were determined to be 0.101, 0.0486 μg/mL, and 0.05, 0.0245 μg/mL, respectively. The intra-day and inter-day precision were all less than 12.0%, whilst the accuracy were all within 96.4±6.00%. The proposed method has been successfully applied to the pharmacokinetic study of the analytes in rats after i.g./i.v. administration of Gas and Pur alone or combined with each other (i.g.: 40 mg/kg Gas, 400 mg/kg Pur; i.v.: 20 mg/kg Gas, 20 mg/kg Pur). Blood samples were collected from retinal vein plexus of rats at predetermined time points and plasma containing the internal standard tyrosol (IS) were precipitated by methanol and chromatography was carried out on a C(18) column with a gradient mobile phase of ACN-H(2)O with 0.05% phosphoric acid as a modifier. The pharmacokinetic profiles of combined administration were found to be distinct from those of given alone. The C(max), T(max), T(1/2), MRT of Gas administrated alone or combined with Pur via i.g. were 21.7 μg/mL, 0.250 h, 2.81 h, 0.830 h and 18.4 μg/mL, 0.550 h, 0.970 h, 1.37 h, respectively, of Pur administrated alone or combined with Gas via i.g. were 0.490 μg/mL, 1.95 h, 1.33 h, 2.10 h and 2.01 μg/mL, 0.570 h, 4.00 h, 5.10 h, respectively. The relative oral

  18. Simultaneous Quantification of Baricitinib and Methotrexate in Rat Plasma by LC-MS/MS: Application to a Pharmacokinetic Study.

    Science.gov (United States)

    Veeraraghavan, Sridhar; Thappali, Satheeshmanikandan R S; Viswanadha, Srikant; Vakkalanka, Swaroop; Rangaswamy, Manivannan

    2016-01-01

    Efficacy assessments using a combination of baricitinib and methotrexate necessitate the development of an analytical method for the determination of both drugs in plasma with precision. A high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of baricitinib and methotrexate in rat plasma. Extraction of baricitinib, methotrexate, and tolbutamide (internal standard; IS) from 50 µL of rat plasma was carried out by protein precipitation with methanol. Chromatographic separation of the analytes was performed on the YMC pack ODS AM (150 mm × 4.6 mm, 5 µm) column under gradient conditions with methanol: 2.0 mM ammonium acetate buffer as the mobile phases at a flow rate of 1 mL/min. The precursor ion and product ion transition for both analytes and IS were monitored on a triple quadrupole mass spectrometer, operated with selective reaction monitoring in positive ionization mode. The method was validated over a concentration range of 0.5-250.00 ng/mL for baricitinib and methotrexate. Mean extraction recoveries for baricitinib, methotrexate, and IS of 86.8%, 89.4%, and 91.8% were consistent across low, medium, and high QC levels, respectively. Precision and accuracy at low, medium, and high quality control levels were less than 15% across the analytes. Benchtop, wet, freeze-thaw, and long-term stability were evaluated for both of the analytes. The analytical method was applied to support the pharmacokinetic study of simultaneous estimation of baricitinib and methotrexate in Wistar rats. Assay reproducibility was demonstrated by reanalysis of 18 incurred samples.

  19. Comparative pharmacokinetics of tetramethylpyrazine phosphate in rat plasma and extracellular fluid of brain after intranasal, intragastric and intravenous administration

    Directory of Open Access Journals (Sweden)

    Dongmei Meng

    2014-02-01

    Full Text Available The purpose of this study was to compare the pharmacokinetic profiles of tetramethylpyrazine phosphate (TMPP in plasma and extracellular fluid of the cerebral cortex of rats via three delivery routes: intranasal (i.n., intragastric (i.g. and intravenous (i.v. administration. After i.n., i.g. and i.v. administration of a single-dose at 10 mg/kg, cerebral cortex dialysates and plasma samples drawn from the carotid artery were collected at timed intervals. The concentration of TMPP in the samples was analyzed by HPLC. The area under the concentration–time curve (AUC and the ratio of the AUCbrain to the AUCplasma (drug targeting efficiency, DTE was calculated to evaluate the brain targeting efficiency of the drug via these different routes of administration. After i.n. administration, TMPP was rapidly absorbed to reach its peak plasma concentration within 5 min and showed a delayed uptake into cerebral cortex (tmax=15 min. The ratio of the AUCbrain dialysates value between i.n. route and i.v. injection was 0.68, which was greater than that obtained after i.g. administration (0.43. The systemic bioavailability obtained with i.n. administration was greater than that obtained by the i.g. route (86.33% vs. 50.39%, whereas the DTE of the nasal route was 78.89%, close to that of oral administration (85.69%. These results indicate that TMPP is rapidly absorbed from the nasal mucosa into the systemic circulation, and then crosses the blood–brain barrier (BBB to reach the cerebral cortex. Intranasal administration of TMPP could be a promising alternative to intravenous and oral approaches.

  20. Determination of Clarithromycin in Human Plasma by Liquid Chromatography-Tandem Mass Spectrometry: Validation and Application in Clinical Pharmacokinetic Study

    Institute of Scientific and Technical Information of China (English)

    ZHANGXiang-rong; CHENXiao-yan; LIXiao-yan; ZHONGDa-fang

    2004-01-01

    Aim To develop a liquid chromatographic-tandem mass spectrometric (LC-MS-MS) method to determine clarithromycin in human plasma. Methods The analyte and internal standard roxithromycin were extracted from plasma samples by n-nexane-dichloromethane-isopropanel (300:150:15, V/V/V) and chromatographed on a C18 column. The mobile phase consisted of methanol-water-formic acid (80:20:1, V/V/V). Detection was performed on a triple quadrupole tandem mass spectrometer via electrospray ionization source (ESI) in the positive mode. Results The method had a lower limit of quantification of 10.0 ng·mL-1 when 0.2 mL plasma was used. The linear calibration curves were obtained in the concentration range of 10.0-5000 ng·mL-1. The intra-and inter-rum precisions were lower than 3.3% in terms of relative standard deviation (RSD), and the accuracy ranged±0.7% in terms of relative error (RE). Tmax, Cmax, T1/2 and AUC0-24h values were found to be (3.1±2.7)h, (8 750±4 734)ng·mL-1, (5.3±2.2)h, and (5932±2 449)ng·mL-1, respectively, after a single oral dose of 250 mg clarithromycin tablet to 18 volunteers. Conclusion This validated method was successful in the evaluation of pharmacokinetic profiles of clarithromycin tablets administered to 18 healthy male volubteers.

  1. Development and Validation of a HPLC Method to Determine Griseofulvin in Rat Plasma: Application to Pharmacokinetic Studies

    Directory of Open Access Journals (Sweden)

    Bo Wei

    2008-01-01

    Full Text Available A simple, specific, sensitive, and rapid high performance liquid chromatography (HPLC method for the determination of griseofulvin in small volumes of rat plasma was developed and validated using warfarin as an internal standard. Biological sample preparation involved simple extraction with acetonitrile, followed by dilution with aqueous mobile phase buffer (20 mM sodium dihydrogen phosphate, pH 3.5 to eliminate any chromatographic solvent effects. Griseofulvin and warfarin were baseline separated and quantitated on a C18 reversed phase column (4.6 × 150 mm, 3.5 µ m, using a mobile phase composed of a 20 mM aqueous solution of sodium dihydrogen phosphate-acetonitrile (55:45, v/v, pH 3.5 delivered at a flow rate of 1.0 mL/min, and with fluorescence detection (λexcitation = 300 nm, λemission = 418 nm. The method was proven to be linear over a plasma griseofulvin concentration range of 10 to 2500 ng/mL with a mean correlation coefficient of 0.9996. The intra-day and inter-day accuracy (relative error were in the range of 0.89% to 9.26% and 0.71% to 7.68%, respectively. The within-day precision (coefficient of variation was less than 3.0% and the between-day precision was less than 7.5%. The mean recovery of griseofulvin from rat plasma was found to be 99.2%. The limit of detection (LOD and the limit of quantification (LOQ of griseofulvin were determined to be 1 ng/mL and 10 ng/mL, respectively. The developed method was successfully applied to quantitatively assess the pharmacokinetics of griseofulvin in rats following a single 50 mg/kg oral dose of the drug.

  2. Studies on separation and pharmacokinetics of m-nisoldipine enantiomers in beagle dog plasma by LC/MS/MS.

    Science.gov (United States)

    Li, Min; Yuan, Lin; Li, Xiuqing; Zhi, Xuran; Sheng, Ning; Zhang, Lantong

    2013-11-01

    A rapid, sensitive and selective liquid chromatography-tandem mass spectrometric (LC/MS/MS) method was developed and validated for the separation and determination of m-nisoldipine enantiomers in beagle dog plasma. Samples were pretreated by a single-step protein precipitation with acetonitrile. After m-nisoldipine racemic administration to beagle dogs, samples of m-nisoldipine enantiomers in beagle dog plasma were separated and determined on a ULTRON ES-OVM column (150 × 4.6 mm, 5 μm) at 20°C with a mobile phase consisted of methanol-acetonitrile-ammonium acetate (pH 7.0; 2mM) (15:15:70, v/v/v) at a flow rate of 0.8 mL/min. Chromatograms were monitored at 237 nm, and the API 4000 triple quadrupole mass spectrometer was operated in multiple reaction monitoring (MRM) scan mode using ElectroSpray ionization (ESI) source. The good linearity (rs=0.9958 and rr=0.9983) were found in the range 0.25-20 ng/mL. The lower limit of quantification (LLOQ) obtained was 0.25 ng/mL (n=6). All the validation data, such as accuracy, precision, intra-day and inter-day repeatability, were within the required limits. The method was successfully applied to separation and pharmacokinetics of m-nisoldipine enantiomers in beagle dog plasma. The result of statistics analysis shows that there are no significant differences between R-(-)-m-nisoldipine and S-(+)-m-nisoldipine (p>0.05). The study provides necessary evidences for the research and new drug development of m-nisoldipine enantiomers.

  3. Multi-parameter gradient procedure for polarimetry data inversion in tokamak plasma

    Energy Technology Data Exchange (ETDEWEB)

    Chrzanowski, J., E-mail: j.chrzanowski@am.szczecin.pl [Maritime University, Szczecin Wały Chrobrego 1/2 (Poland); Kravtsov, Yu. A. [Maritime University, Szczecin Wały Chrobrego 1/2 (Poland); Mazon, D. [Association Euratom/CEA, CEA Cadarache DSM/IRFM, 13108 St. Paul lez Durance Cedex (France); JET, Culham (United Kingdom)

    2013-10-15

    Highlights: ► We use gradient procedure to fit plasma parameters to polarimetric data. ► Calculations are performed in developed by authors angular variables technique. ► Numerical results are compared with experimentally measured angular parameters. ► We observe satisfied accuracy of inversion procedure after several iterations. -- Abstract: Multi-parameter gradient procedure is suggested which allows fitting tokamak plasma model to polarimetric data. One of the simplest version of gradient procedure deals with four parameters model: maximum values of electron density, maximum value of electric current density in plasma, common radius of electron density, electric current distributions and increment of the safety factor inside plasma. Using recently developed by authors angular variables technique (AVT) in plasma polarimetry we may compute angular parameters of polarization ellipse for a given set of four plasma parameters and compare them with experimentally measured angular parameters. With angular parameters, measured in two channels polarimetric system (two azimuthal and two ellipticity angles, totally four experimental values). Applying then gradient procedure for squared difference between computed and measured parameters, we find four parameters of plasma model and thereby perform inversion of polarimetric data. Numerical simulations have approved that gradient procedure provides acceptable accuracy of inversion already after several iterations.

  4. A Systematic Analysis of the Sensitivity of Plasma Pharmacokinetics to Detect Differences in the Pulmonary Performance of Inhaled Fluticasone Propionate Products Using a Model-Based Simulation Approach

    OpenAIRE

    Weber, Benjamin; Hochhaus, Guenther

    2015-01-01

    The role of plasma pharmacokinetics (PK) for assessing bioequivalence at the target site, the lung, for orally inhaled drugs remains unclear. A validated semi-mechanistic model, considering the presence of mucociliary clearance in central lung regions, was expanded for quantifying the sensitivity of PK studies in detecting differences in the pulmonary performance (total lung deposition, central-to-peripheral lung deposition ratio, and pulmonary dissolution characteristics) between test (T) an...

  5. Application of a physiologically based pharmacokinetic model for the evaluation of single-point plasma phenotyping method of CYP2D6.

    Science.gov (United States)

    Chen, Rui; Rostami-Hodjegan, Amin; Wang, Haotian; Berk, David; Shi, Jun; Hu, Pei

    2016-09-20

    Determining metabolic ratio from single-point plasma is potentially a good phenotyping method of CYP2D6 to reduce the required time interval and increase the reliability of data. It is difficult to conduct large sample size clinical trials to evaluate this phenotyping method for multiple plasma points. A physiologically based pharmacokinetic (PBPK) model can be developed to do simulations based on the large virtual Chinese population and evaluate single-point plasma phenotyping method of CYP2D6. Pharmacokinetic data of dextromethorphan (DM) and its metabolite dextrorphan (DX) after oral administration were used for model development. The SimCYP® model incorporating Chinese demographic, physiological, and enzyme data was used to simulate DM and DX pharmacokinetics in different phenotype groups. The ratios of the simulated to the observed mean AUC and Cmax of DM were 1.01 and 0.81 for extensive metabolizers (EMs), 0.90 and 0.81 for intermediate metabolizers (IMs), and 1.12 and 0.84 for poor metabolizers (PMs). The ratios of the simulated to the observed mean AUC and Cmax of DX were 1.12 and 0.89 for EMs, 0.66 and 0.62 for IMs. All ratios were within the predefined criterion of 0.5-2. The simulations of DM and DX pharmacokinetic profiles in 1000 virtual Chinese subjects with reported frequencies of different phenotypes indicated that statistically significant correlations were found between metabolic ratio of DM to DX (MRDM/DX) from AUC and from single-point plasma from 1 to 30h (all p-values phenotyping method of CYP2D6 for EMs, IMs, and PMs. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Numerical estimation of the noncompartmental pharmacokinetic parameters variance and coefficient of variation of residence times.

    Science.gov (United States)

    Purves, R D

    1994-02-01

    Noncompartmental investigation of the distribution of residence times from concentration-time data requires estimation of the second noncentral moment (AUM2C) as well as the area under the curve (AUC) and the area under the moment curve (AUMC). The accuracy and precision of 12 numerical integration methods for AUM2C were tested on simulated noisy data sets representing bolus, oral, and infusion concentration-time profiles. The root-mean-squared errors given by the best methods were only slightly larger than the corresponding errors in the estimation of AUC and AUMC. AUM2C extrapolated "tail" areas as estimated from a log-linear fit are biased, but the bias is minimized by application of a simple correction factor. The precision of estimates of variance of residence times (VRT) can be severely impaired by the variance of the extrapolated tails. VRT is therefore not a useful parameter unless the tail areas are small or can be shown to be estimated with little error. Estimates of the coefficient of variation of residence times (CVRT) and its square (CV2) are robust in the sense of being little affected by errors in the concentration values. The accuracy of estimates of CVRT obtained by optimum numerical methods is equal to or better than that of AUC and mean residence time estimates, even in data sets with large tail areas.

  7. Mechanism-based pharmacokinetic-pharmacodynamic modeling of salvianolic acid A effects on plasma xanthine oxidase activity and uric acid levels in acute myocardial infarction rats.

    Science.gov (United States)

    Wang, Haidong; Li, Xi; Zhang, Wenting; Liu, Yao; Wang, Shijun; Liu, Xiaoquan; He, Hua

    2017-03-01

    1. Salvianolic acid A (SalA) was found to attenuate plasma uric acid (UA) concentration and xanthine oxidase (XO) activity in acute myocardial infraction (AMI) rats, which was characterized with developed mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) model. 2. AMI was induced in rats by coronary artery ligation. Surviving AMI rats received a single intravenous dose of 5 mg/kg of SalA and normal saline. The plasma SalA concentrations were determined by HPLC-MS/MS method. The plasma UA concentrations were determined by HPLC method and plasma XO activity were measured spectrophotometrically. An integrated mathematical model characterized the relationship between plasma UA and SalA. 3. Pharmacokinetics was described using two-compartment model for SalA with linear metabolic process. In post-AMI rats, XO activity and UA concentrations were increased, while SalA dosing palliated this increase. These effects were well captured by using two series of transduction models, simulating the delay of inhibition on XO driven by SalA and UA elevation resulted from the multiple factors, respectively. 4. The effect was well described by the developed PK-PD model, indicating that SalA can exert cardiovascular protective effects by decreasing elevated plasma UA levels induced by AMI.

  8. Synthesis of Single Wall Carbon Nanotubes by Plasma Arc: Role of Plasma Parameters

    Science.gov (United States)

    Farhart, Samir; Scott, Carl D.

    2000-01-01

    Single wall carbon nanotubes (SWNT) are porous objects on the molecular scale and have a low density, which gives them potential applications as adsorbent for molecular hydrogen. Their H2 absorption capacity published in the literature varies from 4 to 10% by mass according to the purity of the materials and storage conditions. Optimization of production methods of SWNTs should permit improving these new materials for storage of hydrogen. In this article, we show the potential of using SWNTs in hydrogen storage. In particular, we pose problems associated with synthesis, purification, and opening up of the nanotubes. We present an electric arc process currently used at laboratory scale to produce single wall carbon nanotubes. We discuss, in particular, operating conditions that permit growth of nanotubes and some plasma parameters that assure control of the material. Analysis of the process is carried out with the aid of local measurements of temperature and scanning and transmission electron microscopy of the materials.

  9. Comparative pharmacokinetics and bioavailability of albendazole sulfoxide in sheep and goats, and dose-dependent plasma disposition in goats.

    Science.gov (United States)

    Aksit, Dilek; Yalinkilinc, Hande Sultan; Sekkin, Selim; Boyacioğlu, Murat; Cirak, Veli Yilgor; Ayaz, Erol; Gokbulut, Cengiz

    2015-05-27

    The aims of this study were to compare the pharmacokinetics of albendazole sulfoxide (ABZ-SO, ricobendazole) in goats and sheep at a dose of 5 g/kg bodyweight (BW), after intravenous (IV) and subcutaneous (SC) administrations, and to investigate the effects of increased doses (10 and 15 mg/kg BW) on the plasma disposition of ABZ-SO in goats following SC administration. A total of 16 goats (Capra aegagrus hircus, eight males and eight females) and 8 sheep (Ovis aries, four males and four females) 12-16 months old and weighing 20-32 kg, were used. The study was designed according to two-phase crossover study protocol. In Phase-1, eight sheep were assigned as Group I and 16 goats were allocated into two groups (Group II and Group III). ABZ-SO was applied to Group I (sheep) and Group II (goats) animals subcutaneously, and to Group III (goats) animals intravenously, all at a dose rate of 5 mg/kg BW. In Phase-2, the sheep in the Group I received ABZ-SO intravenously in a dose of 5 mg/kg BW; the goats in Group II and Group III received ABZ-SO subcutaneously at a dose of 10 mg/kg and 15 mg/kg BW, respectively. Blood samples were collected from the jugular vein at different times between 1 and 120 h after drug administrations. The plasma concentrations of ABZ-SO and its metabolites were analysed by high performance liquid chromatography. In goats, the area under the curve, terminal half-life and plasma persistence of ABZ-SO were significantly smaller and shorter, respectively, compared with those observed in sheep following both IV and SC administrations at a dose of 5 mg/kg BW. On the other side, dose-dependent plasma dispositions of ABZ-SO were observed following SC administration at increased doses (10 and 15 mg/kg) in goats. Consequently, ABZ-SO might be used at higher doses to provide higher plasma concentration and thus to achieve greater efficacy against the target parasites.

  10. First report on the pharmacokinetics of tramadol and O-desmethyltramadol in exhaled breath compared to plasma and oral fluid after a single oral dose.

    Science.gov (United States)

    Meyer, Markus R; Rosenborg, Staffan; Stenberg, Marta; Beck, Olof

    2015-12-01

    Exhaled breath (EB) is a promising matrix for bioanalysis of non-volatiles and has been routinely implemented for drugs of abuse analysis. Nothing is known regarding the pharmacokinetics of therapeutics and their metabolites in EB. Therefore, we used tramadol as a model drug. Twelve volunteers received a single oral dose of tramadol and repeated sampling of EB, plasma, and oral fluid (OF) was done for 48 h using a particle filter device for EB and the Quantisal-device for OF. Samples were analyzed with LC-MS/MS and the pharmacokinetic correlations between matrices were investigated. The initial tramadol half-life in EB was shorter than in plasma but it reappeared in EB after 8-24 h. The ratio of O-desmethyltramadol to tramadol was considerably lower in EB and OF compared to plasma. This pilot study compared for the first time the pharmacokinetics of a therapeutic drug and active metabolite in different biomatrices including EB and demonstrated its potential for bioanalysis.

  11. Simultaneous determination of leucine, isoleucine and valine in Beagle dog plasma by HPLC-MS/MS and its application to a pharmacokinetic study.

    Science.gov (United States)

    Wang, Ting; Xie, Huiru; Chen, Xu; Jiang, Xuehua; Wang, Ling

    2015-10-10

    Leucine (Leu), isoleucine (Ile) and valine (Val) are three branched-chain amino acids (BCAAs), which have been widely used as dietary supplements for professional athletes and patients with liver failure or catabolic diseases. To date, no pharmacokinetic studies of BCAAs in vivo useful for the assessment of clinical effect following daily intake has been reported. Thus in this study, an HPLC-MS/MS method for simultaneous determination of Leu, Ile and Val in Beagle dog plasma using homoarginine as the internal standard was developed and validated in terms of specificity, linearity, precision, accuracy, and stability. This assay method was then applied to a pharmacokinetic study of BCAAs in dogs following oral administration of 0.25 g/kg and 0.50 g/kg BCAAs. The HPLC-MS/MS method was found to be sensitive and reproducible for quantification of BCAAs in dog plasma and successfully applied to the pharmacokinetic study. All these BCAAs were well absorbed with a substantial increase in the plasma concentration after a baseline modification. No statistical significance was identified in different gender group and no drug accumulation was observed following multiple doses.

  12. Development and Validation of a LC/MS/MS Method for the Determination of Duloxetine in Human Plasma and Its Application to Pharmacokinetic Study

    Directory of Open Access Journals (Sweden)

    D. Chandrapal Reddy

    2012-01-01

    Full Text Available A selective, high sensitive and high throughput liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS method has been developed and validated for the chromatographic separation and quantitation of duloxetine in human EDTA plasma using fluoxetine (IS as an internal standard. Analyte and IS were extracted from human plasma by liquid-liquid extraction using MTBE-n Hexane (80:20.The eluted samples were chromatographed on X-terra RP8 (50 mmx4.6 mm, 5 μm particle size column by using mixture of 30 mM ammonium formate (pH-5.0±0.05 and acetonitrile as an isocratic mobile phase at a flow rate of 0.40 mL/min and analyzed by mass spectrometer in the multiple reaction monitoring (MRM using the respective m/z 298.08→154.0 for duloxetine and 310.02→148.07 for IS. The linearity of the response/ concentration curve was established in human plasma over the concentration range 0.100-100.017 ng/mL. The lower detection limit (LOD,S/N>3 was 0.04 ng/mL and the lower limit of quantization (LOQ,S/N>10 was 0.100 ng/mL. This LC-MS/MS method was validated with Intra-batch and Inter-batch precision of 5.21-7.02. The Intra-batch and Inter-batch accuracy was 97.14-103.50 respectively. Recovery of duloxetine in human plasma is 80.31% and ISTD recovery is 81.09%. The main pharmacokinetic parameters were Tmax (hr = (7.25±1.581, Cmax (ng/mL (44.594±18.599, AUC0→t, = (984.702±526.502 and AUC0→∞, (1027.147±572.790 respectively.

  13. Ethnic and genetic factors in methadone pharmacokinetics: a population pharmacokinetic study.

    Science.gov (United States)

    Bart, Gavin; Lenz, Scott; Straka, Robert J; Brundage, Richard C

    2014-12-01

    Treatment of opiate use disorders with methadone is complicated by wide interindividual variability in pharmacokinetics. To identify potentially contributing covariates in methadone pharmacokinetics, we used population pharmacokinetic modeling to estimate clearance (CL/F) and volume of distribution (V/F) for each methadone enantiomer in an ethnically diverse methadone maintained population. Plasma levels of the opiate-active R-methadone and opiate-inactive S-methadone were measured in 206 methadone maintained subjects approximately two and twenty-three hours after a daily oral dose of rac-methadone. A linear one-compartment population pharmacokinetic model with first-order conditional estimation with interaction (FOCE-I) was used to evaluate methadone CL/F and V/F. The influence of covariates on parameter estimates was evaluated using stepwise covariate modeling. Covariates included ethnicity, gender, weight, BMI, age, methadone dose, and 21 single nucleotide polymorphisms in genes implicated in methadone pharmacokinetics. In the final model, for each enantiomer, Hmong ethnicity reduced CL/F by approximately 30% and the rs2032582 (ABCB1 2677G>T/A) GG genotype was associated with a 20% reduction in CL/F. The presence of the rs3745274 minor allele (CYP2B6 515G>T) reduced CL/F by up to 20% for S-methadone only. A smaller effect of age was noted on CL/F for R-methadone. This is the first report showing the influence of the rs2032582 and rs3745274 variants on methadone pharmacokinetics rather than simply dose requirements or plasma levels. Population pharmacokinetics is a valuable method for identifying the influences on methadone pharmacokinetic variability. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Pharmacokinetics of eprinomectin in plasma and milk following subcutaneous administration to lactating dairy cattle.

    Science.gov (United States)

    Baoliang, P; Yuwan, W; Zhende, P; Lifschitz, A L; Ming, W

    2006-04-01

    Eprinomectin is only available as a topically applied anthelmintic for dairy cattle. To determine whether eprinomectin can be applied as an injectable formulation in dairy cattle, a novel injectable formulation was developed and was subcutaneously delivered to four lactating dairy cattle at a dose rate of 0.2 mg/ kg. Plasma and milk samples were collected. The concentrations of eprinomectin in all samples were determined by HPLC. The peak plasma concentration (C(max))of 44.0+/-24.2 ng/ml occurred 39+/-19.3 h after subcutaneous administration, equivalent to the C(max) (43.76+/-18.23 ng/ml) previously reported for dairy cattle after a pour-on administration of 0.5 mg/kg eprinomectin. The area under the plasma concentration-time curve (AUC) after subcutaneous administration was 7354+/-1861 (ng h)/ml, higher than that obtained after pour-on delivery (5737.68+/-412.80 (ng h)/ml). The mean residence time (MRT) of the drug in plasma was 211+/-55.2 h. Eprinomectin was detected in the milk at the second sampling time. The concentration of drug in milk was parallel to that in plasma, with a milk to plasma ratio of 0.16+/-0.01. The highest detected concentration of eprinomectin in milk was 9.0 ng/ml, below the maximum residue limit (MRL) of eprinomectin in milk established by the Joint FAO/WHO Expert Committee on Food Additives in 2000. The amount of eprinomectin recovered in the milk during this trial was 0.39%+/-0.08% of the total administered dose. This study demonstrates that subcutaneous administration of eprinomectin led to higher bioavailability and a lower dose than a pour-on application, and that an injectable formulation of eprinomectin may be applied in dairy cattle with a zero withdrawal period.

  15. Pharmacokinetics and bioavailability of drotaverine in humans.

    Science.gov (United States)

    Bolaji, O O; Onyeji, C O; Ogundaini, A O; Olugbade, T A; Ogunbona, F A

    1996-01-01

    The pharmacokinetics and bioavailability of drotaverine was studied in 10 healthy volunteers after administration of single 80 mg oral and intravenous doses of the HCl salt of the drug, in a crossover fashion. Plasma and urine samples were analyzed for the unchanged drug by HPLC. The pharmacokinetic parameters, such as elimination half-life, plasma clearance, renal clearance and apparent volume of distribution, were not influenced by the route of drug administration. The drug was mainly eliminated by non-renal routes since renal clearance accounted for only 0.31 +/- 0.13% of the total plasma clearance. The absolute bioavailability was variable and ranged from 24.5-91% with a mean of 58.2 +/- 18.2% (mean +/- SD). It is suggested that the high variation in the bioavailability of drotaverine HCl after oral administration may result in significant interindividual differences in therapeutic response.

  16. [Plasma pharmacokinetics of roxatidine in the healthy man: correlation with gastric antisecretory effect].

    Science.gov (United States)

    Chen, W W; Kolsky, H; Lewin, M J; Bonfils, S

    1990-01-01

    Inhibitory effects of roxatidine acetate upon human gastric secretion have been shown to be dose-related after oral administration. In order to correlate this effect with drug pharmacokinetics, blood concentration of the active metabolite, roxatidine, was assessed in 10 healthy volunteers, each receiving in random order 75, 150, 300, 600 mg of roxatidine acetate and placebo. Blood was drawn for roxatidine measurement at T 0 (time of drug intake) T 75, 90, 120, 150, 210, 240 and 300 min. Meal-induced gastric secretion was studied by intragastric titration (IGT) at 15 min intervals, from T 150 to T 240. Mean peak of blood concentration occurred at T 150 with significant correlation with the administered dosage. Gastric secretion inhibition over the 90 min of IGT correlated with peak concentration exclusively for the subpopulation with peak occurrence at T 150. Beyond the peak, decrease in roxatidine concentrations was slow, as expected from a known 6-h half-life. However, overall results showed that mean blood concentration was correlated with gastric secretion inhibition from T 180 on. The last IGT sample also correlated with the peak. Interpretation of these results would be different whether roxatidine concentration variations are appreciated as exhibiting a significant decrease or not. Infusion studies of roxatidine would be a valuable technique for further analysis and comparison of blood-concentration/efficacy relationships as compared with other H2-antagonists.

  17. Erythrocytes encapsulated with phenylalanine hydroxylase exhibit improved pharmacokinetics and lowered plasma phenylalanine levels in normal mice.

    Science.gov (United States)

    Yew, Nelson S; Dufour, Emmanuelle; Przybylska, Malgorzata; Putelat, Julie; Crawley, Cristin; Foster, Meta; Gentry, Sarah; Reczek, David; Kloss, Alla; Meyzaud, Aurélien; Horand, Françoise; Cheng, Seng H; Godfrin, Yann

    2013-08-01

    Enzyme replacement therapy is often hampered by the rapid clearance and degradation of the administered enzyme, limiting its efficacy and requiring frequent dosing. Encapsulation of therapeutic molecules into red blood cells (RBCs) is a clinically proven approach to improve the pharmacokinetics and efficacy of biologics and small molecule drugs. Here we evaluated the ability of RBCs encapsulated with phenylalanine hydroxylase (PAH) to metabolize phenylalanine (Phe) from the blood and confer sustained enzymatic activity in the circulation. Significant quantities of PAH were successfully encapsulated within murine RBCs (PAH-RBCs) with minimal loss of endogenous hemoglobin. While intravenously administered free PAH enzyme was rapidly eliminated from the blood within a few hours, PAH-RBCs persisted in the circulation for at least 10days. A single injection of PAH-RBCs was able to decrease Phe levels by nearly 80% in normal mice. These results demonstrate the ability of enzyme-loaded RBCs to metabolize circulating amino acids and highlight the potential to treat disorders of amino acid metabolism.

  18. The pharmacokinetic screening of multiple components of the Nao Mai Tong formula in rat plasma by liquid chromatography tandem mass spectrometry combined with pattern recognition method and its application to comparative pharmacokinetics.

    Science.gov (United States)

    Wu, Chunwei; Zhao, Lu; Rong, Yueying; Zhu, Guoxue; Liang, Shengwang; Wang, Shumei

    2016-11-30

    The Nao Mai Tong formula (NMT) is composed of Rhubarb, Ginseng, Ligusticum wallichii and Pueraria in a ratio of 3:3:2:2 (w/w) and is a well-known traditional Chinese prescription that has been clinically employed for treating ischemia cerebrovascular disease. The goal of this study was to investigate the pharmacokinetics of multiple components (chryohol-8-O-β-D-glucoyroide, physcion-8-O-β-D-glucopyranoside, aloe-emodin, rhein, emodin, chrysophanol, ginsenoside Rg1, ginsenoside Rb1, ginsenoside Rb3, ginsenoside Rc, senkyunolide I, ligustilide puerarin, daidzein, 3'-methoxy puerarin) after the oral administration of the NMT formula in rats. A rapid and sensitive UHPLC-Quadrupole-Orbitrap-MS with a sequential positive and negative ionization mode was developed to determine the 15 absorbed ingredients. After extraction from blood, the analytes and internal standards were subjected to ultra-high performance liquid chromatography with Agela Venusil MPC18 (2.1mm×100mm, 3μm, Agela, USA). The mobile phase consisted of methanol and ammonium acetate (3mmolL(-1)) under gradient elution conditions. This validated method was successfully applied to a comparative pharmacokinetic study of fifteen components in rat plasma after oral administration of the NMT formula or single herb extracts to normal and stroke-afflicted rats. A principal component analysis (PCA) was utilized to evaluate the differences in the pharmacokinetic behavior (time-course) of the absorbed components of NMT, and the absorbed components were assigned to 3 separate clusters. A comparison of the body dynamics of each group indicated that cluster B (ginsenoside Rg1, ginsenoside Rb1, ginsenoside Rb3, ginsenoside Rc) might be the most important constituents controlling the pharmacological effects of NMT. The comparative pharmacokinetic study showed that the different groups had different pharmacokinetic characteristics. The pharmacokinetics-based UHPLC Quadrupole-Orbitrap-MS using a full-scan mode combined

  19. 蟾酥提取物中2种蟾蜍甾烯类成分兔体内药代动力学研究%Studies on Simultaneous Determination and Pharmacokinetics of Two Bufadienolides in Rabbits Plasma

    Institute of Scientific and Technical Information of China (English)

    刘冬; 杜守颖; 何秀峰; 王爱国; 李娜

    2011-01-01

    Objective:To establish a HPLC method for the assay of bufalin (BL) , resibufogenin (RBC) and study the pharmacokinetics of BL, RBC in rabbits plasma. Method; The sample blood from rabbits were injected venenum bufonis extract by 0*. 35 mg'kg~'at 2,5,10,15,20,30,45,60,90 min. Protein precipitation with acetonitrile and liquid-liquid extraction was applied to purify plasma samples and used HPLC to determine the concentration of BL, RBG in it. The pharmacokinetics parameters were accessed by Kinetica software. Result; In this HPLC method, the separation, precision and accuracy of BL, RBG were well. The calibration curves were linear. The analytical recoveries were all more than 90% , intra and inter-day precision RSD were all less than 15. 0% (n =5). The main pharmacokinetics parameters were fitted by non-compartment models. Conclusion; The. HPLC method can be used to determine the concentration and to investigate the pharmacokinetics of BL and RBG.%目的:建立兔血浆中2种蟾蜍甾烯类化合物蟾毒灵及酯蟾毒配基的分析方法,探讨其在兔体内的药代动力学过程.方法:兔按0.35 mg·kg-1由耳缘静脉注射蟾酥提取物后分别于2,5,10,15,20,30,45,60,90 min心脏取血,采用乙腈沉蛋白与液液萃取相结合方法进行血浆样品预处理,以HPLC测定兔血浆中蟾毒灵及酯蟾毒配基的浓度,以Kinetica软件拟合药动学参数.结果:建立的HPLC方法,蟾毒灵、酯蟾毒配基均得到很好的分离,达到体内分析要求.经非房室模型拟合,得到了蟾毒灵、酯蟾毒配基在兔体内主要药动学参数.结论:建立的蟾毒灵、酯蟾毒配基血药浓度测定方法及所获得的药动学参数,可为中药蟾酥提取物的药代动力学研究提供参考.

  20. Determination of swertianolin in rat plasma by LC-MS/MS and its application to a pharmacokinetic study.

    Science.gov (United States)

    He, Jun; Tian, Chengwang; Ouyang, Huizi; Adelakun, Tiwalade A; Yu, Bin; Chang, Yanxu; Pan, Guixiang; Jiang, Linghuo; Gao, Xiumei

    2014-10-01

    A sensitive and rapid LC-MS/MS method has been developed and validated for quantifying swertianolin in rat plasma using rutin as an internal standard (IS). Following liquid-liquid extraction with ethyl acetate, chromatographic separation for swertianolin was achieved on a C18 column with a gradient elution using 0.1% formic acid as mobile phase A and acetonitrile as mobile phase B at a flow rate of 0.3 mL/min. The detection was performed on a tandem mass spectrometer using multiple reaction monitoring via an electrospray ionization source and operating in the negative ionization mode. The optimized mass transition ion pairs (m/z) for quantitation were 435.1/272.0 for swertianolin and 609.2/300.1 for IS. The lower limit of quantitation was 0.5 ng/mL within a linear range of 0.5-500 ng/mL. Intra-day and inter-day precision was less than 6.8%. The accuracy was in the range of -13.9 to 12.0%. The mean recovery of swertianolin was >66.7%. The proposed method was successfully applied in evaluating the pharmacokinetics of swertianolin after an oral dose of 50 mg/kg Swertia mussotii extract in rats.

  1. Determination of Sertraline in Human Plasma by UPLC-MS/MS and its Application to a Pharmacokinetic Study.

    Science.gov (United States)

    Yue, Xiao-Hong; Wang, Zhen; Tian, Dong-Dong; Zhang, Jian-Wei; Zhu, Kang; Ye, Qiang

    2016-02-01

    A sensitive and rapid ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS-MS) method was developed to determine sertraline in human plasma. Sample preparation was accomplished through a simple liquid-liquid extraction with ethyl acetate. Chromatographic separation was carried out on an Acquity UPLC BEH C18 column using a gradient mobile phase system composed of acetonitrile and 1% formic acid in water at a flow rate of 0.40 mL/min. Mass spectrometric analysis was performed using a XEVO TQD mass spectrometer coupled with an electrospray ionization source in the positive ion mode. The multiple reaction monitoring transitions of m/z 306.3 → 275.2 and 326.2 → 291.1 were used to quantify for sertraline and midazolam (internal standard), respectively. The linearity of this method was found to be within the concentration range of 1.0-100.0 ng/mL with a lower limit of quantification of 1.0 ng/mL. Only 2.0 min was needed for an analytical run. This fully validated method was successfully applied to the pharmacokinetic study after an oral administration of 100 mg sertraline to 20 Chinese healthy male volunteers.

  2. UPLC-MS/MS determination of phentolamine in human plasma and its application to a pharmacokinetic study.

    Science.gov (United States)

    Kan, X; Zheng, S-L; Zhou, C-Y

    2014-11-01

    A sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed to determine phentolamine in human plasma. Sample preparation was accomplished through a simple liquid-liquid extraction with ethyl acetate. Chromatographic separation was carried out on an Acquity UPLC BEH C18 column using an isocratic mobile phase system composed of acetonitrile and 1% formic acid in water (33:67, v/v) at a flow rate of 0.45 mL/min. Mass spectrometric analysis was performed using a QTrap5500 mass spectrometer coupled with an electro-spray ionization (ESI) source in the positive ion mode. The MRM transitions of m/z 282.1 → 212.0 and m/z 237.1 → 194.2 were used to quantify for phentolamine and carbamazepine (internal standard, IS), respectively. The linearity of this method was found to be within the concentration range of 0.5-100.0 ng/mL with a lower limit of quantification of 0.5 ng/mL. Only 1.0 min was needed for an analytical run. This fully validated method was successfully applied to the pharmacokinetic study after oral administration of 60 mg phentolamine to 20 Chinese healthy male volunteers.

  3. Preclinical pharmacokinetic analysis of armillarisin succinate ester in mouse plasma and tissues by LC-MS/MS.

    Science.gov (United States)

    Chen, Qinhua; Li, Peng; Zhang, Jinfeng; Zhu, Jun

    2013-01-01

    A liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed and validated to determine the concentration of armillarisin succinate ester in mouse plasma and tissues, used for preclinical evaluation. Bavachin was employed as the internal standard. Separation was performed on a 3.5 µm Zorbax SB-C(18) column (30 × 2.1 mm), with a mobile phase consisting of methanol and aqueous 20 mm ammonium acetate. Both analyte and internal standard were determined using electrospray ionization and the MS data acquisition was via selected ion monitoring in negative scanning mode. Quantification was performed using the transitions m/z 333 → 233 and 323 → 221 for armillarisin succinate ester and internal standard, respectively. The method was validated with respect to linearity, accuracy, precision, recovery and stability. This assay has been successfully applied to a pharmacokinetic and tissue distribution study after intravenous injection of ASE in mouse in a dose of 10 mg/kg. Copyright © 2012 John Wiley & Sons, Ltd.

  4. Determination of cyclovirobuxine D in human plasma by liquid chromatography tandem mass spectrometry and application in a pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Ling-li Mu

    2011-10-01

    Full Text Available A sensitive and reliable method based on liquid chromatography tandem mass spectrometry (LC–MS/MS for the quantitation of cyclovirobuxine D in human plasma has been developed and validated. Sample preparation by solid phase extraction was followed by separation on a CN column with a mobile phase of methanol–water (95:5, v/v containing 0.2% formic acid. Mass spectrometric detection in the positive ion mode was carried out by selected reaction monitoring (SRM of the transitions at m/z 403.0→372.0 for cyclovirobuxine D and m/z 325.0→234.0 for citalopram (internal standard. The method was linear in the range 10–200 ng/L with LLOQ of 10 ng/L, recovery >85%, and no significant matrix effects. Intra- and inter-day precisions were all <9% with accuracies of 94.0–104.8%. The method was successfully applied to a pharmacokinetic study involving a single oral administration of a 2 mg cyclovirobuxine D tablet to twenty-two healthy Chinese volunteers.

  5. Comparative plasma and interstitial fluid pharmacokinetics of flunixin meglumine and ceftiofur hydrochloride following individual and co-administration in dairy cows.

    Science.gov (United States)

    Gorden, P J; Kleinhenz, M D; Wulf, L W; Rajewski, S J; Wang, C; Gehring, R; Coetzee, J F

    2017-07-21

    Ceftiofur (CEF) and flunixin meglumine (FLU) are two drugs approved for use in beef and dairy cattle that are frequently used in combination for many diseases. These two drugs are the most commonly used drugs in dairy cattle in their respective drug classes. Two research groups have recently published manuscripts demonstrating altered pharmacokinetics of FLU and CEF in cows affected with naturally occurring mastitis. The objective of this study was to determine whether pharmacokinetics of flunixin meglumine administered intravenously or intramuscularly administered ceftiofur hydrochloride would be altered when co-administered versus individual administration to healthy dairy cattle. Ten cows were utilized in a three-period, three-treatment crossover design, with all cows receiving each treatment one time with a 10-day washout period between treatments. Following treatment, plasma and interstitial fluid samples were collected and stored for later analysis. Additionally, plasma ultrafiltrate was collected using microcentrifugation to determine plasma protein binding of each drug. Drug concentrations in plasma, plasma ultrafiltrate, and interstitial fluid were determined using high-pressure liquid chromatography coupled with mass spectrometry. The results of this trial indicate that drug interactions between FLU and CEF do not occur when the two drugs are administered simultaneously in healthy cattle. Further work is needed to determine whether this relationship is maintained in the presence of severe disease. © 2017 John Wiley & Sons Ltd.

  6. Simultaneous Determination and Pharmacokinetics of Metolazone, Losartan and Losartan Carboxylic Acid in Rat Plasma by HPLC-ESI-MS-MS.

    Science.gov (United States)

    Dubey, Ramkumar; Ghosh, Manik; Sinha, Barij Nayan; Muthukrishnan, Venkateswari

    2015-10-01

    For the first time, we developed and validated a highly sensitive, selective and rapid HPLC-ESI-MS-MS method for simultaneous quantification of metolazone (MET), losartan (LOS) and its metabolite losartan carboxylic acid (LCA) in rat plasma. After solid-phase extraction, the analytes and internal standard (irbesartan) were extracted from 100 µL plasma sample on an Agilent Poroshell 120, EC-C18 (50 × 4.6 mm, i.d., 2.7 µm) column using 5 µL injection volume with a total run time of 3 min. Acidified methanol/water mixture was used as a mobile phase. The parent → product ion transitions for MET (m/z 366.0 → 258.9), LOS (m/z 423.2 → 207.0), LCA (m/z 437.0 → 235.1) and IS (m/z 429.2 → 207.0) were monitored on a triple quadrupole mass spectrometer, operating in the multiple reaction monitoring and positive ion mode. The method was found to be linear in the range of 0.05-250 for MET, 2-3,000 for LOS and 4-3,500 ng/mL for LCA. The method was validated with respect to selectivity, linearity, accuracy, precision, recovery and stability according to accepted regulatory guidelines. The described method was successfully applied to preclinical pharmacokinetic studies of analytes after an oral administration of mixture of MET (1 mg/kg) and LOS (10 mg/kg) in rats.

  7. Preclinical pharmacokinetics, tissue distribution and plasma protein binding of sodium (±-5-bromo-2-(α-hydroxypentyl benzoate (BZP, an innovative potent anti-ischemic stroke agent

    Directory of Open Access Journals (Sweden)

    Xin Tian

    2016-08-01

    Full Text Available Sodium (±-5-bromo-2-(α-hydroxypentyl benzoate (BZP is a potential cardiovascular drug and exerts potent neuroprotective effect against transient and long-term ischemic stroke in rats. BZP could convert into 3-butyl-6-bromo-1(3H-isobenzofuranone (Br-NBP in vitro and in vivo. However, the pharmacokinetic profiles of BZP and Br-NBP still have not been evaluated. For the purpose of investigating the pharmacokinetic profiles, tissue distribution and plasma protein binding of BZP and Br-NBP, a rapid, sensitive and specific method based on liquid chromatography coupled to mass spectrometry (LC-MS/MS has been developed for determination of BZP and Br-NBP in biological samples. The results indicated that BZP and Br-NBP showed a short elimination half-life, and pharmacokinetic profile in rats (3, 6 and 12 mg/kg; i.v. and beagle dogs (1, 2 and 4 mg/kg; i.v.gtt were obtained after single dosing of BZP. After multiple dosing of BZP, there was no significant accumulation of BZP and Br-NBP in the plasma of rats and beagle dogs. Following i.v. single dose (6 mg/kg to rats, BZP and Br-NBP were distributed rapidly into all tissues examined, with the highest concentrations of BZP and Br-NBP in lung and kidney, respectively. The brain distribution of Br-NBP in middle cerebral artery occlusion (MCAO rats was more than in normal rats (P<0.05. The plasma protein binding degree of BZP at three concentrations (8000, 20000 and 80000 ng/mL from rat, beagle dog and human plasma were 98.1~98.7%, 88.9~92.7% and 74.8%~83.7% respectively. In conclusion, both BZP and Br-NBP showed short half-life, good dose-linear pharmacokinetic profile, wide tissue distribution and different degree protein binding to various species plasma. This was the first preclinical pharmacokinetic investigation of BZP and Br-NBP in both rats and beagle dogs, which provided vital guidance for further preclinical research and the subsequent clinical trials.

  8. Pharmacokinetics of Aminoglycosides

    Institute of Scientific and Technical Information of China (English)

    Lokangu Lombo(Congo); HE Hua

    2004-01-01

    The Pharmacokinetics informations of aminoglycosides, their monograph and clinical Pharmacokinetics parameters are reported in this review. The Aminoglycosides are highly polarity and in reserve for serious infections caused by aerobic gram-negative bacteria and some gram-positive bacteria but their toxicity are major limitations in clinical use.

  9. Evaluation of IAUGC indices and two DCE-MRI pharmacokinetic parameters assessed by two different theoretical algorithms in patients with brain tumors.

    Science.gov (United States)

    Bergamino, Maurizio; Barletta, Laura; Castellan, Lucio; Saitta, Laura; Mancardi, Giovanni Luigi; Roccatagliata, Luca

    2014-01-01

    Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) quantifies blood-brain barrier (BBB) microvascular permeability in brain tumors where it is structurally and functionally abnormal. Twenty-five patients with glioblastomas (105 regions of interest) were compared using DCE-MRI metrics obtained with Tofts-Kety (TK) and extended TK (ETK) models using different arterial input function assessments and different initial area under the gadolinium curve (IAUGC) indices. Strong correlations between ve and IAUGC90 were found (EKT model: R=0.75 and R=0.69), while correlations of K(trans) with both IAUGC80/90 indices were weak. Differences in the permeability parameters, calculated by these two models, were found. While the IAUGC method can be implemented more easily than pharmacokinetic models, at this time, the IAUGC approach alone does not substitute pharmacokinetic models in BBB permeability characterization.

  10. Avaliação farmacocinética de comprimidos contendo lamivudina e zidovudina em plasma humano Pharmacokinetic evaluation of lamivudine and zidovudine tablets in human plasma

    Directory of Open Access Journals (Sweden)

    João Eudes do Nascimento

    2004-03-01

    Full Text Available Este estudo se propõe a avaliar o perfil farmacocinético de comprimidos contendo lamivudina e zidovudina associados, produzidos pelo Laboratório Farmacêutico do Estado de Pernambuco - LAFEPE. O medicamento foi administrado em 10 voluntários sadios e foram observadas as concentrações plasmáticas dos dois anti-retrovirais durante 12 horas. A partir das concentrações plasmáticas foi possível encontrar os parâmetros farmacocinéticos de ambos os fármacos através de cálculos estatísticos. Os resultados obtidos foram comparados com aqueles resultantes de experimentos realizados por outros autores descritos neste trabalho, em que se verificou não haver diferenças significativas entre os valores encontrados e os descritos na literatura e que o fato dos anti-retrovirais estarem associados na mesma formulação não modificou o perfil cinético de nenhuma das substâncias.The purpose of this work was an evaluation of the pharmacokinetic profile from lamivudine and zidovudine combination tablets, produced by Laboratório Farmacêutico do Estado de Pernambuco - LAFEPE. The formulation was administered in 10 volunteers and the concentration-time serum profile was observed from both antiretroviral agents during 12 hours. From concentration-time serum profile the pharmacokinetic parameters for both drugs were calculated by statistical methods. The results were compared with those from experiments carried out by other authors referred in this paper. Differences between the results obtained herein and those from other authors were not significant. The kinetic profile for both substances was not modified by the anti-retroviral combination.

  11. Paediatric pharmacokinetics: key considerations

    Science.gov (United States)

    Batchelor, Hannah Katharine; Marriott, John Francis

    2015-01-01

    A number of anatomical and physiological factors determine the pharmacokinetic profile of a drug. Differences in physiology in paediatric populations compared with adults can influence the concentration of drug within the plasma or tissue. Healthcare professionals need to be aware of anatomical and physiological changes that affect pharmacokinetic profiles of drugs to understand consequences of dose adjustments in infants and children. Pharmacokinetic clinical trials in children are complicated owing to the limitations on blood sample volumes and perception of pain in children resulting from blood sampling. There are alternative sampling techniques that can minimize the invasive nature of such trials. Population based models can also limit the sampling required from each individual by increasing the overall sample size to generate robust pharmacokinetic data. This review details key considerations in the design and development of paediatric pharmacokinetic clinical trials. PMID:25855821

  12. Integral electrical characteristics and local plasma parameters of a RF ion thruster

    Energy Technology Data Exchange (ETDEWEB)

    Masherov, P. E.; Riaby, V. A., E-mail: riaby2001@yahoo.com [Research Institute of Applied Mechanics and Electrodynamics of the Moscow Aviation Institute (National Research University), Moscow (Russian Federation); Godyak, V. A. [Electrical Engineering and Computer Science Department, University of Michigan, Ann Arbor, Michigan 48109, USA and RF Plasma Consulting, Brookline, Massachusetts 02446 (United States)

    2016-02-15

    Comprehensive diagnostics has been carried out for a RF ion thruster based on inductively coupled plasma (ICP) source with an external flat antenna coil enhanced by ferrite core. The ICP was confined within a cylindrical chamber with low aspect ratio to minimize plasma loss to the chamber wall. Integral diagnostics of the ICP electrical parameters (RF power balance and coil current) allowed for evaluation of the antenna coils, matching networks, and eddy current loss and the true RF power deposited to plasma. Spatially resolved electron energy distribution functions, plasma density, electron temperatures, and plasma potentials were measured with movable Langmuir probes.

  13. Plasma Arc Cutting Dimensional Accuracy Optimization employing the Parameter Design approach

    Directory of Open Access Journals (Sweden)

    Kechagias John

    2017-01-01

    Full Text Available Plasma Arc Cutting (PAC is a thermal manufacturing process used for metal plates cutting. This work experimentally investigates the influence of process parameters onto the dimensional accuracy performance of the plasma arc cutting process. The cutting parameters studied were cutting speed (mm/min, torch standoff distance (mm, and arc voltage (volts. Linear dimensions of a rectangular workpiece were measured after PAC cutting following the full factorial design experimental approach. For each one of the three process parameters, three parameter levels were used. Analysis of means (ANOM and analysis of variances (ANOVA were performed in order for the effect of each parameter on the leaner dimensional accuracy to be assessed.

  14. Dependence of the source performance on plasma parameters at the BATMAN test facility

    Energy Technology Data Exchange (ETDEWEB)

    Wimmer, C.; Fantz, U. [Max-Planck-Institut für Plasmaphysik, Boltzmannstr. 2, 85748 Garching (Germany)

    2015-04-08

    The investigation of the dependence of the source performance (high j{sub H{sup −}}, low j{sub e}) for optimum Cs conditions on the plasma parameters at the BATMAN (Bavarian Test MAchine for Negative hydrogen ions) test facility is desirable in order to find key parameters for the operation of the source as well as to deepen the physical understanding. The most relevant source physics takes place in the extended boundary layer, which is the plasma layer with a thickness of several cm in front of the plasma grid: the production of H{sup −}, its transport through the plasma and its extraction, inevitably accompanied by the co-extraction of electrons. Hence, a link of the source performance with the plasma parameters in the extended boundary layer is expected. In order to characterize electron and negative hydrogen ion fluxes in the extended boundary layer, Cavity Ring-Down Spectroscopy and Langmuir probes have been applied for the measurement of the H{sup −} density and the determination of the plasma density, the plasma potential and the electron temperature, respectively. The plasma potential is of particular importance as it determines the sheath potential profile at the plasma grid: depending on the plasma grid bias relative to the plasma potential, a transition in the plasma sheath from an electron repelling to an electron attracting sheath takes place, influencing strongly the electron fraction of the bias current and thus the amount of co-extracted electrons. Dependencies of the source performance on the determined plasma parameters are presented for the comparison of two source pressures (0.6 Pa, 0.45 Pa) in hydrogen operation. The higher source pressure of 0.6 Pa is a standard point of operation at BATMAN with external magnets, whereas the lower pressure of 0.45 Pa is closer to the ITER requirements (p ≤ 0.3 Pa)

  15. Dependence of the source performance on plasma parameters at the BATMAN test facility

    Science.gov (United States)

    Wimmer, C.; Fantz, U.

    2015-04-01

    The investigation of the dependence of the source performance (high jH-, low je) for optimum Cs conditions on the plasma parameters at the BATMAN (Bavarian Test MAchine for Negative hydrogen ions) test facility is desirable in order to find key parameters for the operation of the source as well as to deepen the physical understanding. The most relevant source physics takes place in the extended boundary layer, which is the plasma layer with a thickness of several cm in front of the plasma grid: the production of H-, its transport through the plasma and its extraction, inevitably accompanied by the co-extraction of electrons. Hence, a link of the source performance with the plasma parameters in the extended boundary layer is expected. In order to characterize electron and negative hydrogen ion fluxes in the extended boundary layer, Cavity Ring-Down Spectroscopy and Langmuir probes have been applied for the measurement of the H- density and the determination of the plasma density, the plasma potential and the electron temperature, respectively. The plasma potential is of particular importance as it determines the sheath potential profile at the plasma grid: depending on the plasma grid bias relative to the plasma potential, a transition in the plasma sheath from an electron repelling to an electron attracting sheath takes place, influencing strongly the electron fraction of the bias current and thus the amount of co-extracted electrons. Dependencies of the source performance on the determined plasma parameters are presented for the comparison of two source pressures (0.6 Pa, 0.45 Pa) in hydrogen operation. The higher source pressure of 0.6 Pa is a standard point of operation at BATMAN with external magnets, whereas the lower pressure of 0.45 Pa is closer to the ITER requirements (p ≤ 0.3 Pa).

  16. Increasing plasma parameters using sheared flow stabilization of a Z-pinch

    Science.gov (United States)

    Shumlak, U.; Nelson, B. A.; Claveau, E. L.; Forbes, E. G.; Golingo, R. P.; Hughes, M. C.; Oberto, R. J.; Ross, M. P.; Weber, T. R.

    2017-05-01

    The ZaP and ZaP-HD Flow Z-pinch experiments at the University of Washington have successfully demonstrated that sheared plasma flows can be used as a stabilization mechanism over a range of parameters that has not previously been accessible to long-lived Z-pinch configurations. The stabilization is effective even when the plasma column is compressed to small radii, producing predicted increases in magnetic field and electron temperature. The flow shear value, extent, and duration are shown to be consistent with theoretical models of the plasma viscosity, which places a design constraint on the maximum axial length of a sheared flow stabilized Z-pinch. Measurements of the magnetic field topology indicate simultaneous azimuthal symmetry and axial uniformity along the entire 100 cm length of the Z-pinch plasma. Separate control of plasma acceleration and compression has increased the accessible plasma parameters and has generated stable plasmas with radii of 0.3 cm, as measured with a high resolution digital holographic interferometer. Compressing the plasma with higher pinch currents has produced high magnetic fields (8.5 T) and electron temperatures (1 keV) with an electron density of 2 ×1017 cm-3, while maintaining plasma stability for many Alfvén times (approximately 50 μs). The results suggest that sheared flow stabilization can be applied to extend Z-pinch plasma parameters to high energy densities.

  17. HPLC-UV determination of metformin in human plasma for application in pharmacokinetics and bioequivalence studies.

    Science.gov (United States)

    Porta, Valentina; Schramm, Simone Grigoleto; Kano, Eunice Kazue; Koono, Eunice Emiko; Armando, Yara Popst; Fukuda, Kazuo; Serra, Cristina Helena Dos Reis

    2008-01-07

    In this study, a simple, rapid and sensitive HPLC method with UV detection is described for determination of metformin in plasma samples from bioequivalence assays. Sample preparation was accomplished through protein precipitation with acetonitrile and chromatographic separation was performed on a reversed-phase phenyl column at 40 degrees C. Mobile phase consisted of a mixture of phosphate buffer and acetonitrile at flow rate of 1.0 ml/min. Wavelength was set at 236 nm. The method was applied to a bioequivalence study of two drug products containing metformin, and allowed determination of metformin at low concentrations with a higher throughput than previously described methods.

  18. Clinical pharmacokinetics of melatonin

    DEFF Research Database (Denmark)

    Harpsøe, Nathja Groth; Andersen, Lars Peter Holst; Gögenur, Ismail

    2015-01-01

    was performed in PubMed and Embase databases. The pharmacokinetic variables included maximal plasma/serum concentration (Cmax), time to maximal plasma/serum concentration (Tmax), elimination half-life (T1/2), area-under-the-curve plasma/serum concentrations (AUC), clearance (Cl), volume of distribution (VD......) and 1602 L (4 mg, oral). Bioavailability of oral melatonin ranged from 9 to 33%. Pharmacokinetics was affected by age, caffeine, smoking, oral contraceptives, feeding status, and fluvoxamine. Critically ill patients displayed accelerated absorption and compromised elimination. CONCLUSIONS: Despite...

  19. Langmuir probe Diagnostic for local parameter measurement in Magnetized Plasma using LabVIEW

    Directory of Open Access Journals (Sweden)

    Bijal Vara

    2014-03-01

    Full Text Available In recent years, plasma technology is used by Semiconductor, thin film industries for deposit layers, etching process and surface modification. So it is necessary to understanding internal plasma parameter. Langmuir probe is one of the simplest techniques which is used to measure wide range of plasma parameter like plasma potential, floating potential, electron temperature, electron energy distribution function (EEDF etc. Langmuir current voltage characteristic is obtained by varying bias voltage of the probe. LabVIEW is most powerful Microsoft window compatible software which is used to immediate data acquisition and analysis. In this paper describes analysis of Langmuir data using LabVIEW software which automatically measure I-V Plasma probe Characteristics and obtain EEDF of plasma.

  20. Simultaneous quantification of cefpodoxime proxetil and clavulanic acid in human plasma by LC-MS using solid phase extraction with application to pharmacokinetic studies.

    Science.gov (United States)

    Dubala, Anil; Nagarajan, Janaki Sankarachari Krishnan; Vimal, Chandran Sathish; George, Renjith

    2013-03-15

    A simple, rapid and selective high performance liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (HPLC-APCI-MS) method was developed and validated for the simultaneous estimation of cefpodoxime proxetil (CDPX) and clavulanic acid (CA) in human plasma. Extraction of samples was done by solid phase extraction technique (SPE) and chloramphenicol used as internal standard. Chromatographic separation was carried out on a reverse phase Princeton SPHER C18 (150mm×4mm i.d., 5μm) column using mixture of methanol: acetonitrile: 2mM ammonium acetate (25:25:50, v/v, pH 3.5) at 0.8mL/min flow rate. Detection was performed on a single quadrupole MS by selected ion monitoring (SIM) mode via APCI source. The calibration curve was linear within the concentration range, 0.04-4.4μg/mL and 0.1-10.0μg/mL for CDPX and CA respectively. Pharmacokinetic parameters of tablet (CDPX 200mg, CA 125mg) were evaluated. Cmax, Tmax, T1/2, elimination rate constant (Kel), AUC0-t, and AUC0-∞ of tablet were 2.13±0.06μg/mL, 2h, 3.05±0.15h, 0.24±0.37h(-1), 6.81±0.14μg h/mL and 7.72±0.23μg h/mL respectively for cefpodoxime (CP), 5.34±0.28μg/mL, 2h, 2.73±0.25h, 0.26±0.31h(-1), 15.37±0.16μg h/mL and 16.59±0.53μg h/mL respectively for CA.

  1. Metabolism and plasma pharmacokinetics of isoorientin, a natural active ingredient, in Sprague-Dawley male rats after oral and intravenous administration.

    Science.gov (United States)

    Shi, Peiying; Lin, Xinhua; Yao, Hong

    2015-01-01

    1. Several pharmacological effects have been revealed on isoorientin, suggesting its potential medicinal prospects. The metabolic and plasma pharmacokinetic profiles of isoorientin were investigated in rats. 2. For intra-gastric gavage, parent drug and three metabolites were detected in urine and feces by HPLC-MS/MS, but only one metabolite was found in plasma and identified as isoorientin 3'- or 4'-O-sulfate (M1) according to MS and UV absorbance spectra. 3. After a single i.v. administration of isoorientin (5, 10, or 15 mg/kg B.W.) in rats, linear pharmacokinetic property was observed with favorable terminal half-lives (1.67 ± 1.32-2.07 ± 0.50 h). After a single p.o. administration of isoorientin (150 mg/kg B.W.) in rats, plasma isoorientin concentration was low, but the concentration of M1 was comparatively high. Low systemic exposure of oral isoorientin in rats could result from its low aqueous solubility and extensive first-pass metabolism, and plasma concentration of M1 can be used as a biomarker of isoorientin intake. Isoorientin showed low oral bioavailability (8.98 ± 1.07%), and had about 6% or 45% dose recovery in urine or feces, respectively, 72 h after intra-gastric gavage. 4. These studies are the first to describe the pharmacokinetics of isoorientin via i.v. or p.o. dosing, providing important information for understanding its process in vivo.

  2. Determination of Some Biochemical Parameters in the Seminal Plasma of German Shepherd Dogs

    OpenAIRE

    GÜNAY, Ülgen

    2003-01-01

    In this study, we aimed to determine the levels of some biochemical parameters in the seminal plasma of German Shepherd dogs. Seven German Shepherd dogs were used as materials. A total of 35 ejaculates, five from each dog, were collected. The seminal plasma of each ejaculate was separated by centrifugation at 5000 rpm for 10 min. Biochemical analyses of the seminal plasma were performed. In conclusion, the average concentrations of total protein, calcium, phosphorus, magnesium, sodium and pot...

  3. Plasma pharmacokinetics, tissue disposition, excretion and metabolism of vinleucinol in mice as determined by high-performance liquid chromatography.

    Science.gov (United States)

    van Tellingen, O; Sonneveldt, A L; Beijnen, J H; Nooijen, W J; Kettenes-van den Bosch, J J; Versluis, C; Bult, A

    1994-01-01

    We investigated the pharmacokinetics of the experimental semisynthetic vinca alkaloid vinleucinol (VileE; O4-deacetyl-3-de(methoxycarbonyl)-3-[[[1-ethoxycarbonyl-2- methylbutyl]amino]carbonyl]-vincaleukoblastine). The study was performed in male FVB mice receiving 10.5 mg/kg VileE i.v. or p.o. Plasma, urine, faeces and tissue samples were analysed by a selective method based on ion-exchange normal-phase high-performance liquid chromatography (HPLC) with fluorescence detection and liquid-liquid extraction for sample clean-up. Apart from the parent drug, two other metabolic compounds were detected. One of these metabolites is vinleucinol acid (VileA; O4-deacetyl-3-de(methoxycarbonyl)-3-[[[1-carboxyl-2- methylbutyl]amino]carbonyl]-vincaleukoblastine), which possesses no cytotoxic activity. The structure proposed for the second metabolite (VileX) was based on tandem mass spectrometry (MS-MS) and infrared (IR) spectroscopy data. Metabolization of VileE to VileX must occur in the amino acid moiety of the molecule, with a (beta- or gamma-) lactone ring being formed after oxidation of the (beta- or gamma) carbon of the amino acid. VileX is a major metabolite, which is excreted in faeces and urine after i.v. administration and accounting for up to 23% of the administered dose. The activity of VileX against cultured L1210 cells is four times that of the parent drug VileE and comparable with that of vinblastine (VBL). At 48 h after administration of VileE, the concentration of VileX exceeds that of the parent drug in many tissues. These findings indicate that the metabolite VileX may be at least largely responsible for the activity observed against xenografts in mice after administration of the parent drug, VileE.

  4. Comparison of pharmacokinetic behavior of two iridoid glycosides in rat plasma after oral administration of crude Cornus officinals and its jiuzhipin by high performance liquid chromatography triple quadrupole mass spectrometry combined with multiple reactions monitoring mode

    OpenAIRE

    Xiaocheng Chen; Gang Cao; Jianping Jiang

    2014-01-01

    Objective: The present study examined the pharmacokinetic profiles of two iridoid glycosides named morroniside and loganin in rat plasma after oral administration of crude and processed Cornus officinals. Materials and Methods: A rapid, selective and specific high-performance liquid chromatography/electrospray ionization tandem mass spectrometry with multiple reactions monitoring mode was developed to simultaneously investigate the pharmacokinetic profiles of morroniside and loganin in rat pl...

  5. Simultaneous determination of ten flavonoids of crude and wine-processed Radix Scutellariae aqueous extracts in rat plasma by UPLC-ESI-MS/MS and its application to a comparative pharmacokinetic study.

    Science.gov (United States)

    Cui, Xiao-Bing; Qian, Xiao-Cui; Huang, Ping; Zhang, Yong-Xin; Li, Jun-Song; Yang, Guang-Ming; Cai, Bao-Chang

    2015-07-01

    Radix Scutellariae (RS) is a herbal medicine with various pharmacological activities to treat inflammation, respiratory and gastrointestinal infections, etc. In this study, a rapid, sensitive and selective UPLC-ESI-MS/MS method was developed for simultaneous determination of 10 flavonoids - scutellarin, scutellarein, chrysin, wogonin, baicalein, apigenin, wogonoside, oroxylin A-7-O-glucuronide, oroxylin A and baicalin - from RS aqueous extracts in rat plasma with propyl paraben as internal standard (IS). Chromatographic separation was achieved on a C18 column using gradient elution with the mobile phase consisting of methanol and water (containing 0.1% formic acid) at a flow rate of 0.2 mL/min. The detection was performed in multiple reaction monitoring mode using electrospray ionization in negative mode. The validated method showed good linearity over a wide concentration range (r >0.9935). The intra- and interday assay variabilities were extraction recovery ranged from 71.2 to 89.7% for each analyte and IS. This method was successfully applied to pharmacokinetic comparision after oral administration of crude and wine-processed RS aqueous extracts. There were significant differences in some pharmacokinetic parameters of most analytes between crude and wine-processed RS. This suggested that wine-processing exerted effects absorption of most flavonoids. © 2014 The Authors. Biomedical Chromatography published by John Wiley & Sons Ltd.

  6. EFFECT OF PLASMA CUTTING PARAMETERS UPON SHAPES OF BEARING CURVE OF C45 STEEL SURFACE

    Directory of Open Access Journals (Sweden)

    Agnieszka Skoczylas

    2015-08-01

    Full Text Available The article presents the results of studies on the effect of plasma cutting technological parameters upon the shape of bearing curves and the parameters of the curve. The topography of surface formed by plasma cutting were analyzed. For measuring surface roughness and determining the bearing curve the appliance T8000 RC120 – 400 by Hommel-Etamic was used together with software.

  7. Alteration of Lysophosphatidylcholine-Related Metabolic Parameters in the Plasma of Mice with Experimental Sepsis.

    Science.gov (United States)

    Ahn, Won-Gyun; Jung, Jun-Sub; Kwon, Hyeok Yil; Song, Dong-Keun

    2017-04-01

    Plasma concentration of lysophosphatidylcholine (LPC) was reported to decrease in patients with sepsis. However, the mechanisms of sepsis-induced decrease in plasma LPC levels are not currently well known. In mice subjected to cecal ligation and puncture (CLP), a model of polymicrobial peritoneal sepsis, we examined alterations in LPC-related metabolic parameters in plasma, i.e., the plasma concentration of LPC-related substances (i.e., phosphatidylcholine (PC) and lysophosphatidic acid (LPA)), and activities or levels in the plasma of some enzymes that can be involved in the regulation of plasma LPC concentration (i.e., secretory phospholipase A2 (sPLA2), lecithin:cholesterol acyltransferase (LCAT), acyl-CoA:lysophosphatidylcholine acyltransferase (LPCAT), and autotaxin (ATX)), as well as plasma albumin concentration. We found that levels of LPC and albumin and enzyme activities of LCAT, ATX, and sPLA2 were decreased, whereas levels of PC, LPA, and LPCAT1-3 were increased in the plasma of mice subjected to CLP. Bacterial peritonitis led to alterations in all the measured LPC-related metabolic parameters in the plasma, which could potentially contribute to sepsis-induced decrease in plasma LPC levels. These findings could lead to the novel biomarkers of sepsis.

  8. Analyses of plasma parameter profiles in JT-60U

    Energy Technology Data Exchange (ETDEWEB)

    Shirai, Hiroshi; Shimizu, Katsuhiro; Hayashi, Nobuhiko [Japan Atomic Energy Research Inst., Naka, Ibaraki (Japan). Naka Fusion Research Establishment; Itakura, Hirofumi; Takase, Keizou [CSK Co. Ltd., Tokyo (Japan)

    2001-01-01

    The methods how diagnostics data are treated as the surface quantity of magnetic surface and processed to the profile data in the JT-60U plasmas are summarized. The MHD equilibrium obtained by solving Grad-Shafranov equation on the MHD equilibrium calculation and registration software FBEQU are saved shot by shot as a database. Various experimental plasma data measured at various geometrical positions on JT-60 are mapped onto the MHD equilibrium and treated as functions of the volume averaged minor radius {rho} on the experimental data time slice monitoring software SLICE. Experimental data are integrated and edited on SLICE. The experimental data measured as the line integral values are transformed by Able inversion. The mapped data are fitted to a functional form and saved to the profile database MAP-DB. SLICE can also read data from MAP-DB and redisplay and transform them. In addition, SLICE can generate the profile data TOKRD as run data for orbit following Monte-Carlo (OFMC) code, analyzer for current drive consistent with MHD equilibrium (ACCOME) code and tokamak predictive and interpretive code system (TOPICS). (author)

  9. LC-MS/MS determination of cinacalcet enantiomers in rat plasma on Chirobiotic V column in polar ionic mode: application to a pharmacokinetic study.

    Science.gov (United States)

    Ramisetti, Nageswara Rao; Bompelli, Sravan

    2014-12-01

    A simple and selective polar ionic liquid chromatography-tandem mass spectrometric method for separation and determination of cinacalcet enantiomers in rat plasma was developed and validated. The chromatographic separation was accomplished on a Chirobiotic V column packed with vancomycin as a chiral stationary phase using 2.5 mm ammonium formate in 100% methanol as a mobile phase in an isocratic mode of elution at a flow rate of 1.0 mL/min. The analytes were extracted from rat plasma by precipitating the proteins with acetonitrile. The developed method exhibited a linear dynamic range over 0.5-500 ng/mL in rat plasma for both enantiomers. The method was successfully applied to study the pharmacokinetics after a single dose by oral administration of 10 mg/kg of cinacalcet enantiomers to healthy male Wistar rats.

  10. Plasma pharmacokinetics and milk residues of flunixin and 5-hydroxy flunixin following different routes of administration in dairy cattle.

    Science.gov (United States)

    Kissell, L W; Smith, G W; Leavens, T L; Baynes, R E; Wu, H; Riviere, J E

    2012-12-01

    The objective of this study was to determine if the plasma pharmacokinetics and milk elimination of flunixin (FLU) and 5-hydroxy flunixin (5OH) differ following intramuscular and subcutaneous injection of FLU compared with intravenous injection. Twelve lactating Holstein cows were used in a randomized crossover design study. Cows were organized into 2 groups based on milk production (30 kg of milk/d). All cattle were administered 2 doses of 1.1mg of FLU/kg at 12-h intervals by intravenous, intramuscular, and subcutaneous injections. The washout period between routes of administration was 7d. Blood samples were collected from the jugular vein before FLU administration and at various time points up to 36 h after the first dose of FLU. Composite milk samples were collected before FLU administration and twice daily for 5d after the first dose of FLU. Samples were analyzed by ultra-HPLC with mass spectrometric detection. For FLU plasma samples, a difference in terminal half-life was observed among routes of administration. Harmonic mean terminal half-lives for FLU were 3.42, 4.48, and 5.39 h for intravenous, intramuscular, and subcutaneous injection, respectively. The mean bioavailability following intramuscular and subcutaneous dosing was 84.5 and 104.2%, respectively. The decrease in 5OH milk concentration versus time after last dose was analyzed with the nonlinear mixed effects modeling approach and indicated that both the route of administration and rate of milk production were significant covariates. The number of milk samples greater than the tolerance limit for each route of administration was also compared at each time point for statistical significance. Forty-eight hours after the first dose, 5OH milk concentrations were undetectable in all intravenously injected cows; however, one intramuscularly injected and one subcutaneously injected cow had measurable concentrations. These cows had 5OH concentrations above the tolerance limit at the 36-h withdrawal time

  11. Determination of Acyclovir in Human Plasma Samples by HPLC Method with UV Detection: Application to Single-Dose Pharmacokinetic Study

    Directory of Open Access Journals (Sweden)

    Dragica Zendelovska

    2015-03-01

    CONCLUSION: Good precision, accuracy, simplicity, sensitivity and shorter time of analysis of the method makes it particularly useful for processing of multiple samples in a limited period of time for pharmacokinetic study of acyclovir.

  12. Effect of ketoprofen and indomethacin on methotrexate pharmacokinetics in mice plasma and tumor tissues.

    Science.gov (United States)

    Elmorsi, Yasmine M; El-Haggar, Sahar M; Ibrahim, Osama M; Mabrouk, Mokhtar M

    2013-03-01

    Methotrexate (MTX) has been used in combination with nonsteroidal anti-inflammatory drugs in the treatment of inflammatory diseases as well as malignancies. Severe adverse effects with this combination may occur, usually resulting from inhibition of renal transporters. Solid Ehrlich carcinoma was experimentally induced by implantation of Ehrlich ascites Carcinoma cells subcutaneously into the thigh of mice, and after 30 days, mice were divided into three groups: Group I that served as control group received MTX (50 mg/kg, i.p.); Group II received ketoprofen (100 mg/kg, i.p.) and then after half an hour received MTX (50 mg/kg, i.p.); Group III received indomethacin (10 mg/kg, i.p.) and then after half an hour received MTX (50 mg/kg, i.p.). Plasma and tissue samples were collected at different time points and then MTX concentrations were determined by HPLC. The injection of ketoprofen or indomethacin before MTX injection resulted in significant increase in the AUC and CPmax of MTX (p ketoprofen. The study showed that administration of ketoprofen or indomethacin prior to MTX caused significant decrease in MTX elimination and significant increase in MTX extent of absorption which may lead to severe adverse effects if coadministered in human.

  13. Potentials of polymeric nanoparticle as drug carrier for cancer therapy: with a special reference to pharmacokinetic parameters.

    Science.gov (United States)

    Mukherjee, Biswajit; Das, Surajit; Chakraborty, Samrat; Satapathy, Bhabani Sankar; Das, Pranab Jyoti; Mondal, Laboni; Hossain, Chowdhury Mobaswar; Dey, Niladri Shekhar; Chaudhury, Anumita

    2014-01-01

    Nanomaterials have made a significant impact on cancer therapeutics and an emergence of polymeric nanoparticle provides a unique platform for delivery of drug molecules of diverse nature. Nanoparticles can be targeted at the tumor cells due to enhanced permeability and retention effect. Moreover, nanoparticles can be grafted by various ligands on their surface to target the specific receptors overexpressed by cancer cells or angiogenic endothelial cells. These approaches ultimately result in longer circulation half-lives, improved drug pharmacokinetics, reduced side effects of therapeutically active substances and overcoming cancer chemo-resistance thereby enhancing the therapeutic efficacy of the treatment. This review article summarizes the recent efforts in cancer nanochemotherapeutics using polymeric nanoparticles with a special reference to their pharmacokinetic and biodistribution profiles, their role in reversing multidrug resistance in cancer and strategies of tumor targeting with them, along with the challenges in the field.

  14. Downstream plasma parameters in laminar shocks from ion kinetics

    Science.gov (United States)

    Gedalin, M.

    2016-10-01

    Ion dynamics in oblique shocks is governed by the macroscopic electric and magnetic fields of the shock front. In laminar shocks, these fields are time-independent and depend only on the coordinate along the shock normal. The shock ramp is narrow and the ion motion across the shock is manifestly non-adiabatic. The ion distribution just behind the ramp is significantly non-gyrotropic. Gyrotropy is achieved well behind the ramp mainly due to the gyrophase mixing. The asymptotic values of the ion density and temperature are determined by the eventual collisionless relaxation of the gyrating ion distribution. Given a distribution at the downstream edge of the ramp, the moments of the distribution after gyrophase mixing are derived using proper spatial averaging. The obtained expressions can be used for independent determination of the downstream plasma state and implementation in Rankine-Hugoniot relations.

  15. Influence of direct current plasma magnetron sputtering parameters on the material characteristics of polycrystalline copper films

    Energy Technology Data Exchange (ETDEWEB)

    Chan, K.-Y. [Thin Film Laboratory, Faculty of Engineering, Multimedia University, Jalan Multimedia, 63100 Cyberjaya, Selangor (Malaysia)], E-mail: k.y.chan@fz-juelich.de; Luo, P.-Q.; Zhou, Z.-B. [Department of Physics, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240 Shanghai (China); Tou, T.-Y.; Teo, B.-S. [Thin Film Laboratory, Faculty of Engineering, Multimedia University, Jalan Multimedia, 63100 Cyberjaya, Selangor (Malaysia)

    2009-03-01

    Physical vapor processes using glow plasma discharge are widely employed in microelectronic industry. In particular magnetron sputtering is a major technique employed for the coating of thin films. This paper addresses the influence of direct current (DC) plasma magnetron sputtering parameters on the material characteristics of polycrystalline copper (Cu) thin films coated on silicon substrates. The influence of the sputtering parameters including DC plasma power and argon working gas pressure on the electrical and structural properties of the thin Cu films was investigated by means of surface profilometer, four-point probe and atomic force microscopy.

  16. Simultaneous Determination of Purpurin, Munjistin and Mollugin in Rat Plasma by Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry: Application to a Pharmacokinetic Study after Oral Administration of Rubia cordifolia L. Extract

    Directory of Open Access Journals (Sweden)

    Mingjie Gao

    2016-06-01

    Full Text Available A specific, simple, sensitive Ultra High Performance Liquid Chromatography-tandem Mass Spectrometry (UHPLC-MS/MS method has been developed and validated for the simultaneous determination and pharmacokinetic study of purpurin, munjistin, and mollugin in rat plasma. Chromatographic separation was carried out using a C18 column (ACQUITY UPLC® HSS T3, 1.8 μm, 2.1 × 100 mm with gradient elution. The compounds were detected on a 6430 triple-quadrupole tandem MS with an electrospray ionization (ESI interface using multiple reaction monitoring (MRM in positive ionization mode. The samples were prepared by a liquid-liquid extraction (LLE method with ethyl acetate after being spiked with an internal standard (bifendate. The current UHPLC-MS/MS assay was validated for its linearity, intra-day and inter-day precisions, accuracy, extraction recovery, matrix effect and stability in different conditions. The method was linear for all analytes over the investigated range with all determined correlation coefficients exceeding 0.9900. The intra-day and inter-day precisions were in the range of 4.21% to 14.84%, and the relative errors of accuracies were in the range of −14.05% to 14.75%. The mean recoveries and matrix effects of purpurin, munjistin, and mollugin were higher than 78.87% and 92.56%, repectively. After oral administration of 0.82 g/kg of Rubia cordifolia extract, the maximum plasma concentrations (Cmax were 70.10 ± 11.78 ng/mL for purpurin, 26.09 ± 6.6 ng/mL for munjistin, and 52.10 ± 6.71 ng/mL for mollugin. The time for maximal concentration (Tmax was 1.61 ± 0.24 h for purpurin, 2.58 ± 0.19 h for munjistin, and 1.99 ± 0.21 h for mollugin. The established method was further applied to a pharmacokinetic study of purpurin, munjistin, and mollugin in rat plasma. It was concluded from the pharmacokinetic parameters that the three analytes showed a process of slow absorption and metabolism after oral administration of R. cordifolia extract to

  17. LC-MS/MS determination and comparative pharmacokinetics of strychnine, brucine and their metabolites in rat plasma after intragastric administration of each monomer and the total alkaloids from Semen Strychni.

    Science.gov (United States)

    Lin, Aihua; Su, Xiaochun; She, Dan; Qiu, Kuncheng; He, Qianmei; Liu, Yiming

    2016-01-01

    A rapid, specific and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the simultaneous determination of strychnine, brucine, strychnine N-oxide and brucine N-oxide in rat plasma. Plasma samples were pretreated via simple protein precipitation with methanol and ephedrine hydrochloride was used as internal standard. Chromatographic separation was carried out on an ZORBAX Eclipse XDB-C18 column (2.1×150mm, 3.5μm) by gradient elution with methanol and 10mM ammonium acetate (adjusted to pH 4.0 with formic acid). The quantification of the analytes was performed by mass spectrometry with TurboIonSpray ionization (ESI) inlet in the positive ion multiple reaction monitoring (MRM) mode. The results showed that the calibration curve was linear in the concentration range of 0.510∼306.3ngmL(-1) for strychnine, brucine and 0.102∼306.0ngmL(-1) for strychnine N-oxide and brucine N-oxide, respectively. The intra- and inter-day precisions were less than 14.9%, and the accuracy ranged from 89.4 to 113% at three QC levels for the 4 analytes. The validated method was successfully applied to the pharmacokinetic study of strychnine, brucine, strychnine N-oxide and brucine N-oxide in rat plasma after oral administration of each monomer and the total alkaloids from Semen Strychni. After single oral administration of the total alkaloids from Semen Strychni at 4 dose levels, Cmax, AUC0-t of strychnine and brucine increased and were proportional to the oral doses. In comparative pharmacokinetics studies, no significant difference was found between each monomer and the total strychnos alkaloids on the pharmacokinetic parameters such as Cmax and AUC. Mean Cmax and AUC of strychnine and brucine were slight increased in the monomer groups in comparison to the total strychnos alkaloids groups, which suggested that some other alkaloids in the Semen Strychni may decrease the absorption of strychnine and brucine in body. Copyright

  18. Estimation of tulathromycin depletion in plasma and milk after subcutaneous injection in lactating goats using a nonlinear mixed-effects pharmacokinetic modeling approach

    OpenAIRE

    Lin, Zhoumeng; Cuneo, Matthew; Rowe, Joan D.; Li, Mengjie; Tell, Lisa A; Allison, Shayna; Carlson, Jan; Riviere, Jim E.; Gehring, Ronette

    2016-01-01

    Background Extra-label use of tulathromycin in lactating goats is common and may cause violative residues in milk. The objective of this study was to develop a nonlinear mixed-effects pharmacokinetic (NLME-PK) model to estimate tulathromycin depletion in plasma and milk of lactating goats. Eight lactating goats received two subcutaneous injections of 2.5 mg/kg tulathromycin 7 days apart; blood and milk samples were analyzed for concentrations of tulathromycin and the common fragment of tulath...

  19. Population Pharmacokinetics of Intranasal Scopolamine

    Science.gov (United States)

    Wu, L.; Chow, D. S. L.; Putcha, L.

    2013-01-01

    Introduction: An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS).The bioavailability and pharmacokinetics (PK) was evaluated using data collected in Phase II IND protocols. We reported earlier statistically significant gender differences in PK parameters of INSCOP at a dose level of 0.4 mg. To identify covariates that influence PK parameters of INSCOP, we examined population covariates of INSCOP PK model for 0.4 mg dose. Methods: Plasma scopolamine concentrations versus time data were collected from 20 normal healthy human subjects (11 male/9 female) after a 0.4 mg dose. Phoenix NLME was employed for PK analysis of these data using gender, body weight and age as covariates for model selection. Model selection was based on a likelihood ratio test on the difference of criteria (-2LL). Statistical significance for base model building and individual covariate analysis was set at P less than 0.05{delta(-2LL)=3.84}. Results: A one-compartment pharmacokinetic model with first-order elimination best described INSCOP concentration ]time profiles. Inclusion of gender, body weight and age as covariates individually significantly reduced -2LL by the cut-off value of 3.84(P less than 0.05) when tested against the base model. After the forward stepwise selection and backward elimination steps, gender was selected to add to the final model which had significant influence on absorption rate constant (ka) and the volume of distribution (V) of INSCOP. Conclusion: A population pharmacokinetic model for INSCOP has been identified and gender was a significant contributing covariate for the final model. The volume of distribution and Ka were significantly higher in males than in females which confirm gender-dependent pharmacokinetics of scopolamine after administration of a 0.4 mg dose.

  20. Using UPLC-MS/MS for Characterization of Active Components in Extracts of Yupingfeng and Application to a Comparative Pharmacokinetic Study in Rat Plasma after Oral Administration

    Directory of Open Access Journals (Sweden)

    Meng-Qi Jia

    2017-05-01

    Full Text Available Yupingfeng (YPF, a famous traditional Chinese medicine, which contains a large array of compounds, has been effectually used in health protection. A two-dimensional liquid chromatography (2D-LC combined with quadrupole time-of-flight mass spectrometry (QTOF-MS method was firstly established to separate and identify chemical components in YPF. A total of 33 compounds were identified, including 15 constituents (flavonoids and saponins in Astragali radix; seven constituents (sesquiterpenoids and polysaccharide in Atractylodis rhizoma; and 11 constituents (chromone and coumarins in Saposhnikoviae radix. The corresponding fragmentation pathway of typical substances was investigated. Then, seven active constituents (astragaloside, calycosin, formononetin, cimicifugoside, 4-O-beta-d-glucosyl-5-O-methylvisamminol, sec-O-glucosylhamaudol, and atractylenolide II derived from three medicinal plants were chosen to further investigate the pharmacokinetic behavior of YPF formula using ultrahigh-performance liquid chromatography with triple quadrupole mass spectrometry system. The method was sensitive, accurate and reliable. We also used the area under the plasma concentration–time curve from zero to infinity (AUC0−∞ as weighting factor to make an integrated pharmacokinetic curve. Results show that the constituents of Saposhnikoviae radix have the best absorption and pharmacokinetic behavior and may play important role in leading to the changes of overall therapeutic effects of YPF. Further study is needed to confirm the association between them.

  1. Seminal plasma zinc level may be associated with the effect of cigarette smoking on sperm parameters.

    Science.gov (United States)

    Liu, R-Z; Gao, J-C; Zhang, H-G; Wang, R-X; Zhang, Z-H; Liu, X-Y

    2010-01-01

    The aim of this study was to investigate the effect of cigarette smoking on seminal plasma zinc levels and sperm parameters, and to examine the role of seminal plasma zinc. Semen samples from 79 non-smokers and 68 smokers were obtained. There was a significant decrease in seminal plasma zinc in smokers and a clear correlation between seminal plasma zinc levels and the extent of smoking. Sperm parameters (concentration, motility and morphology) among smokers were significantly lower in comparison to non-smokers. These parameters were also significantly decreased among smokers with abnormal zinc levels, while there was no significant difference between non-smokers with normal zinc and non-smokers with abnormal zinc levels. As previous studies have shown that seminal plasma zinc is associated with a decrease of anti-oxidant defences, seminal plasma zinc could be a contributor to the effects of cigarette smoking on sperm parameters. In conclusion, cigarette smoking can affect sperm parameters and this study may help towards providing a mechanistic explanation.

  2. A fully validated HPLC method for the simultaneous determination of acitretin and etretinate in plasma and its application to a pharmacokinetic study in healthy Korean subjects.

    Science.gov (United States)

    Park, H-D; Kim, H-K; Chun, M-R; Kim, J-W; Kim, D-W; Lee, J-H; Huh, W S; Youn, J-I; Kim, H-G; Kim, Y G; Kim, M-H; Lee, S-Y

    2009-07-01

    Acitretin is used for the treatment of psoriasis. The purpose of this study was to validate an HPLC method for the determination of acitretin and etretinate and to investigate the pharmacokinetic characteristics of acitretin in healthy Korean subjects. Plasma samples or calibrators were mixed with acetonitrile and retinyl acetate (internal standard). Butanol: acetonitrile (1:1 v/v) and K2HPO4 were added later. After vortexing, 30 microl of the supernatant was injected directly into the analytical column of an HPLC system. The samples were separated by C18 reversed phase HPLC and UV detection was performed at 350 nm. Various assay performances were evaluated. The linearity of acitretin and etretinate was adequate up to 500 ng/ml (R2 = 0.9937 for acitretin and R2 = 0.9923 for etretinate). The accuracy was 89.5 - 113.5% and the precision was satisfactory (within-run CV, 4.4 - 15.8%; between-run CV, 3.3 - 17.4%). The LLOQ was 2 ng/ml and the stability and specificity were satisfactory. However, after storage at room temperature for 24 h under light exposure, the concentrations of acitretin and etretinate decreased by 26.0 - 66.5%. Extraction recovery was 75.1 - 91.5%. Nine healthy Korean subjects were evaluated to study the pharmacokinetics of acitretin. A single oral dose of 30 mg acitretin (Neotigason, Roche Pharmaceuticals) was given to all volunteers. The mean +/- SD pharmacokinetics of acitretin in Koreans were as follows: Cmax 148.7 +/- 93.0 ng/ml, tmax 3.2 +/- 1.3 h, t1/2 81.2 +/- 26.5 h, and AUClast 2641.9 +/- 1274.8 ng h/ml. A simple HPLC method for the simultaneous determination of acitretin and etretinate was validated, and the pharmacokinetic characteristics of acitretin in the Korean population were investigated.

  3. Determination of 6258-70, a new semi-synthetic taxane, in rat plasma and tissues: Application to the pharmacokinetics and tissue distribution study

    Directory of Open Access Journals (Sweden)

    Simin Zhao

    2016-08-01

    Full Text Available Cancer is the leading cause of death all over the world. Among the chemotherapy drugs, taxanes play an important role in cancer treatment. 6258-70 is a new semi-synthetic taxane which has a broad spectrum of antitumor activity. A fast and reliable high performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS method was developed for quantification of 6258-70 in rat plasma and tissues in this paper. After extraction by liquid-liquid extraction method with methyl tert-butyl ether, the samples were separated on a Kinetex C18 column (50 mm×2.1 mm, 2.6 µm, Phenomenex, USA within 3 min. The method was fully validated with the matrix effect between 87.7% and 99.5% and the recovery ranging from 80.3% to 90.1%. The intra- and inter-day precisions were less than 9.5% and the accuracy ranged from −3.8% to 6.5%. The reliable method was successfully applied to the pharmacokinetics and tissue distribution studies of 6258-70 after intravenous administration in rats. The pharmacokinetic results indicated that the pharmacokinetic behavior of 6258-70 in rats was in accordance with linear features within tested dosage of 1 to 4 mg/kg, and there was no significant difference between the two genders. The tissue distribution study showed that 6258-70 had an effective penetration, spread widely and rapidly and could cross blood-brain barrier. The results of pharmacokinetics and tissue distribution may provide a guide for future study.

  4. Effects of cigarette smoking on hemorheologic parameters, plasma osmolality and lung function.

    Science.gov (United States)

    Ergun, Dilek Duzgun; Karis, Denizhan; Alkan, Fatma Ates; Cakmak, Gulfidan; Yenigun, Mustafa; Ercan, Meltem

    2016-10-05

    Cigarette smoking deteriorates human health via vascular disorders, cancer and especially respiratory diseases. The aim of this study is to investigate effects of cigarette smoking on hemorheologic parameters, plasma osmolality and lung function in individuals without diagnosis of chronic obstructive pulmonary disease (COPD). Patients diagnosed without COPD utilizing respiratory function test were enrolled in the study with three groups, ex-smokers (n = 21), current-smokers (n = 35) and never-smokers (n = 43). Hemorheologic parameters and plasma osmolality were measured in hemorheology laboratory. SPSS 17.0 was used for statistical analysis. Blood and plasma viscosity, fibrinogen and hematocrit levels, mean corpuscular volume and mean corpuscular hemoglobin concentration were significantly elevated in ex-smokers and current-smokers compared to never-smokers. The standardized red blood cell deformability and oxygen delivery index and lung function were statistically lower in current-smokers than never-smokers. Pulmonary blood flow rate was statistically lower in current-smokers and ex-smokers than never-smokers. Plasma osmolality was statistically significantly higher in ex-smokers and current-smokers than never-smokers. Our findings clearly show that cigarette smoking has severe effects on hemorheologic parameters, plasma osmolality and lung function even in individuals without COPD. Blood and plasma viscosity with plasma osmolality might be useful markers to detect early hemorheologic-hemodynamic alterations in cigarette smokers.

  5. Validated LC-MS/MS method for simultaneous determination of SIM and its acid form in human plasma and cell lysate: Pharmacokinetic application%Validated LC-MS/MS method for simultaneous determination of SIM and its acid form in human plasma and cell lysate: Pharmacokinetic application

    Institute of Scientific and Technical Information of China (English)

    Tamer A. Ahmed; Jamie Horn; John Hayslip; Markos Leggas

    2012-01-01

    Simvastatin (SIM) is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor widely used in hyperlipidemia therapy. SIM has recently been studied for its anticancer activity at doses higher than those used for the hyperlipidemia therapy. This prompted us to study the pharmacokinetics of high-dose SIM in cancer patients. For this purpose, an LC-MS/MS method was developed to measure SIM and its acid form (SIMA) in plasma and peripheral blood mononuclear cells (PBMCs) obtained from patients. Chromatographic analyte separation was carried out on a reverse-phase column using 75:25 (% v/v) acetonitrile:ammonium acetate (0.1 M, pH 5.0) mobile phase. Detection was performed on a triple quadrupole mass spectrometer, equipped with a turbo ion spray source and operated in positive ionization mode. The assay was linear over a range 2.5-500 ng/mL for SIM and 5-500 ng/mL for SIMA in plasma and 2.5-250 ng/mL for SIM and 5-250 ng/mL for SIMA in cell lysate. Recovery was 〉 58% for SIM and 〉 75% for SIMA in both plasma and cell lysate. SIM and SIMA were stable in plasma, cell lysate and the reconstitution solution. This method was successfully applied for the determination of SIM and SIMA in plasma and PBMCs samples collected in the pharmacokinetic study of high-dose SIM in cancer patients.

  6. Simultaneous quantification of chrysophanol and physcion in rat plasma by ultra fast liquid chromatography-tandem mass spectrometry and application of the technique to comparative pharmacokinetic studies of Radix et Rhei Rhizoma extract alone and Dahuang Fuzi Decoction.

    Science.gov (United States)

    Liu, Xiao; Li, Huan; Wu, Li; Xing, Jiangwa; Poh, Yanhong; Cai, Hao; Cai, Bao Chang

    2015-02-01

    Most herbal medicines are prescribed in combination based on the theory of TCM to obtain synergistic effects or diminish the possible adverse reactions. Compatibility refers to the combination of two or more herbs based on the clinical settings and the properties of herbs. Chrysophanol and physcion are the main effective compounds in Radix et Rhizoma Rhei and Dahuang Fuzi Decoction which is the combination of Radix et Rhizoma Rhei, Radix Aconiti Lateralis Praeparata and Radix et Rhizoma Asari. However, chrysophanol and physcion are difficult to detect in vivo because of their low concentration and interference from endogenous compounds. The aim of this study is to develop a rapid, specific and sensitive ultra high performance liquid chromatography-triple quadrupole tandem mass method to simultaneously quantify chrysophanol and physcion in rat plasma, in order to better understand the pharmacokinetics and compatibility mechanism of Dahuang Fuzi Decoction for the first time. Multiple reaction monitoring (MRM) mode was applied for the quantitation at [M-H](-)m/z 253.0→m/z 225.1 for chrysophanol, [M-H](-) for m/z 283.1→m/z 240.0 physcion and [M-H](-)m/z 239.0→m/z 211.0 for IS. The analytes were separated on an Agilent Eclipse plus C18 column (100mm×2.1mm, 1.8μm) column within a total running time of 6.5min using a mixture of 3mM ammonium acetate in water and methanol (95:5, v/v) with a time program flow gradient according to the "plus gradient chromatography" theory. The inclusion of the ammonium acetate in the UFLC mobile phase dramatically improved the detection limit of the tested compounds and decreased the interference by matrix effects, which have been referred to as "LC-electrolyte effects". Finally, we demonstrated the application of a validated method in a comparative pharmacokinetic study of rats receiving an oral dose of Dahuang Fuzi Decoction or Radix et Rhei Rhizoma, the monarch drug in the prescription. Pharmacokinetic parameters showed

  7. Automatic measurements of plasma parameters in the PUPR mirror and cusp plasma machine

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez, S; Colmenares, F; Gonzalez-Lizardo, A; Leal-Quiros, E [Plasma Engineering Laboratory, Polytechnic University of Puerto Rico, San Juan, PR 00918 (Puerto Rico)

    2008-10-15

    This paper presents an ongoing effort to develop an automatic measurement system for plasma diagnostics at the Plasma Engineering Laboratory of the Polytechnic University of Puerto Rico (PUPR), along with an example of its operation. The system is intended to be used with electrostatic probes such as single and double Langmuir probes, emissive probes, ion and electron energy analyzers, etc. The automatic measurement system includes automatic positioning of the probes inside the plasma chamber, automatic voltage sweep of the probes for each position, and automatic analysis of the probe I-V characteristic. The results of measurements obtained by using this automatic measurement system during a particular experiment are shown and compared with a traditional method with satisfactory results.

  8. Validated LC-MS/MS method for the simultaneous determination of chlorambucil and its prodrug in mouse plasma and brain, and application to pharmacokinetics.

    Science.gov (United States)

    Wang, XinYi; Zhang, Quan; Lin, Qing; Zhang, Yue; Zhang, Zhi-Rong

    2014-10-01

    A simple, sensitive and rapid LC-MS/MS method was developed and validated for the simultaneous determination of chlorambucil (CHL) and the prodrug of chlorambucil (CHLS) in mouse plasma and brain tissue. Detection was performed on a Diamonsil ODS chromatography column using gradient elution with a mobile phase of 0.2% aqueous formic acid and acetonitrile. Mass spectrometry was carried out in multiple reaction monitoring mode using a positive electrospray ionization interface. Good linearity was found for CHLS and CHL in plasma and brain tissue in different linear ranges (r>0.9996). Intra-day and inter-day precision was within 9.11% and accuracy was not more than 11.07%. The validated method was successfully applied to the pharmacokinetic study of CHLS and CHL in mice after intravenous administration. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. A validated high-performance liquid chromatographic method for the determination of glibenclamide in human plasma and its application to pharmacokinetic studies.

    Science.gov (United States)

    Niopas, Ioannis; Daftsios, Athanasios C

    2002-05-15

    Glibenclamide is a potent second generation oral sulfonylurea antidiabetic agent widely used for the treatment of type II diabetes melitus. A rapid, sensitive, precise, accurate and specific HPLC assay for the determination of glibenclamide in human plasma was developed and validated. After addition of flufenamic acid as internal standard, the analytes were isolated from human plasma by liquid-liquid extraction. The method was linear in the 10-400 ng/ml concentration range (r > 0.999). Recovery for glibenclamide was greater than 91.5% and for internal standard was 93.5%. Within-day and between-day precision, expressed as the relative standard deviation (RSD%), ranged from 1.4 to 5.9% and 5.8 to 6.6%, respectively. Assay accuracy was better than 93.4%. The assay was used to estimate the pharmacokinetics of glibenclamide after oral administration of a 5 mg tablet of glibenclamide to 18 healthy volunteers.

  10. Simultaneous determination and pharmacokinetic study of four phenolic acids in rat plasma using UFLC-MS/MS after intravenous administration of salvianolic acid for injection.

    Science.gov (United States)

    Xie, Xiuman; Miao, Jingzhuo; Sun, Wanyang; Huang, Jingyi; Li, Dongxiang; Li, Shuming; Tong, Ling; Sun, Guoxiang

    2017-02-05

    A simple, sensitive and selective ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method was established for simultaneous determination and pharmacokinetic study of rosmarinic acid (RA), salvianolic acid D (Sal D), lithospermic acid (LA) and salvianolic acid B (Sal B) in rat plasma after intravenous administration of salvianolic acid for injection (SAFI). Three doses of administration, containing 14, 28 and 56mg/kg, were investigated in this study. Plasma samples were pretreated using protein precipitation (PP) with pre-cooled acetonitrile. Chromatographic separation was achieved on a CORTECS™ UPLC C18 column (1.6μm, 2.1×100mm) with a mobile phase composed of 0.1% formic acid aqueous (V/V) and 0.1% formic acid acetonitrile (V/V). Analytes were detected using electrospray ionization (ESI) source in negative ionization mode and quantified in multiple reaction monitoring (MRM) mode. The validated method is stable and reliable. No significant difference of half lives (t1/2) of four analytes at three doses was observed. Area under the curve (AUC0-∞) and peak concentration (Cmax) of the four analytes demonstrated a linear increase in across the doses with the linear correlation r of each analyte at three doses were greater than 0.95. It indicated that the pharmacokinetic behavior of SAFI is positively related to dose at the range of 14-56mg/kg.

  11. A rapid and sensitive UHPLC-MS/MS assay for the determination of trelagliptin in rat plasma and its application to a pharmacokinetic study.

    Science.gov (United States)

    Hu, Xiao-Xia; Lan, Tian; Chen, Zhe; Yang, Cheng-Cheng; Tang, Peng-Fei; Yuan, Ling-Jing; Hu, Guo-Xin; Cai, Jian-Ping

    2016-10-15

    This study aims to develop and validate a simple, rapid and sensitive ultra-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method for exploring pharmacokinetic characteristics of trelagliptin. Protein precipitation by acetonitrile was used to prepare plasma sample. A RRHD Eclipse Plus C18 (2.1×50mm, 1.8μ) column with gradient mobile phase (containing acetonitrile and 0.1% formic acid) help to achieve the separation of trelagliptin and carbamazepine (IS) with high selectivity. Detection of target fragment ions m/z 358.2→133.9 for trelagliptin, and m/z 237.1→194.0 for IS was performed in positive-ion electrospray ionization mass spectrometry by multiple reaction monitoring. Linear calibration plots were achieved in the range of 5-4000ng/mL for trelagliptin (R(2)=0.999) in rat plasma. The recovery of trelagliptin ranged from 87.8% to 93.7%. The method was showed to be accurate, precise and stable. No obvious matrix effect was found. It has been fully validated and successfully applied to pharmacokinetic study of trelagliptin.

  12. LC-MS determination and pharmacokinetic studies of paeonol in rat plasma after administration of different compatibility of Su-Xiao-Xin-Tong prescriptions.

    Science.gov (United States)

    Xiao, Yao; Zhang, Ying-hao; Sheng, Yu-xin; Zhang, Jin-lan

    2008-05-01

    A rapid and specific liquid chromatographic/electrospray ionization mass spectrometric (LC/ESI-MS) method has been developed and validated for the identification and quantification of paeonol in rat plasma. Paeonol and internal standard were isolated from plasma samples by liquid-liquid extraction with chloroform. The chromatographic separation was accomplished on a Zorbax-SB C18 column (100x2.1 mm, 3.5 microm). The mobile phase consisted of acetonitrile and 0.1% aqueous formic acid (64:36) was delivered at a flow rate of 0.2 mL/min. Detection was performed on a single quadrupole mass spectrometer by selected ion monitoring mode via electrospray ionization source. Linearity was established for the range of concentrations 0.0525-15.8 microg/mL with a coefficient correlation (r) of 0.9995. The intra- and inter-day precision (RSD%) was lower than 9.34% and accuracy ranged from 93.7 to 102.3%. The lower limit of quantification was 0.0525 microg/mL. The proposed method was used to determine the concentration of paeonol for pharmacokinetic studies. The pharmacokinetics of different compatibility prescriptions of Su-Xiao-Xin-Tong were studied and compared.

  13. Dynamic contrast-enhanced MR imaging pharmacokinetic parameters as predictors of treatment response of brain metastases in patients with lung cancer.

    Science.gov (United States)

    Kuchcinski, Grégory; Le Rhun, Emilie; Cortot, Alexis B; Drumez, Elodie; Duhal, Romain; Lalisse, Maxime; Dumont, Julien; Lopes, Renaud; Pruvo, Jean-Pierre; Leclerc, Xavier; Delmaire, Christine

    2017-09-01

    To determine the diagnostic accuracy of pharmacokinetic parameters measured by dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in predicting the response of brain metastases to antineoplastic therapy in patients with lung cancer. Forty-four consecutive patients with lung cancer, harbouring 123 newly diagnosed brain metastases prospectively underwent conventional 3-T MRI at baseline (within 1 month before treatment), during the early (7-10 weeks) and midterm (5-7 months) post-treatment period. An additional DCE MRI sequence was performed during baseline and early post-treatment MRI to evaluate baseline pharmacokinetic parameters (K (trans), k ep, v e, v p) and their early variation (∆K (trans), ∆k ep, ∆v e, ∆v p). The objective response was judged by the volume variation of each metastasis from baseline to midterm MRI. ROC curve analysis determined the best DCE MRI parameter to predict the objective response. Baseline DCE MRI parameters were not associated with the objective response. Early ∆K (trans), ∆v e and ∆v p were significantly associated with the objective response (p = 0.02, p = 0.001 and p = 0.02, respectively). The best predictor of objective response was ∆v e with an area under the curve of 0.93 [95% CI = 0.87, 0.99]. DCE MRI and early ∆v e may be a useful tool to predict the objective response of brain metastases in patients with lung cancer. • DCE MRI could predict the response of brain metastases from lung cancer • ∆v e was the best predictor of response • DCE MRI could be used to individualize patients' follow-up.

  14. Quantitative determination of mithramycin in human plasma by a novel, sensitive ultra-HPLC-MS/MS method for clinical pharmacokinetic application.

    Science.gov (United States)

    Roth, Jeffrey; Peer, Cody J; Widemann, Brigitte; Cole, Diane E; Ershler, Rachel; Helman, Lee; Schrump, David; Figg, William D

    2014-11-01

    Mithramycin is a neoplastic antibiotic synthesized by various Streptomyces bacteria. It is under investigation as a chemotherapeutic treatment for a wide variety of cancers. Ongoing and forthcoming clinical trials will require pharmacokinetic analysis of mithramycin in humans, both to see if target concentrations are achieved and to optimize dosing and correlate outcomes (response/toxicity) with pharmacokinetics. Two published methods for mithramycin quantitation exist, but both are immunoassays that lack current bioanalytical standards of selectivity and sensitivity. To provide an upgraded and more widely applicable assay, a UPLC-MS/MS method for quantitation of mithramycin in human plasma was developed. Solid-phase extraction allowed for excellent recoveries (>90%) necessary for high throughput analyses on sensitive instrumentation. However, a ∼55% reduction in analyte signal was observed as a result of plasma matrix effects. Mithramycin and the internal standard chromomycin were separated on a Waters Acquity BEH C18 column (2.1×50 mm, 1.7 μm) and detected using electrospray ionization operated in the negative mode at mass transitions m/z 1083.5→268.9 and 1181.5→269.0, respectively, on an AB Sciex QTrap 5500. The assay range was 0.5-500 ng/mL and proved to be linear (r(2)>0.996), accurate (≤10% deviation), and precise (CV<15%). Mithramycin was stable in plasma at room temperature for 24 h, as well as through three freeze-thaw cycles. This method was subsequently used to quantitate mithramycin plasma concentrations from patients enrolled on two clinical trials at the NCI. Published by Elsevier B.V.

  15. Clinical pharmacokinetics of phenobarbital in neonates

    NARCIS (Netherlands)

    Touw, D J; Graafland, O; Cranendonk, A; Vermeulen, R J; van Weissenbruch, M M

    2000-01-01

    Demographic and clinical pharmacokinetic data collected from term and preterm neonates who were treated with intravenous phenobarbital have been analysed to evaluate the role of patient characteristics in pharmacokinetic parameters. Significant relationships between total body weight (TBW) or body

  16. A Rapid and Selective LC-MS/MS Method for Quantification of Quetiapine in Human Plasma and its Application to Pharmacokinetic Study on Indian Schizophrenia Patients

    Directory of Open Access Journals (Sweden)

    S. Ravinder

    2011-01-01

    Full Text Available A rapid, robust and selective high pressure liquid chromatography–positive electrospray ionization tandem mass spectrometry method has been developed and validated for the quantification of quetiapine (QUE in human plasma with K2EDTA using oxcarbazepine (IS as an internal standard. Analyte and internal standard were extracted from human plasma by solid-phase extraction using acetonitrile. The eluted samples were chromatographed on a C18 column by using a 10:75:15v/v mixture of ammonium formate buffer (5 mM, pH 4.50 and acetonitrile and methanol as an isocratic mobile phase at a flow rate of 0.4 mL/min and analyzed by mass spectrometry in the multiple reaction monitoring mode using the respective [M+H]+ ions, m/z 384.3/253.2 for Quetiapine and m/z 253.1/208.1 for the internal standard. The assay exhibited a linear dynamic range of 5.01 - 2501.04 ng/mL for quetiapine in human plasma. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 2.5 min for each sample made it possible to analyze 300 patient plasma samples per day. The validated method has been successfully used for the estimation of quetiapine in real time schizophrenia patient’s plasma samples for pharmacokinetic study.

  17. Determination of Epimedin B in Rat Plasma and Tissue by LC-MS/MS: Application in Pharmacokinetic and Tissue Distribution Studies

    Directory of Open Access Journals (Sweden)

    Qianru Feng

    2017-01-01

    Full Text Available A simple, sensitive, and specific liquid chromatography tandem mass-spectrometric method was developed and validated for the determination of epimedin B in rat plasma and tissue samples. After being processed with a protein precipitation method, these samples were separated on an Agilent Eclipse XDB-C18 column with an isocratic mobile phase consisting of acetonitrile and 0.1% formic acid aqueous solution (32 : 68, v/v. The calibration curve of epimedin B was linear over the concentration range from 1 to 500 ng/mL in plasma and tissue homogenate. The method was then applied to pharmacokinetic and tissue distribution studies after a single oral administration of Herba Epimedii extract to SD rats. Results showed that epimedin B reached the plasma peak concentration at 0.4 h and the terminal elimination half-life was 1.6 h in rat plasma, and the plasma area under the curve from time zero to infinity (AUC0–∞ was 14.35 μg/L·h. The concentration distribution of epimedin B in rat tissue was in the following order: liver > ovary > womb > lung > kidney > spleen > heart > brain, indicating that the compound could be widely distributed in rat, and the reproductive system may be the principal target of epimedin B for female rat.

  18. Effect of magnetic barrier on the plasma parameters in a Trimix-M galatea

    Science.gov (United States)

    Morozov, A. I.; Bugrova, A. I.; Bishaev, A. M.; Lipatov, A. S.; Kozintseva, M. V.

    2006-11-01

    The parameters of plasma trapped in a Trimix-M galatea with increased values of the magnetic barrier and the energy of a hydrogen plasma bunch injected in the trap have been determined. For a barrier magnetic field of B b ˜ 0.1 T, the plasma confinement time in the trap is τp ≈ 300 μs (which agrees with estimates obtained using formulas describing the classical transfer), the maximum electron density is n e ˜ 5 × 1013 cm-3, and the electron and ion temperatures are T e ≈ 20 eV and T i ˜ 2T e, respectively. The energy of trapped plasma is ˜110 J, and the ratio of the gaskinetic to magnetic pressure in the plasma is β0 ˜ 0.2.

  19. Pharmacokinetics of mitragynine in man

    Directory of Open Access Journals (Sweden)

    Trakulsrichai S

    2015-04-01

    the study without adverse reactions. The median duration of abuse was 1.75 years. We analyzed one subject separately due to the abnormal behavior of blood concentration. From data of nine subjects, the pharmacokinetic parameters established were time to reach the maximum plasma concentration (0.83±0.35 hour, terminal half-life (23.24±16.07 hours, and the apparent volume of distribution (38.04±24.32 L/kg. The urine excretion of unchanged form was 0.14%. The pharmacokinetics were observed to be oral two-compartment model. Conclusion: This was the first pharmacokinetic study in humans, which demonstrated linearity and was consistent with the oral two-compartment model with a terminal half-life of about 1 day. The pharmacokinetic linearity and parameters reported are necessary pharmacological information of Kratom, and there is a possibility for it to be developed medically as a pain killer or better opioid substitute in the future. Keywords: kratom, human, pharmacokinetics

  20. Plasma parameter characterization of a dc multicusp plasma chamber operating in He, Ar and Xe gas

    Energy Technology Data Exchange (ETDEWEB)

    Suanpoot, Pradoong; Vilaithong, Thiraphat; Boonyawan, Dheerawan [Fast Neutron Research Facility, Dept. of Physics, Faculty of Science, Chiang Mai Univ. (Thailand); Rhodes, M.W.

    1998-12-31

    A large dc multicusp plasma chamber has been constructed and installed at Chiang Mai University. The first prototype has a 31.2 cm diameter and a 42.5 cm length and is surrounded by 632 ceramic permanent magnet buttons with a maximum magnetic field of about 2.2 kG for each. The magnetic field at the stainless steel wall with a thickness of 2 mm is about 670 G. A tungsten (W) filament was used as a source of primary electrons. The estimated discharge voltage for helium gas (He), argon gas (Ar), and xenon gas (Xe) was 40 V and the discharge operating current varies from 500 mA to 1 A. Plasmas can be confined within a 20 cm diameter region which are uniformly distributed along the axial path. The plasma density was measured by a single cylindrical Langmuir probe to be between 4.8 x 10{sup 8} - 4.9 x 10{sup 9} cm{sup -3} with 650 watts of power applied to the tungsten filament and the gas pressure inside the chamber of 3.8 x 10{sup -4} Torr. Results of the ion density measurements are described. The proportionality constants in the relation between the ion current density arriving at the plasma electrode and the maximum plasma density and the ion sound speed for helium, argon and xenon are found to be 0.42 {+-} 0.07, 0.59 {+-} 0.08, and 0.46 {+-} 0.06, respectively. (author)

  1. Pharmacokinetic interaction study between ranitidine and metoclopramide.

    Science.gov (United States)

    Leucuţa, Adrian; Vlase, Laurian; Farcău, Dorin; Nanulescu, Mircea

    2004-09-01

    The pharmacokinetics of metoclopramide in healthy volunteers was evaluated to determine if previously repeated doses of ranitidine inhibit the metabolism of the gastrointestinal prokinetic drug. Metoclopramide 20 mg (tablets) in combination with ranitidine 150 mg (tablets) were administered to 14 healthy human volunteers in a two treatment study design, separated by 5 days in which the ranitidine alone was administrated in single p.o. doses twice daily. Plasma concentrations of metoclopramide were determined during a 24 hour period following drug administration. Metoclopramide plasma concentrations were determined by a validated RP-HPLC method. Pharmacokinetic parameters were calculated with compartmental and non-compartmental analysis. In the two periods of treatments, the mean peak plasma concentrations Cmax were 44 ng/ml (metoclopramide alone) and 49.2 ng/ml (metoclopramide and ranitidine). The time taken to reach the peak, Tmax, was 1.15 hrs, and 1.21 hrs, respectively. The total areas under the curve (AUC) was 314.3 ng.hr/ml and 354.06 ng.hr/ml, respectively. The half-life (T 1/2) was 5.6 hr and 6.7 hr. A statistically significant difference was observed for both AUC and half-life of metoclopramide when administered alone or after 5 days of treatment with ranitidine. The experimental data proved the pharmacokinetic interaction between ranitidine of metoclopramide, and suggest monitoring adverse effects in patients.

  2. Impact of plasma parameter on self-organization of electron temperature gradient driven turbulence

    Science.gov (United States)

    Kawai, C.; Idomura, Y.; Maeyama, S.; Ogawa, Y.

    2017-04-01

    Self-organization in the slab electron temperature gradient driven (ETG) turbulence is investigated based on gyrokinetic simulations and the Hasegawa-Mima (HM) equation. The scale and the anisotropy of self-organized turbulent structures vary depending on the Rhines scale and the characteristic scale given by the adiabatic response term in the HM equation. The former is determined by competition between the linear wave dispersion and the nonlinear turbulent cascade, while the latter is given as the scale, at which the turbulent cascade is impeded. These scales are controlled by plasma parameters such as the density and temperature gradient, and the temperature ratio of ion to electron. It is found that depending on the plasma parameters, the ETG turbulence shows either isotropic turbulence or zonal flows, which give significantly different transport levels. Although the modulational instability excites zonal modes regardless of the plasma parameters, the final turbulent structure is determined by the self-organization process.

  3. Variation of plasma parameters of vacuum arc column with gap distance

    Science.gov (United States)

    Han, Wen; Yuan, Zhao; He, Junjia

    2016-07-01

    On the basis of a two-dimensional (2D) magneto-hydrodynamic model, we studied long-gap-distance vacuum arcs in a uniform axial magnetic field and determined the effect of gap distance varying in a large range on plasma parameters. Simulation results showed that with increasing gap distance, the parameters of the plasma near the cathode are almost invariant, except for ion number density, but the parameters of the plasma in front of the anode clearly vary; meanwhile, joule heat gradually becomes the main source of energy for the arc column. In a short gap, a clear current constriction can be found in the entire arc column. Whereas when the gap distance exceeds a certain value, a sharp contraction of the current only arises in front of the anode.

  4. Internal oscillating current-sustained RF plasmas: Parameters, stability, and potential for surface engineering

    DEFF Research Database (Denmark)

    Ostrikov, K.; Tsakadze, E.L.; Tsakadze, Z.L.;

    2005-01-01

    plasma parameters by the optical and Langmuir probes are presented. It is shown that the spatial profiles of the electron density, the effective electron temperature and plasma potential feature a great deal of the radial and axial uniformity compared with conventional sources of inductively coupled......A new source of low-frequency (0.46 MHz) inductively coupled plasmas sustained by the internal planar "unidirectional" RF current driven through a specially designed internal antenna configuration has been developed. The experimental results of the investigation of the optical and global argon...... applications and surface engineering. (c) 2005 Elsevier B.V. All rights reserved....

  5. No effect of short term ranitidine intake on diclofenac pharmacokinetics.

    Science.gov (United States)

    Leucuţa, Adrian; Vlase, Laurian; Farcau, Dorin; Nanulescu, Mircea

    2004-12-01

    The pharmacokinetics of diclofenac sodium in healthy volunteers was evaluated to determine if previously repeated doses of ranitidine inhibited the metabolism of the non-steroidal anti-inflammatory drug. Diclofenac sodium 50 mg (tablets) in combination with ranitidine 150 mg (tablets) were administered to 14 healthy human volunteers in a two treatment study design, separated by 5 days in which the ranitidine alone was administrated in single p.o. doses twice daily. Plasma concentrations of diclofenac were determined during a 12 hour period following drug administration. Diclofenac plasma concentrations were determined by a validated RP-HPLC method. Pharmacokinetic parameters were calculated with compartmental and non-compartmental analysis. In the two periods of treatments, the mean peak plasma concentrations Cmax were 1503.9 ng/ml (diclofenac alone) and 1742.5 ng/ml (diclofenac and ranitidine). The time taken to reach the peak, Tmax, was 0.85 hrs, and 0.82 hrs, respectively. The areas under the curve (AUC0-6) were 1479.9 ng x hr/ml and 1650.3 ng x hr/ml, respectively. Statistically insignificant difference was observed in these pharmaco-kinetic parameters of diclofenac sodium when administered alone or after 5 days of treatment with ranitidine. The experimental data did not suggest any consistent effects of ranitidine upon the pharmacokinetics of diclofenac sodium.

  6. Association of Higher Plasma Vitamin D Binding Protein and Lower Free Calcitriol Levels with Tenofovir Disoproxil Fumarate Use and Plasma and Intracellular Tenofovir Pharmacokinetics: Cause of a Functional Vitamin D Deficiency?

    Science.gov (United States)

    Kiser, Jennifer J.; Stephensen, Charles B.; Hazra, Rohan; Flynn, Patricia M.; Wilson, Craig M.; Rutledge, Brandy; Bethel, James; Pan, Cynthia G.; Woodhouse, Leslie R.; Van Loan, Marta D.; Liu, Nancy; Lujan-Zilbermann, Jorge; Baker, Alyne; Kapogiannis, Bill G.; Gordon, Catherine M.

    2013-01-01

    Tenofovir disoproxil fumarate (TDF) causes bone, endocrine, and renal changes by an unknown mechanism(s). Data are limited on tenofovir pharmacokinetics and these effects. Using baseline data from a multicenter study of HIV-infected youth on stable treatment with regimens containing TDF (n = 118) or lacking TDF (n = 85), we measured cross-sectional associations of TDF use with markers of renal function, vitamin D-calcium-parathyroid hormone balance, phosphate metabolism (tubular reabsorption of phosphate and fibroblast growth factor 23 [FGF23]), and bone turnover. Pharmacokinetic-pharmacodynamic associations with plasma tenofovir and intracellular tenofovir diphosphate concentrations were explored among those receiving TDF. The mean age was 20.9 (standard deviation [SD], 2.0) years; 63% were male; and 52% were African American. Compared to the no-TDF group, the TDF group showed lower mean estimated glomerular filtration rates and tubular reabsorption of phosphate, as well as higher parathyroid hormone and 1,25-dihydroxy vitamin D [1,25-OH(2)D] levels. The highest quintile of plasma tenofovir concentrations was associated with higher vitamin D binding protein, lower free 1,25-OH(2)D, higher 25-OH vitamin D, and higher serum calcium. The highest quintile of intracellular tenofovir diphosphate concentration was associated with lower FGF23. Higher plasma tenofovir concentrations were associated with higher vitamin D binding protein and lower free 1,25-OH(2)D, suggesting a functional vitamin D deficiency explaining TDF-associated increased parathyroid hormone. The finding of lower FGF23 accompanying higher intracellular tenofovir diphosphate suggests that different mechanisms mediate TDF-associated changes in phosphate handling. Separate pharmacokinetic properties may be associated with distinct TDF toxicities: tenofovir with parathyroid hormone and altered calcium balance and tenofovir diphosphate with hypophosphatemia and FGF23 regulation. (The clinical trial

  7. High-performance liquid chromatographic method for the determination of nicardipine in pure, pharmaceutical preparations and plasma and its application to pharmacokinetics in humans

    Directory of Open Access Journals (Sweden)

    Sheikha M. Al-Ghannam

    2009-01-01

    Full Text Available A simple, sensitive and reproducible reversed-phase liquid chromatographic method has been developed and validated for the determination of nicardipine hydrochloride (NC in pure, pharmaceutical preparations, human plasma and the study of the pharmacokinetics of the drug in human body. Nicardipine in plasma were extracted with hexane-butanol (12:1,v/v after addition of borate buffer (0.5 M, pH=9.0, and then measured by HPLC-UV using a Waters Symmetry C18 column as stationary phase and methanol– triethylamine buffer (0.01M pH 4 with acetic acid (70:30 as mobile phase. Nicardipine was quantified by ultraviolet absorbance at 353 nm. The method proved to be linear in the pure drug in the ranges of 15-200 ng/mL (r=0.9989 and 5-40 ?g/mL (r=0.9995, and for the pharmaceutical preparations and plasma for drug concentrations in the range of 5-40 ?g/mL (r =0.9992 and 25-150 ng/mL (r=0.9991, respectively. The lower limit of detection and the lower quantitation limit of NC in plasma were 11.74 and 35.57 ng/mL, respectively. The method is sensitive and reliable for harmacokineticstudies of nicardipine in humans after the oral administration of immediate-release capsules to healthy subjects.

  8. Determination of Sodium Tanshinone IIA Sulfonate in human plasma by LC-MS/MS and its application to a clinical pharmacokinetic study.

    Science.gov (United States)

    Qin, WeiWei; Wang, Bin; Lu, XiaoPei; Liu, HaiMing; Wang, Li; Qi, WeiLin

    2016-03-20

    An assay based on protein precipitation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed and validated for the quantitative analysis of Sodium Tanshinone IIA Sulfonate (STS) in human plasma. After the addition of dehydroepiandrosterone-D5-3-sulfate sodium salt (DHEAS-D5) as internal standard (IS) and formic acid, plasma samples were prepared by one-step protein precipitation with a mixture of acetonitrile and methanol. Isocratic mobile phase consisted of 0.4 mmol/L ammonium formate buffer (16 ppm formic acid)/acetonitrile (40/60, v/v) on a XSELECT™ HSS T3 column. Detection was performed on a triple-quadrupole mass spectrometer utilizing an electrospray ionization (ESI) interface operating in positive ion and selected reaction monitoring (SRM) mode with the precursor to product ion transitions m/z 373.3→357.1 for STS and m/z 373.0→97.8 for the IS. Calibration curves of STS in human plasma were linear (r=0.9957-0.9998) over the concentration range of 2-1000 ng/mL with acceptable accuracy and precision. The lower limit of quantification in human plasma was 2 ng/mL. The validated LC-MS/MS method has been successfully applied to a pharmacokinetic study of STS in Chinese healthy male volunteers.

  9. A sensitive and selective UPLC-MS/MS method for simultaneous determination of 10 alkaloids from Rhizoma Menispermi in rat plasma and its application to a pharmacokinetic study.

    Science.gov (United States)

    Wei, Jinxia; Fang, Linlin; Liang, Xinlei; Su, Dan; Guo, Xingjie

    2015-11-01

    A sensitive and selective liquid chromatography-tandem mass spectrometry method has been developed and validated for simultaneous quantitation of 10 alkaloids (dauricine, daurisoline, N-desmethyldauricine, dauricicoline, dauriporphinoline, bianfugecine, dauricoside, stepholidine, acutumine and acutumidine) from Rhizoma Menispermi in rat plasma. After addition of internal standard (verapamil), plasma samples were pretreated by a single-step protein precipitation with acetonitrile. Chromatographic separation was performed on a Waters BEH C18 column with gradient elution using a mobile phase composed of acetonitrile and water (containing 0.1% formic acid) at a flow rate of 0.3 mL/min. The analytes were detected without interference in the multiple reaction monitoring (MRM) mode with positive electrospray ionization. The validated method exhibited good linearity over a wide concentration range (r≥0.9914), and the lower limits of quantification were 0.01-5.0 ng/mL for all the analytes. The intra-day and inter-day precisions (RSD) at three different levels were both less than 13.4% and the accuracies (RE) ranged from -12.8% to 13.5%. The mean extraction recoveries of analytes and IS from rat plasma were all more than 77%. The validated method was successfully applied to a comparative pharmacokinetic study of 10 alkaloids in rat plasma after oral administration of Rhizoma Menispermi extract.

  10. Development and validation of an RP-HPLC method for the quantitation of odanacatib in rat and human plasma and its application to a pharmacokinetic study.

    Science.gov (United States)

    Police, Anitha; Gurav, Sandip; Dhiman, Vinay; Zainuddin, Mohd; Bhamidipati, Ravi Kanth; Rajagopal, Sriram; Mullangi, Ramesh

    2015-11-01

    A simple, specific, sensitive and reproducible high-performance liquid chromatography (HPLC) assay method has been developed and validated for the estimation of odanacatib in rat and human plasma. The bioanalytical procedure involves extraction of odanacatib and itraconazole (internal standard, IS) from a 200 μL plasma aliquot with simple liquid-liquid extraction process. Chromatographic separation was achieved on a Symmetry Shield RP18 using an isocratic mobile phase at a flow rate of 0.7 mL/min. The UV detection wave length was 268 nm. Odanacatib and IS eluted at 5.5 and 8.6 min, respectively with a total run time of 10 min. Method validation was performed as per US Food and Drug Administration guidelines and the results met the acceptance criteria. The calibration curve was linear over a concentration range of 50.9-2037 ng/mL (r(2) = 0.994). The intra- and inter-day precisions were in the range of 2.06-5.11 and 5.84-13.1%, respectively, in rat plasma and 2.38-7.90 and 6.39-10.2%, respectively, in human plasma. The validated HPLC method was successfully applied to a pharmacokinetic study in rats.

  11. Diagnostics of recombining laser plasma parameters based on He-like ion resonance lines intensity ratios

    Science.gov (United States)

    Ryazantsev, S. N.; Skobelev, I. Yu; Faenov, A. Ya; Pikuz, T. A.; Grum-Grzhimailo, A. N.; Pikuz, S. A.

    2016-11-01

    While the plasma created by powerful laser expands from the target surface it becomes overcooled, i.e. recombining one. Improving of diagnostic methods applicable for such plasma is rather important problem in laboratory astrophysics nowadays because laser produced jets are fully scalable to young stellar objects. Such scaling is possible because of the plasma hydrodynamic equations invariance under some transformations. In this paper it is shown that relative intensities of the resonance transitions in He-like ions can be used to measure the parameters of recombining plasma. Intensity of the spectral lines corresponding to these transitions is sensitive to the density in the range of 1016-1020 cm-3 while the temperature ranges from 10 to 100 eV for ions with nuclear charge Zn ∼ 10. Calculations were carried out for F VIII ion and allowed to determine parameters of plasma jets created by nanosecond laser system ELFIE (Ecole Polytechnique, France) for astrophysical phenomenon modelling. Obtained dependencies are quite universal and can be used for any recombining plasma containing He-like fluorine ions.

  12. [Comparison of the pharmacokinetics and safety of a paclitaxel injection NK and Taxol injection in breast cancer patients].

    Science.gov (United States)

    Sagara, Yoshiaki; Rai, Yoshiaki; Sagara, Yoshiatsu; Matsuyama, Yoshito; Baba, Shinichi; Tamada, Shugo; Sagara, Yasuaki; Ando, Mitsutake

    2009-02-01

    A paclitaxel injection NK (NK) is a generic product containing the same amount of ingredient as a Taxol Injection. We examined the pharmacokinetics and safety of NK compared to the original product in breast cancer patients. As a result, the transition of plasma paclitaxel concentration and pharmacokinetic parameter in NK and the original drug were almost equal, which suggested that these products were bioequivalent. In adjuvant therapy, there was no significant difference in adverse events reported, and these products were approximately equally safe.

  13. Measurements of egg shell plasma parameters using laser-induced breakdown spectroscopy

    Indian Academy of Sciences (India)

    Wenfeng Luo; Xiaoxia Zhao; Shuyuan Lv; Haiyan Zhu

    2015-07-01

    Measurements of 1064 nm laser-induced egg shell plasma parameters are presented in this paper. Of special interests were its elemental identification and the determination of spectroscopic temperature and electron density. The electron temperature of 5956 K was inferred using an improved iterative Boltzmann plot method with six calcium atomic emission lines, and the electron number density of 6.1 × 1016 cm−3 was determined by measuring the width of Stark-broadened once-ionized calcium line at 393.37 nm. Based on the experimental results, the laser-induced egg shell plasma was verified to be optically thin and satisfy local thermodynamic equilibrium (LTE). Furthermore, experiments also demonstrated that the loss of energy due to the reflection of the laser beam from the plasma can be neglected and the inverse bremsstrahlung (IB) absorption was the dominant mechanism of plasma heating at the IR wavelength.

  14. Lindhard's polarization parameter and atomic sum rules in the local plasma approximation

    DEFF Research Database (Denmark)

    Cabrera-Trujillo, R.; Apell, P.; Oddershede, J.

    2017-01-01

    In this work, we analyze the effects of Lindhard polarization parameter, χ, on the sum rule, Sp, within the local plasma approximation (LPA) as well as on the logarithmic sum rule Lp = dSp/dp, in both cases for the system in an initial excited state. We show results for a hydrogenic atom with nuc...

  15. Simultaneous determination of Eleutheroside B and Eleutheroside E in rat plasma by high performance liquid chromatography-electrospray ionization mass spectrometry and its application in a pharmacokinetic study.

    Science.gov (United States)

    Ma, Bo; Zhang, Qi; Liu, Yinhui; Li, Jing; Xu, Qiuyu; Li, Xiaotian; Yang, Xiaojing; Yao, Di; Sun, Jingjing; Cui, Guangbo; Ying, Hanjie

    2013-02-15

    Eleutheroside B and Eleutheroside E, two kinds of the major bioactive saponins of Eleutherococcus senticosus, play a pivotal role in biologic activity. In this study, a specific and sensitive high performance liquid chromatography-electrospray ionization-tandem mass spectrometry method (HPLC-MS/MS) was developed and validated for simultaneous determination of Eleutheroside B and Eleutheroside E in rat plasma. The analytes were extracted from rat plasma via a simple protein precipitation procedure with methanol and polygonin was used as internal standard. Chromatographic separation was achieved on a C18 column using a gradient elution program with acetonitrile and water containing 0.1% ammonium hydroxide solution as the mobile phase, with a flow rate of 0.2mL/min. The detection was performed on a triple-quadrupole tandem mass spectrometer by multiple reactions monitoring (MRM) mode in a negative ion mode via electrospray ionization (ESI). The transition monitored were m/z 371 [M-H](-)→209 for Eleutheroside B, m/z 741[M-H](-)→579 for Eleutheroside E and m/z 389[M-H](-)→277 for internal standard. Linear calibration curves were obtained in the concentration range of 1-2000ng/mL for both (Eleutheroside B and Eleutheroside E), with a lower limit of quantification of 1ng/mL. Extraction recovery was over 80% in plasma. The intra- and inter-day precision (RSD) values were below 12% and accuracy (RE) was -2.80 to 5.70% at three QC levels for both. The assay was successfully applied to study pharmacokinetics behavior in rats after oral and intravenous administration of the single substances (Eleutheroside B and Eleutheroside E). And further research was performed by comparing the difference in pharmacokinetic behavior between the single substances and an aqueous extract of E. senticosus after oral administration. Significant difference in pharmacokinetic characteristics between the single substances and an aqueous extract was found in rat, which would be beneficial for

  16. Measurement Of Plasma Parameters In Micro-Discharge By Wall Probe

    Science.gov (United States)

    Saifutdinov, Almaz; Kudryavtsev, Anatoly; Sysoev, Sergey

    2016-09-01

    The increasing scientific and practical interest for glow discharge at high pressure is largely determined by the fact that their use does not require expensive and huge vacuum equipment. The analysis shows that, in contrast to the well-studied positive column (PC), the basic parameters of the plasma negative glow (NG) and Faraday dark space (FDS) of micro-discharges are studied insufficiently. The difficulties of the experimental diagnostics are associated with the fact that for the fixed values of pL with the increasing gas pressure the length of the micro-discharge decreases. And a small size is extremely difficult to diagnose spatial parameters distribution of micro discharges. Since at a small size introducing traditional Langmuir probe into the plasma capacity is not possible technically, it was proposed to use an additional measuring electrode (wall probe) disposed between the cathode and the anode for measurement of the fast EEDF. With its use we have registered EEDF fast electrons produced in the reaction of Penning ionization out of earlier reach range of high-pressure gas (from 20 to 200 Torr). In this paper by using wall probe we measured the basic parameters of NG plasma in micro-discharge in helium in a wide range of pressures. It is shown that the electrons temperature in the NG plasma is low and amounts to few fraction of 1 eV, which differs from the electron temperature in PC plasma. This allows the use of NG plasma for analysis by gas plasma electron spectroscopy. Authors thanks RNF (Grant 14-19-00311) for the support.

  17. Investigation of Normalization Methods using Plasma Parameters for Laser Induced Breakdown Spectroscopy (LIBS) under simulated Martian Conditions

    OpenAIRE

    Vogt, David; Schröder, Susanne; Hübers, H.-W.

    2017-01-01

    Laser Induced Breakdown Spectroscopy data need to be normalized, especially in the field of planetary exploration We investigated plasma parameters as temperature and electron density for this purpose.

  18. Validated LC-MS/MS method for simultaneous quantification of resveratrol levels in mouse plasma and brain and its application to pharmacokinetic and brain distribution studies.

    Science.gov (United States)

    Ramalingam, Prakash; Ko, Young Tag

    2016-02-01

    A rapid, selective, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine resveratrol levels in plasma and brain tissue in mice for supporting pharmacokinetic and brain distribution studies. Analytes were separated using a Sepax BR-C18 analytical column (5μm, 120Å, 1.0×100mm) and eluted using an isocratic elution mobile phase acetonitrile and 0.01% formic acid [60:40, v/v] at a flow rate of 0.1mL/min. Precursor and product ion transitions for analyte resveratrol m/z 226.9>184.8 and curcumin m/z 367.1>148.9 were monitored using triple quadrupole mass spectrometer with multiple reaction monitoring (MRM) in negative ionization mode. The method was validated with respect to accuracy, within- and between-day precision, linearity, limit of quantification, recovery, and matrix effects of analyte. The inter- and intra-day accuracy and precision were within the range of the US Food and Drug Administration (FDA) acceptance criteria, for both matrices. The method was also successfully applied to pharmacokinetic and brain distribution studies of resveratrol after intravenous administration of free resveratrol and resveratrol-loaded solid lipid nanoparticles to mice. The combined use of serial blood sampling, small sample volume, simple extraction, and capillary depletion method drastically improved resveratrol analysis from biological matrices.

  19. Determination of lansoprazole enantiomers in dog plasma by column-switching liquid chromatography with tandem mass spectrometry and its application to a preclinical pharmacokinetic study.

    Science.gov (United States)

    Wang, Hao; Sun, Yantong; Meng, Xiangjun; Yang, Bo; Wang, Jian; Yang, Yan; Gu, Jingkai

    2015-09-01

    Lansoprazole, a selective proton pump inhibitor, has a chiral benzimidazole sulfoxide structure and is used for the treatment of gastric acid hypersecretory related diseases. To investigate its stereoselective pharmacokinetics, a column-switching liquid chromatography with tandem mass spectrometry method was developed for the determination of lansoprazole enantiomers in dog plasma using (+)-pantoprazole as an internal standard. After a simple protein precipitation procedure with acetonitrile, matrix components left behind after sample preparation were further eliminated from the sample by reversed-phase chromatography on a C18 column. The fluent was fed to a chiral column for the separation of lansoprazole enantiomers. Baseline separation of lansoprazole enantiomers was achieved on a Chiralcel OZ-RH column using acetonitrile/0.1% formic acid in water (35:65, v/v) as the mobile phase at 40°C. The linearity of the calibration curves ranged from 3 to 800 ng/mL for each enantiomer. Intra- and inter-day precisions ranged from 2.1 to 7.3% with an accuracy of ±1.7% for (+)-lansoprazole, and from 1.6 to 6.9% with an accuracy of ±3.5% for (-)-lansoprazole, respectively. The validated method was successfully applied for the stereoselective pharmacokinetic study of lansoprazole in beagle dog after intravenous infusion.

  20. Determination of manassantin B in rat plasma using a high performance liquid chromatography with fluorescence detection and its quantitative application to pharmacokinetic study.

    Science.gov (United States)

    Lee, Jae-Young; Song, Jae-Hyoung; Yoon, In-Soo; Ko, Hyun-Jeong; Kim, Dae-Duk; Cho, Hyun-Jong

    2016-02-01

    A simple, sensitive, rapid, and reproducible analytical method of manassantin B in rat plasma by high performance liquid chromatography with fluorescence detection (HPLC-FL) was developed for its application to pharmacokinetic study in rats. Valsartan (VST) was used as an internal standard (IS) in this quantitative analytical method. Manassantin B and VST were extracted by simple and efficient protein precipitation method. Manassantin B was detected at 282/322nm (excitation/emission) wavelengths using FL detector. The chromatographic separation was obtained with reverse phase C18 column and the mobile phase composed of potassium phosphate buffer containing 0.025% trifluoroacetic acid (pH 2.5; 5mM) and acetonitrile including 0.025% trifluoroacetic acid (20:80, v/v) at 1.0mL/min flow rate. The linearity was established at 25.0-10000ng/mL and the lower limit of detection (LLOD) was 7ng/mL. The intra- and inter-day accuracy and precision values of manassantin B were within±15% of the theroretical values and manassantin B after stability tests were also within the acceptable ranges. Developed assay was also successfully applied to pharmacokinetic study after intravenous administration of manassantin B in rats.

  1. Population pharmacokinetics of olprinone in healthy male volunteers

    Directory of Open Access Journals (Sweden)

    Kunisawa T

    2014-03-01

    Full Text Available Takayuki Kunisawa,1 Hidefumi Kasai,2 Makoto Suda,2 Manabu Yoshimura,3 Ami Sugawara,3 Yuki Izumi,3 Takafumi Iida,3 Atsushi Kurosawa,3 Hiroshi Iwasaki3 1Surgical Operation Department, Asahikawa Medical University Hospital, Hokkaido, Japan; 2Clinical Study Management Division, Bell Medical Solutions Inc, Tokyo, Japan; 3Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Hokkaido, Japan Background: Olprinone decreases the cardiac preload and/or afterload because of its vasodilatory effect and increases myocardial contractility by inhibiting phosphodiesterase III. Purpose: The objective of this study was to characterize the population pharmacokinetics of olprinone after a single continuous infusion in healthy male volunteers. Methods: We used 500 plasma concentration data points collected from nine healthy male volunteers for the study. The population pharmacokinetic analysis was performed using the nonlinear mixed effect model (NONMEM® software. Results: The time course of plasma concentration of olprinone was best described using a two-compartment model. The final pharmacokinetic parameters were total clearance (7.37 mL/minute/kg, distribution volume of the central compartment (134 mL/kg, intercompartmental clearance (7.75 mL/minute/kg, and distribution volume of the peripheral compartment (275 mL/kg. The interindividual variability in the total clearance was 12.4%, and the residual error variability (exponential and additive were 22.2% and 0.129 (standard deviation. The final pharmacokinetic model was assessed using a bootstrap method and visual predictive check. Conclusion: We developed a population pharmacokinetic model of olprinone in healthy male adults. The bootstrap method and visual predictive check showed that this model was appropriate. Our results might be used to develop the population pharmacokinetic model in patients. Keywords: phosphodiesterase III inhibitor, men, pharmacokinetic model

  2. [Influence of fever on cefotaxime pharmacokinetics].

    Science.gov (United States)

    Demotes-Mainard, F; Albin, H; Ragnaud, J M; Gin, H; Vincon, G; Aubertin, J

    1988-02-01

    The role of fever on cefotaxime disposition was studied in ten hyperthermic patients. Each subject received intravenously 1 g of cefotaxime on two separated occasions, first when the body temperature was more than 39 degrees C then during a basal state (37 degrees C). Blood samples were taken over 12 hours and urine was collected for 24 hours after injection. After dosing cefotaxime and its metabolite by high performance liquid chromatography, the pharmacokinetic parameters were calculated, especially: plasma and renal clearance, volume of distribution at steady state, area under the curve, and elimination half-life. There is no significant difference in cefotaxime and desacetylcefotaxime disposition between these two states. Hyperthermia has no influence on pharmacokinetics of this cephalosporin.

  3. The effect of degeneracy parameter on Weibel instability in dense plasma

    Energy Technology Data Exchange (ETDEWEB)

    Mahdavi, M. [Physics Department, Mazandaran University, P.O. Box 47415-416 Babolsar (Iran, Islamic Republic of); Khodadadi Azadboni, F. [Physics Department, Mazandaran University, P.O. Box 47415-416 Babolsar (Iran, Islamic Republic of); Young Researchers Club, Sari Branch, Islamic Azad University, P.O. Box 48161-194 Sari (Iran, Islamic Republic of)

    2013-12-15

    In this paper, the role of degeneracy parameter, in both directions parallel and perpendicular with propagation direction of the laser beam in plasma, on the growth rate of Weibel instability, is studied. Calculations show that with the temperature anisotropy, β = T{sub ∥}/T{sub ⊥} = 0.2 and a 0.75 times reduction of the degeneracy parameter, the increased rate of the the Weibel instability growth rate is 72%. The degeneracy required for minimal growth rate in interaction laser plasma with a density of 1.2 × 10{sup 32}m{sup −3}, is larger than 3. The reduction of temperature and the degeneracy parameter of plasma in parallel direction will also increase growth rate about 30% more than incrossing degeneracy parameter in transverse direction. With the minimum pressure costs of cold compression, subsequent degeneracy parameters, and the minimum value of electron quiver energy, we can expect growth rate of Weibel instability order 0.01.

  4. In vitro enantioselective human liver microsomal metabolism and prediction of in vivo pharmacokinetic parameters of tetrabenazine by DLLME-CE.

    Science.gov (United States)

    Bocato, Mariana Zuccherato; de Lima Moreira, Fernanda; de Albuquerque, Nayara Cristina Perez; de Gaitani, Cristiane Masetto; de Oliveira, Anderson Rodrigo Moraes

    2016-09-05

    A new capillary electrophoresis method for the enantioselective analysis of cis- and trans- dihydrotetrabenazine (diHTBZ) after in vitro metabolism by human liver microsomes (HLMs) was developed. The chiral electrophoretic separations were performed by using tris-phosphate buffer (pH 2.5) containing 1% (w/v) carboxymethyl-β-CD as background electrolyte with an applied voltage of +15kV and capillary temperature kept at 15°C. Dispersive liquid-liquid microextraction was employed to extract the analytes from HLMs. Dichloromethane was used as extraction solvent (75μL) and acetone as disperser solvent (150μL). The method was validated according to official guidelines and showed to be linear over the concentration range of 0.29-19.57μmolL(-1) (r=0.9955) for each metabolite enantiomer. Within- and between-day precision and accuracy evaluated by relative standard deviation and relative error were lower than 15% for all enantiomers. The stability assay showed that the analytes kept stable under handling, storage and in metabolism conditions. After method validation, an enantioselective in vitro metabolism and in vivo pharmacokinetic prediction was carried out. This study showed a stereoselective metabolism and the observed kinetic profile indicated a substrate inhibition behavior. DiHTBZ enantiomers were catalyzed mainly by CYP2C19 and the predicted clearance suggests that liver metabolism is the main route for TBZ elimination which supports the literature data.

  5. A PHARMACOKINETIC STUDY ON RU 486 AND ITS METABOLITES AFTER ORAL ADMINISTRATION AT VARIOUS DOSES

    Institute of Scientific and Technical Information of China (English)

    SHIYong-En; YEZhi-Hou; HEChang-Hai; ZHANGGuo-Qin; XUJian-Qiu; BAJXiu-Mei

    1989-01-01

    The purpose of the present study is to obtain pharmacokinetic parameters of RU486 and its metabolites and then to find out an optimal regimen of the compound for termination of human early pregnancy. Plasma levels of RU486 and its metabolites,

  6. Pharmacokinetics of enterolignans in healthy men and women consuming a single dose of secoisolariciresinol diglucoside

    NARCIS (Netherlands)

    Kuijsten, A.; Arts, I.C.W.; Vree, T.B.; Hollman, P.C.H.

    2005-01-01

    High concentrations of enterolignans in plasma are associated with a lower risk of acute coronary events. However, little is known about the absorption and excretion of enterolignans. The pharmacokinetic parameters and urinary excretion of enterodiol and enterolactone were evaluated after consumptio

  7. Pharmacokinetics of enterolignans in healthy men and women consuming a single dose of secoisolariciresinol diglucoside

    NARCIS (Netherlands)

    Kuijsten, A.; Arts, I.C.W.; Vree, T.B.; Hollman, P.C.H.

    2005-01-01

    High concentrations of enterolignans in plasma are associated with a lower risk of acute coronary events. However, little is known about the absorption and excretion of enterolignans. The pharmacokinetic parameters and urinary excretion of enterodiol and enterolactone were evaluated after consumptio

  8. Effect of ofloxacin and norfloxacin on rifampicin pharmacokinetics in man.

    Science.gov (United States)

    Ezejiofor, Ndidi A; Brown, Sinyeofori; Barikpoar, Ebenezer; Orisakwe, Orish E

    2015-01-01

    The in vivo effects of norfloxacin (NXC) and ofloxacin (OXC) on rifampicin (RIF) pharmacokinetics were investigated in 5 apparently healthy volunteers aged 18-39 years after informed consent. The study was carried out in 3 phases with an interval drug washout period of at least 1 week in between the phases. In phase 1 (RIF alone), the subject received 600 mg of RIF. In phase 2 (RIF + OXC), 600 mg of RIF was coadministered with 200 mg of OXC. In phase 3 (RIF + NXC), each subject received 600 mg of RIF together with 400 mg of NXC after 1 week drug washout period. Drugs were taken orally with 350 mL of water after an overnight fast, and the subjects fasted 3 hours after the administration of drug. Plasma, saliva, and urine concentration of RIF were predetermined at 0 hour and then hourly until the 8th, 12th, 24th, and 48th hour. The urine samples were further collected at 72 hours after drug(s) administration using validated methods. Various pharmacokinetics parameters were calculated. NXC reduced the extent and rate of absorption of RIF. Various pharmacokinetic parameters of RIF significantly differ when administered alone or in combination with OXC and NXC. The mean saliva to plasma ratio of RIF concentration was approximately 0.15. The bioavailability indices of RIF in the saliva and plasma were similar in all the groups. Several pharmacokinetic parameters could be calculated using different body fluid concentrations of RIF. The determination of RIF levels in saliva may be useful in therapeutic drug monitoring and pharmacokinetic studies.

  9. Pharmacokinetics of high-dose intravenous melatonin in humans

    DEFF Research Database (Denmark)

    Andersen, Lars P H; Werner, Mads U; Rosenkilde, Mette Marie

    2016-01-01

    This crossover study investigated the pharmacokinetics and adverse effects of high-dose intravenous melatonin. Volunteers participated in 3 identical study sessions, receiving an intravenous bolus of 10 mg melatonin, 100 mg melatonin, and placebo. Blood samples were collected at baseline and 0, 60......, 120, 180, 240, 300, 360, and 420 minutes after the bolus. Quantitative determination of plasma melatonin concentrations was performed using a radioimmunoassay technique. Pharmacokinetic parameters were estimated by a compartmental pharmacokinetic analysis. Adverse effects included assessments...... of sedation and registration of other symptoms. Sedation, evaluated as simple reaction times, was measured at baseline and 120, 180, 300, and 420 minutes after the bolus. Twelve male volunteers completed the study. Median (IQR) Cmax after the bolus injections of 10 mg and 100 mg of melatonin were 221...

  10. Evolution of plasma parameters in an Ar-N2/He inductive plasma source with magnetic pole enhancement

    Science.gov (United States)

    Maria, Younus; N, U. Rehman; M, Shafiq; M, Naeem; M, Zaka-Ul-Islam; M, Zakaullah

    2017-02-01

    Magnetic pole enhanced inductively coupled plasmas (MaPE-ICPs) are a promising source for plasma-based etching and have a wide range of material processing applications. In the present study Langmuir probe and optical emission spectroscopy were used to monitor the evolution of plasma parameters in a MaPE-ICP Ar-N2/He mixture plasma. Electron density ({n}{{e}}) and temperature ({T}{{e}}), excitation temperature ({T}{{exc}}), plasma potential ({V}{{p}}), skin depth (δ ) and the evolution of the electron energy probability function (EEPF) are reported as a function of radiofrequency (RF) power, pressure and argon concentration in the mixture. It is observed that {n}{{e}} increases while {T}{{e}} decreases with increase in RF power and argon concentration in the mixture. The emission intensity of the argon line at 750.4 nm is also used to monitor the variation of the ‘high-energy tail’ of the EEPF with RF power and gas pressure. The EEPF has a ‘bi-Maxwellian’ distribution at low RF powers and higher pressure in a pure {{{N}}}2 discharge. However, it evolves into a ‘Maxwellian’ distribution at RF powers greater than 70 W for pure {{{N}}}2, and at 50 W for higher argon concentrations in the mixture. The effect of argon concentration on the temperatures of two electron groups in the ‘bi-Maxwellian’ EEPF is examined. The temperature of the low-energy electron group {T}{{L}} shows a decreasing trend with argon addition until the ‘thermalization’ of the two temperatures occurs, while the temperature of high-energy electrons {T}{{H}} decreases continuously.

  11. Simultaneous Determination of Eight Ginsenosides in Rat Plasma by Liquid Chromatography–Electrospray Ionization Tandem Mass Spectrometry: Application to Their Pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Li-Yuan Ma

    2015-12-01

    Full Text Available A high-performance liquid chromatography–electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS method was successfully developed and validated for the identification and determination of eight ginsenosides: ginsenoside Rg1 (1; 20(S-ginsenoside Rh1 (2; 20(S-ginsenoside Rg2 (3; 20(R-ginsenoside Rh1 (4; 20(R-ginsenoside Rg2 (5; ginsenoside Rd (6; 20(S-ginsenoside Rg3 (7; and 20(R-ginsenoside Rg3 (8 in rat plasma. The established rapid method had high linearity, selectivity, sensitivity, accuracy, and precision. The method has been used successfully to study the pharmacokinetics of abovementioned eight ginsenosides for the first time. After an oral administration of total saponins in the stems-leaves of Panax ginseng C. A. Meyer (GTSSL at a dose of 400 mg/kg, the ginsenosides 6, 7, and 8, belonging to protopanaxadiol-type saponins, exhibited relatively long tmax values, suggesting that they were slowly absorbed, while the ginsenosides 1–5, belonging to protopanaxatriol-type saponins, had different tmax values, which should be due to their differences in the substituted groups. Compounds 2 and 4, 3 and 5, 7 and 8 were three pairs of R/S epimerics at C-20, which was interesting that the t1/2 of 20(S-epimers were always longer than those of 20(R-epimers. This pharmacokinetic identification of multiple ginsenosides of GTSSL in rat plasma provides a significant basis for better understanding the clinical application of GTSSL.

  12. Simultaneous determination of dextromethorphan, dextrorphan and doxylamine in human plasma by HPLC coupled to electrospray ionization tandem mass spectrometry: application to a pharmacokinetic study.

    Science.gov (United States)

    Donato, J L; Koizumi, F; Pereira, A S; Mendes, G D; De Nucci, G

    2012-06-15

    In the present study, a fast, sensitive and robust method to quantify dextromethorphan, dextrorphan and doxylamine in human plasma using deuterated internal standards (IS) is described. The analytes and the IS were extracted from plasma by a liquid-liquid extraction (LLE) using diethyl-ether/hexane (80/20, v/v). Extracted samples were analyzed by high performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Chromatographic separation was performed by pumping the mobile phase (acetonitrile/water/formic acid (90/9/1, v/v/v) during 4.0min at a flow-rate of 1.5 mL min⁻¹ into a Phenomenex Gemini® C18, 5 μm analytical column (150 × 4.6 mm i.d.). The calibration curve was linear over the range from 0.2 to 200 ng mL⁻¹ for dextromethorphan and doxylamine and 0.05 to 10 ng mL⁻¹ for dextrorphan. The intra-batch precision and accuracy (%CV) of the method ranged from 2.5 to 9.5%, and 88.9 to 105.1%, respectively. Method inter-batch precision (%CV) and accuracy ranged from 6.7 to 10.3%, and 92.2 to 107.1%, respectively. The run-time was for 4 min. The analytical procedure herein described was used to assess the pharmacokinetics of dextromethorphan, dextrorphan and doxylamine in healthy volunteers after a single oral dose of a formulation containing 30 mg of dextromethorphan hydrobromide and 12.5mg of doxylamine succinate. The method has high sensitivity, specificity and allows high throughput analysis required for a pharmacokinetic study.

  13. LC-MS determination and pharmacokinetic study of six phenolic components in rat plasma after taking traditional Chinese medicinal-preparation: Guanxinning lyophilized powder for injection.

    Science.gov (United States)

    Guo, Xiaorui; Chen, Xiaohui; Li, Li; Shen, Zhenduo; Wang, Xiaoli; Zheng, Ping; Duan, Fangxia; Ma, Yongfen; Bi, Kaishun

    2008-09-15

    A traditional Chinese medicinal preparation (TCMP) named Guanxinning lyophilized powder for injection composed of Salvia miltiorrhiza Bge. (SMB) and Ligusticum chuanxiong Hort. (LCH) was studied. In order to learn the kinetic behaviors of the lyophilized powder and provide proofs for rational administration, we have developed a sensitive and reproducible method for determination and pharmacokinetic study of six main phenolic components {danshensu (DSS), protocatechuic acid (PAC), protocatechuic aldehyde (PAL), chlorogenic acid (CHA), caffeic acid (CAA) and salvianolic acid B (SAB)} of Guanxinning in rat plasma using liquid chromatography-mass spectrometric (LC-MS) method. Sample preparations were carried out by protein precipitation with the addition of methanol followed by liquid-liquid extraction with ethyl acetate-ethyl ether (3:1, v/v) after internal standard (IS, galic acid) spiked. After evaporation to dryness, the resultant residue was reconstituted in methanol and injected onto a Kromasil C(18) column (150 mm x 4.6 mm i.d. with 5 microm particle size). The analytes were analyzed by using negative electrospray ionization (ESI) mass spectrometry in selected ion monitoring (SIM) mode. The method was with good linearity in the range 0.342-85.0 microgmL(-1) for DSS, 0.0647-12.9 microgmL(-1) for PAC, 0.0933-18.7 microgmL(-1) for PAL, 0.0085-3.40 microgmL(-1) for CHA, 0.0138-2.75 microgmL(-1) for CAA and 0.0272-810 microgmL(-1) for SAB (r>0.99). The average extract recoveries of the six analytes from rat plasma were all no less than 75%, the precision and accuracy determined were all within the required limits. This LC-MS method was successfully applied to pharmacokinetic study of the six phenolic components of Guanxinning lyophilized powder for injection in rats.

  14. Determination of ASP3258, a novel phosphodiesterase type 4 inhibitor, in rat plasma by high-performance liquid chromatography with fluorescence detection and its application to pharmacokinetic study.

    Science.gov (United States)

    Ohtsu, Yoshiaki; Takanuki, Fumiyo; Fukunaga, Yasuhisa; Noguchi, Kiyoshi

    2015-02-01

    The potent phosphodiesterase 4 inhibitor ASP3258 contains a carboxylic acid moiety and a naphthyridine ring and is a novel therapeutic agent for asthma and chronic obstructive pulmonary disease. To support the drug development of ASP3258, we developed and validated a simple method for its determination in rat plasma. Following the addition of the analog AS1406604-00 as an internal standard, plasma samples were processed using C18 -bonded solid-phase extraction cartridges under acidic conditions and injected into a high-performance liquid chromatography system with fluorescence detection. Chromatographic separation was achieved on a Shiseido Capcell Pak C18 UG120 column (3.0 × 150 mm, 5 µm) with a mobile phase consisting of acetonitrile-0.5% acetic acid (50:50, v/v). HPLC eluent was monitored with a fluorescence detector set at a wavelength of 315 nm for excitation and 365 nm for emission. The calibration curve was linear over a range of 2.5-250 ng/mL. Validation data demonstrated that the method is selective, sensitive and accurate. In addition, the present method was successfully applied to rat plasma samples from a pharmacokinetic study.

  15. A novel HPLC-MS/MS method for the simultaneous determination of astemizole and its major metabolite in dog or monkey plasma and application to pharmacokinetics.

    Science.gov (United States)

    Back, Hyun-moon; Lee, Jong-Hwa; Chae, Jung-woo; Song, Byungjeong; Seo, Joung-Wook; Yun, Hwi-yeol; Kwon, Kwang-il

    2015-10-10

    Astemizole (AST), a second-generation antihistamine, is metabolized to desmethyl astemizole (DEA), and although it has been removed from the market for inducing QT interval prolongation, it has reemerged as a potential anticancer and antimalarial agent. This report describes a novel high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for simultaneously determining the concentrations of AST and DEA in beagle dog and cynomolgus monkey plasma with simple preparation method and short retention time. Prior to HPLC analyses, the plasma samples were extracted with simple liquid-liquid extraction method. The isocratic mobile phase was 0.025% trifluoroacetic acid (TFA dissolved in acetonitrile) and 20 mM ammonium acetate (94:6) at a flow rate of 0.25 mL/min and diphenhydramine used as internal standard. In MS/MS analyses, precursor ions of the analytes were optimized as protonated molecular ions: [M+H](+). The lower limit of quantification of astemizole was 2.5 ng/mL in both species and desmethyl astemizole were 7.5 ng/mL and 10 ng/mL in dog and monkey plasma, respectively. The accuracy, precision, and stability of the method were in accordance with FDA guidelines for the validation of bioanalytical methods. Finally this validated method was successfully applied to a pharmacokinetic study in dogs and monkeys after oral administration of 10 mg/kg AST.

  16. Simultaneous quantitation of folic acid and 5-methyltetrahydrofolic acid in human plasma by HPLC-MS/MS and its application to a pharmacokinetic study☆

    Institute of Scientific and Technical Information of China (English)

    Xiao-Hong Zheng; Li-Yuan Jiang; Lan-Ting Zhao; Quan-Ying Zhang; Li Ding

    2015-01-01

    A sensitive method based on high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the simultaneous determination of folic acid (FA) and its active metabolite, 5-methyltetrahydrofolic acid (5-M-THF), in human plasma. The analytes were extracted from plasma with methanol solution containing 10 mg/mL of 2-mercaptoethanol and 0.025% (v/v) ammonium hydroxide. FA and 5-M-THF were more stable after the addition of 2-mercaptoethanol and ammonium hydroxide in the sample preparation procedures of this study than they were in the previously published methods. Chromatographic separation was performed on a Hedera ODS-2 column using a gradient elution system of acetonitrile and 1 mM ammonium acetate buffer solution containing 0.6% formic acid as mobile phase. LC-MS/MS was carried out with an ESI ion-source and operated in the multiple reaction monitoring (MRM) mode. The assay was linear over the concentration ranges of 0.249-19.9 ng/mL for FA, and 5.05-50.5 ng/mL for 5-M-THF. The developed LC-MS/MS method offers increased sensitivity for quantification of FA and 5-M-THF in human plasma and was applicable to a pharmacokinetic study of FA and 5-M-THF.

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

    Directory of Open Access Journals (Sweden)

    Rayan G. Alamri

    2017-01-01

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

  18. Development of a Rat Plasma and Brain Extracellular Fluid Pharmacokinetic Model for Bupropion and Hydroxybupropion Based on Microdialysis Sampling, and Application to Predict Human Brain Concentrations.

    Science.gov (United States)

    Cremers, Thomas I F H; Flik, Gunnar; Folgering, Joost H A; Rollema, Hans; Stratford, Robert E

    2016-05-01

    Administration of bupropion [(±)-2-(tert-butylamino)-1-(3-chlorophenyl)propan-1-one] and its preformed active metabolite, hydroxybupropion [(±)-1-(3-chlorophenyl)-2-[(1-hydroxy-2-methyl-2-propanyl)amino]-1-propanone], to rats with measurement of unbound concentrations by quantitative microdialysis sampling of plasma and brain extracellular fluid was used to develop a compartmental pharmacokinetics model to describe the blood-brain barrier transport of both substances. The population model revealed rapid equilibration of both entities across the blood-brain barrier, with resultant steady-state brain extracellular fluid/plasma unbound concentration ratio estimates of 1.9 and 1.7 for bupropion and hydroxybupropion, respectively, which is thus indicative of a net uptake asymmetry. An overshoot of the brain extracellular fluid/plasma unbound concentration ratio at early time points was observed with bupropion; this was modeled as a time-dependent uptake clearance of the drug across the blood-brain barrier. Translation of the model was used to predict bupropion and hydroxybupropion exposure in human brain extracellular fluid after twice-daily administration of 150 mg bupropion. Predicted concentrations indicate that preferential inhibition of the dopamine and norepinephrine transporters by the metabolite, with little to no contribution by bupropion, would be expected at this therapeutic dose. Therefore, these results extend nuclear imaging studies on dopamine transporter occupancy and suggest that inhibition of both transporters contributes significantly to bupropion's therapeutic efficacy.

  19. RP-HPLC Determination and Pharmacokinetic Comparison of Cinnamic Acid in Rat Plasma After Administration of Di-Gu-Pi Decoction and Pure Cinnamic Acid

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A sensitive, simple, and accurate method was developed for the determination and pharmacokinetic comparison of cinnamic acid in rat plasma after the administration of a Traditional Chinese Medicinal preparation, Di-Gu-Pi decoction, and pure cinnamic acid using RP-HPLC. Di-Gu-Pi was extracted with 5% aqueous sodium bicarbonate, which was followed by purification with ion exchange column chromatography. The plasma samples taken from rats were deproteinized with methanol. The reversed-phase(HPLC) system with a Diamonsil C18 column and methanol-acetonitrile-water (8∶32∶60, volume ratio) (adjusted to pH=3.0 with glacial acetic acid) as the mobile phase was employed for the separation of cinnamic acid in the plasma samples. The detection was set at 272 nm and 3-(p-fluorophenyl)-2-propenoic acid was chosen as the internal standard. The calibration curve was linear in a range from 0.10 to 25.0 μg/mL (R2=0.9988, n=9). The precision was 3.42%-10.10%; the between-day precision was 2.84%-8.91%; the accuracy was -1.51%-1.26%; the mean recovery was 99.9%. The method was found to be sensitive, simple, accurate and appropriate for the determination of cinnamic acid.

  20. Cloud point extraction-HPLC method for the determination and pharmacokinetic study of aristolochic acids in rat plasma after oral administration of Aristolochiae Fructus.

    Science.gov (United States)

    Ren, Gang; Huang, Qun; Wu, Jiangang; Yuan, Jinbin; Yang, Gaihong; Yan, Zhihong; Yao, Shouzhuo

    2014-03-15

    Based on cloud-point extraction (CPE), a high performance liquid chromatography method (HPLC) was developed and validated for the determination of aristolochic acids (AAs) in rat plasma after oral administration of Aristolochiae Fructus (AF). Non-ionic surfactant Genapol X-080, an environmentally friendly solvent, was used for the micelle-mediated extraction. Various influencing factors on CPE process were investigated and optimized. AAs were extracted from rat plasma after adding 1ml of 4.5% (v/v) surfactant in the presence of 0.2mol/l HCl and 20mg NaCl, and the incubation temperature and time were 50°C and 10min, respectively. Base-line separation was obtained for the AAs in rat plasma with the optimized chromatography conditions. The detection limits (LOD) reached downward 10ng/ml. The intra-day and inter-day precisions were less than 7.8%, the accuracies were within ±5.5%, and the average recovery factors were in the range of 94.5-105.4%. In comparison with liquid-liquid extraction, the CPE method has a considerable LOD and higher recoveries. The proposed CPE-HPLC method was specific, sensitive and reliable, and could be an effective tool for the determination of AAs in biological matrixes. With the method the pharmacokinetics of AAs were investigated successfully after oral administration of AF by rats.

  1. Simultaneous determination of catechin, epicatechin and epicatechin gallate in rat plasma by LC-ESI-MS/MS for pharmacokinetic studies after oral administration of Cynomorium songaricum extract.

    Science.gov (United States)

    Zhang, Qiu-Hong; Wang, Wen-Biao; Li, Jin; Chang, Yan-Xu; Wang, Yue-Fei; Zhang, Jishu; Zhang, Bo-Li; Gao, Xiu-Mei

    2012-01-01

    A rapid and valid method was developed for simultaneous determination catechin, epicatechin and epicatechin gallate in rat plasmas using scopoletin (103 ng mL(-1)) as an internal standard (IS). The separation was performed on Eclipse plus C18 column (100 mm × 4.6 mm, 1.8 μm) at a flow rate of 0.3 mL min(-1), and acetonitrile-0.1% formic acid was used as mobile phase. The recoveries of three analytes and IS were more than 78.9%. The lower limits of quantitation (LLOQ) in rat plasma were 2.14, 2.38 and 2.08 ng mL(-1) respectively for catechin, epicatechin and epicatechin gallate. Intra-day and inter-day precisions were within 12%. The accuracies were more than 85%. After single oral administration of 15.25 g kg(-1) Cynomorium songaricum extract, C(max) of catechin, epicatechin and epicatechin gallate in rat plasma were respectively 86.69±38.65, 32.57±15.00 and 36.93±12.62 ng mL(-1) while T(max) values were respectively 0.15±0.09, 0.20±0.10 and 0.20±0.13 h. The results demonstrated that the present LC-MS/MS method was sensitive enough for pharmacokinetic study of catichins following oral administration of C. songaricum extract.

  2. Concurrent determination of olanzapine, risperidone and 9-hydroxyrisperidone in human plasma by ultra performance liquid chromatography with diode array detection method: application to pharmacokinetic study.

    Science.gov (United States)

    Siva Selva Kumar, M; Ramanathan, M

    2016-02-01

    A simple and sensitive ultra-performance liquid chromatography (UPLC) method has been developed and validated for simultaneous estimation of olanzapine (OLZ), risperidone (RIS) and 9-hydroxyrisperidone (9-OHRIS) in human plasma in vitro. The sample preparation was performed by simple liquid-liquid extraction technique. The analytes were chromatographed on a Waters Acquity H class UPLC system using isocratic mobile phase conditions at a flow rate of 0.3 mL/min and Acquity UPLC BEH shield RP18 column maintained at 40°C. Quantification was performed on a photodiode array detector set at 277 nm and clozapine was used as internal standard (IS). OLZ, RIS, 9-OHRIS and IS retention times were found to be 0.9, 1.4, .1.8 and 3.1 min, respectively, and the total run time was 4 min. The method was validated for selectivity, specificity, recovery, linearity, accuracy, precision and sample stability. The calibration curve was linear over the concentration range 1-100 ng/mL for OLZ, RIS and 9-OHRIS. Intra- and inter-day precisions for OLZ, RIS and 9-OHRIS were found to be good with the coefficient of variation <6.96%, and the accuracy ranging from 97.55 to 105.41%, in human plasma. The validated UPLC method was successfully applied to the pharmacokinetic study of RIS and 9-OHRIS in human plasma.

  3. Effect of Plasma Nitriding Parameters on the Wear Resistance of Alloy Inconel 718

    Science.gov (United States)

    Kovací, Halim; Ghahramanzadeh ASL, Hojjat; Albayrak, Çigdem; Alsaran, Akgün; Çelik, Ayhan

    2016-11-01

    The effect of the temperature and duration of plasma nitriding on the microstructure and friction and wear parameters of Inconel 718 nickel alloy is investigated. The process of plasma nitriding is conducted in a nitrogen-hydrogen gaseous mixture at a temperature of 400, 500 and 600°C for 1 and 4 h. The modulus of elasticity of the nitrided layer, the micro- and nanohardness, the surface roughness, the friction factor and the wear resistance of the alloy are determined prior to and after the nitriding. The optimum nitriding regime providing the best tribological characteristics is determined.

  4. Effect of process parameters on induction plasma reactive deposition of tungsten carbide from tungsten metal powder

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Tungsten carbide deposit was made directly from tungsten metal powder through the reaction with methane in radio frequency induction plasma. Effect of major process parameters on the induction plasma reactive deposition of tungsten carbide was studied by optical microscopy, scanning electron microscopy, X-ray diffraction analysis, water displacement method, and microhardness test. The results show that methane flow rate, powder feed rate, particle size, reaction chamber pressure and deposition distance have significant influences on the phase composition, density, and microhardness of the deposit. Extra carbon is necessary to ensure the complete conversion of tungsten metal into the carbide.

  5. Effect of pregnancy on topiramate pharmacokinetics in rabbits.

    Science.gov (United States)

    Matar, Kamal M; Marafie, Najlaa A

    2011-05-01

    Pregnancy is associated with various physiological changes that may lead to significant alterations in the pharmacokinetic profiles of many drugs. The present study was designed to investigate the potential effects of pregnancy on the pharmacokinetics of topiramate (TPM) in the rabbit model. Nineteen female New Zealand white rabbits (nine pregnant and 10 non-pregnant) were used in this study. Blood samples were collected from the animals just before receiving TPM orally at a dose of 20 mg/kg and then serially for up to 24 h. TPM plasma samples were analysed using a validated tandem mass spectrometric (LC-MS/MS) method. The mean values of TPM pharmacokinetic parameters (t(1/2), T(max), AUC(0-∞), and CL/F) were significantly modified in pregnant rabbits as compared with non-pregnant group. Pregnancy significantly (P < 0.05) increased TPM half-life (t(1/2)), time to attain the maximum plasma concentration (T(max)), and the area under TPM plasma concentration-time curve (AUC(0-∞)) and decreased the drug's oral clearance (CL/F) compared with non-pregnancy state in rabbits. The present study demonstrates that pregnancy alters the pharmacokinetics of TPM in rabbits in late gestational period and considerable inter-animal variability was observed. The findings of the present study indicate that TPM CL/F is decreased during late pregnancy in the rabbit model.

  6. Influence of demographic factors, basic blood test parameters and opioid type on propofol pharmacokinetics and pharmacodynamics in ASA I-III patients.

    Science.gov (United States)

    Bienert, Agnieszka; Wiczling, Paweł; Zaba, Czesław; Zaba, Zbigniew; Wolc, Anna; Marciniak, Ryszard; Grześkowiak, Edmund; Kusza, Krzysztof

    2011-01-01

    The aim of the study was to examine population pharmacokinetics (PK) and pharmacodynamics (PD) of propofol (CAS 2078-54-8) during total intravenous anesthesia monitored by spectral frequency index (SFx). Twenty-eight patients of ASA physical status I-III (ASA: American Society of Anesthesiologists) scheduled for laparoscopic cholecystectomy were included. In group I an anesthesia was induced with a bolus of propofol (2 mg/kg) and remifentanil (CAS 132875-61-7) (1.0 microg/kg), followed by a continuous infusion of remifentanil. In group II, an alfentanil (CAS 71195-58-9) (10 microg/kg) bolus dose was followed by a continuous infusion of alfentanil. The general anesthetic technique included propofol, opioid and muscle relaxant. During anesthesia, the propofol infusion rate (3-8 mg/kg/h) was adjusted to the SFx value. Venous blood samples were collected from the patients during 240 min after termination of the infusion. A two compartment model was used to describe propofol PK. A standard effect compartment model was used to describe the delay between the effect and the concentration of propofol. The SFx index was linked to the effect site concentrations through a sigmoidal Emax model. The influence of continuous (body weight, age, blood pressure, heart rate and blood oxygenation, serum protein, the erythrocyte count, hemoglobin and hematocrit, serum creatinine and creatinine clearance) and categorical (gender and the type of opioid) covariates on the pharmacokinetic and pharmacodynamic parameters was investigated. PK/PD analysis was performed using NONMEM. All the screened covariates did not influence propofol PK and PD, except of the opioid type. The central compartment volume of propofol was larger in the presence of remifentanil than in the presence of alfentanil.

  7. Pharmacokinetic Study of Praziquantel Enantiomers and Its Main Metabolite R-trans-4-OH-PZQ in Plasma, Blood and Dried Blood Spots in Opisthorchis viverrini-Infected Patients

    Science.gov (United States)

    Meister, Isabel; Kovac, Jana; Duthaler, Urs; Odermatt, Peter; Huwyler, Jörg; Vanobberghen, Fiona; Sayasone, Somphou; Keiser, Jennifer

    2016-01-01

    Background Praziquantel (PZQ) is the treatment of choice for infections with the liver fluke Opisthorchis viverrini, a major health problem in Southeast Asia. However, pharmacokinetic (PK) studies investigating the disposition of PZQ enantiomers (R- and S-PZQ) and its main metabolite, R-trans-4-OH-PZQ, in diseased patients are lacking. The implementation of a dried blood spot (DBS) sampling technique would ease the performance of PK studies in remote areas without clinical facilities. The aim of the present study is to provide data on the disposition of PZQ enantiomers and R-trans-4-OH-PZQ in opisthorchiasis patients and to validate the use of DBS compared to plasma and blood sampling. Methodology/Principal Findings PZQ was administered to nine O. viverrini-infected patients at 3 oral doses of 25 mg/kg in 4 h intervals. Plasma, blood and DBS were simultaneously collected at selected time points from 0 to 24 h post-treatment. PK parameters were determined using non-compartmental analysis. Drug concentrations and areas under the curve (AUC0–24h) measured in the 3 matrices were compared using Bland-Altman analysis. We observed plasma AUC0–24hs of 1.1, 9.0 and 188.7 μg/ml*h and half-lives of 1.1, 3.3 and 6.4 h for R-PZQ, S-PZQ and R-trans-4-OH, respectively. Maximal plasma concentrations (Cmax) of 0.2, 0.9 and 13.9 μg/ml for R-PZQ, S-PQZ and R-trans-4-OH peaked at 7 h for PZQ enantiomers and at 8.7 h for the metabolite. Individual drug concentration measurements and patient AUC0–24hs displayed ratios of blood or DBS versus plasma between 79–94% for R- and S-PZQ, and between 108–122% for R-trans-4-OH. Conclusions/Significance Pharmacodynamic (PD) in vitro studies on PZQ enantiomers and R-trans-4-OH-PZQ are necessary to be able to correlate PK parameters with efficacy. DBS appears to be a valid alternative to conventional venous sampling for PK studies in PZQ-treated patients. PMID:27152952

  8. Pharmacokinetic Study of Praziquantel Enantiomers and Its Main Metabolite R-trans-4-OH-PZQ in Plasma, Blood and Dried Blood Spots in Opisthorchis viverrini-Infected Patients.

    Directory of Open Access Journals (Sweden)

    Isabel Meister

    2016-05-01

    Full Text Available Praziquantel (PZQ is the treatment of choice for infections with the liver fluke Opisthorchis viverrini, a major health problem in Southeast Asia. However, pharmacokinetic (PK studies investigating the disposition of PZQ enantiomers (R- and S-PZQ and its main metabolite, R-trans-4-OH-PZQ, in diseased patients are lacking. The implementation of a dried blood spot (DBS sampling technique would ease the performance of PK studies in remote areas without clinical facilities. The aim of the present study is to provide data on the disposition of PZQ enantiomers and R-trans-4-OH-PZQ in opisthorchiasis patients and to validate the use of DBS compared to plasma and blood sampling.PZQ was administered to nine O. viverrini-infected patients at 3 oral doses of 25 mg/kg in 4 h intervals. Plasma, blood and DBS were simultaneously collected at selected time points from 0 to 24 h post-treatment. PK parameters were determined using non-compartmental analysis. Drug concentrations and areas under the curve (AUC0-24h measured in the 3 matrices were compared using Bland-Altman analysis. We observed plasma AUC0-24hs of 1.1, 9.0 and 188.7 μg/ml*h and half-lives of 1.1, 3.3 and 6.4 h for R-PZQ, S-PZQ and R-trans-4-OH, respectively. Maximal plasma concentrations (Cmax of 0.2, 0.9 and 13.9 μg/ml for R-PZQ, S-PQZ and R-trans-4-OH peaked at 7 h for PZQ enantiomers and at 8.7 h for the metabolite. Individual drug concentration measurements and patient AUC0-24hs displayed ratios of blood or DBS versus plasma between 79-94% for R- and S-PZQ, and between 108-122% for R-trans-4-OH.Pharmacodynamic (PD in vitro studies on PZQ enantiomers and R-trans-4-OH-PZQ are necessary to be able to correlate PK parameters with efficacy. DBS appears to be a valid alternative to conventional venous sampling for PK studies in PZQ-treated patients.

  9. Simultaneous determination of seven alkaloids in rat plasma by UFLC-MS/MS and its application to a pharmacokinetic study after oral administration of Cerebralcare Granule.

    Science.gov (United States)

    Xiaowen, Li; Ling, Tong; Yunfei, Li; Guoxiang, Sun; Dailin, Yang; Herry, Sun

    2016-04-01

    An ultra fast liquid chromatography-tandem mass sepectrometry (UFLC-MS/MS) method was developed for simultaneous determination of seven active alkaloid components (tetrahydropalmatine, corydaline, α-allocryptopine, tetrahydroberberine, tetrahydrocoptisine, tetrahydrocolumbamine and dehydrocorydaline) in rat plasma after oral administration of Cerebralcare Granule. Plasma samples were pretreated by protein precipitation with acetronitrile containing the internal standard diazepam. Chromatographic separation was achieved on a Phenomenex Kinetex C18 column (100×2.1mm, 2.6μm) with gradient elution using mobile phase consisting of acetonitrile -0.1% formic acid in water at a flow rate of 0.3mL/min. The detection was performed on an electrospray ionization triple quadrupole tandem mass spectrometer using multiple reaction monitoring (MRM) with positive ionization mode. The established method was fully validated and proved to be sensitive and specific with lower limits of quantification (LLOQs) all less than 0.0265ng/mL in rat plasma. Good linearities of seven alkaloids were obtained in respective concentration ranges (r>0.9923). The intra- and inter-day precisions were below of 15% for all the seven alkaloids in terms of relative standard deviation (RSD), and the accuracies were ranged from -2.7% to 8.3% in terms of relative error (RE). Extraction recovery, matrix effect and stability were within the required limits in rat plasma. The validated method was successfully applied to investigate the pharmacokinetics of the seven alkaloids in rat plasma after oral administration of Cerebralcare Granule (CG).

  10. A rapid and sensitive HPLC method for the analysis of metronidazole in human plasma: application to single dose pharmacokinetic and bioequivalence studies

    Directory of Open Access Journals (Sweden)

    Jaber Emami

    2006-03-01

    Full Text Available A sensitive, accurate and rapid reverse phase HPLC method was developed to quantitate plasma levels of metronidazole in order to conduct a comparative bioavailability studies. The drug and internal standard were added to plasma samples, vortexed and then zinc sulfate solution was added in order to precipitate the plasma proteins. Samples were centrifuged at 3000 rpm for 10 min. The supernatant layer was separated and analyzed on a phenyl (300 × 4.6mm column, with 5% acetonitrile in 0.1 M KH2PO4 buffer (pH = 4.5 at 324 nm. The standard curve covering 0.15 – 30 μg/ml concentration range, was linear (r2 = 0.9999, relative errors were within 2.48 to 9.15 % and the CV% ranged from 2.999 to 10.796. The method is suitable for bioavailability, pharmacokinetic, and bioequivalent studies in human. The in-vivo study was carried out in 12 healthy volunteers according to a single dose, two-sequence, cross over randomized design. The bioavailability was compared using the total area under the plasma level versus time curve (AUC0-48, AUC0-, peak plasma concentration (Cmax and time to Cmax (Tmax. No statistically significant difference was found between the AUC0- , Cmax and Tmax values of the test and reference, Flagyl® (p > 0.05. The 90% CI for the ratio of the AUC0- (0.94-1.07 and Cmax (0.88-1.03 and the logarithmically transformed AUC0- (0.99-1.01 and Cmax (0.94-1.01 values of the generic product over those of Flagyl® was calculated to be within the acceptable limit of 0.80-1.20 and 0.80-1.25, respectively. It was, therefore, concluded that the generic metronidazole was bioequivalent with the innovator formulation.

  11. Estimation of tulathromycin depletion in plasma and milk after subcutaneous injection in lactating goats using a nonlinear mixed-effects pharmacokinetic modeling approach.

    Science.gov (United States)

    Lin, Zhoumeng; Cuneo, Matthew; Rowe, Joan D; Li, Mengjie; Tell, Lisa A; Allison, Shayna; Carlson, Jan; Riviere, Jim E; Gehring, Ronette

    2016-11-18

    Extra-label use of tulathromycin in lactating goats is common and may cause violative residues in milk. The objective of this study was to develop a nonlinear mixed-effects pharmacokinetic (NLME-PK) model to estimate tulathromycin depletion in plasma and milk of lactating goats. Eight lactating goats received two subcutaneous injections of 2.5 mg/kg tulathromycin 7 days apart; blood and milk samples were analyzed for concentrations of tulathromycin and the common fragment of tulathromycin (i.e., the marker residue CP-60,300), respectively, using liquid chromatography mass spectrometry. Based on these new data and related literature data, a NLME-PK compartmental model with first-order absorption and elimination was used to model plasma concentrations and cumulative excreted amount in milk. Monte Carlo simulations with 100 replicates were performed to predict the time when the upper limit of the 95% confidence interval of milk concentrations was below the tolerance. All animals were healthy throughout the study with normal appetite and milk production levels, and with mild-moderate injection-site reactions that diminished by the end of the study. The measured data showed that milk concentrations of the marker residue of tulathromycin were below the limit of detection (LOD = 1.8 ng/ml) 39 days after the second injection. A 2-compartment model with milk as an excretory compartment best described tulathromycin plasma and CP-60,300 milk pharmacokinetic data. The model-predicted data correlated with the measured data very well. The NLME-PK model estimated that tulathromycin plasma concentrations were below LOD (1.2 ng/ml) 43 days after a single injection, and 62 days after the second injection with a 95% confidence. These estimated times are much longer than the current meat withdrawal time recommendation of 18 days for tulathromycin in non-lactating cattle. The results suggest that twice subcutaneous injections of 2.5 mg/kg tulathromycin are a clinically

  12. Simultaneous quantification of linezolid, tinidazole, norfloxacin, moxifloxacin, levofloxacin, and gatifloxacin in human plasma for therapeutic drug monitoring and pharmacokinetic studies in human volunteers.

    Science.gov (United States)

    Helmy, Sally A

    2013-12-01

    Linezolid may be administered in combination with norfloxacin, gatifloxacin, levofloxacin, moxifloxacin, and tinidazole for the treatment of various infections, such as urinary and respiratory tract infections, to improve the efficacy of the treatment or to reduce the duration of therapy. Knowledge of the antibiotic plasma concentrations combined with bacterial susceptibility evaluated in terms of minimum inhibitory concentration would optimize treatment efficacy while limiting the risk of dose-related adverse effects and avoiding suboptimal concentrations. A new high-performance liquid chromatography assay method was developed and validated for determination of the above-mentioned drugs in small samples of human plasma. After protein precipitation with acetonitrile:methanol (1:1, vol/vol), satisfactory separation was achieved on a Hypersil BDS C18 column (250 × 4.6 mm, 5 μm) using a mobile phase comprising 20 mM sodium dihydrogen phosphate-2 hydrate (pH = 3.2) and acetonitrile at a ratio of 75:25, vol/vol; the elution was isocratic at ambient temperature with a flow rate of 1.5 mL/min. The ultraviolet detector was set at 260 nm. The validated method was applied to assay real plasma samples used for pharmacokinetic studies and therapeutic drug monitoring of the selected drugs. The assay method described was found to be rapid, sensitive, reproducible, precise, and accurate. Linearity was demonstrated over the concentration ranges as follows: 0.1-30 μg/mL for linezolid and tinidazole; 0.05-5 μg/mL for norfloxacin; and 0.1-10 μg/mL for moxifloxacin, levofloxacin, and gatifloxacin (mean r = 0.9999, n = 12). The observed within- and between-day assay precisions were within 12.5%, whereas accuracy ranged between 92.0% and 112% for all the analytes. The lower limit of quantification was 0.1 μg/mL for all the analytes except norfloxacin which was 0.05 μg/mL. This assay method was valid within a wide range of plasma concentrations and may be proposed as a suitable

  13. Pharmacokinetics of rilmenidine in healthy subjects

    Energy Technology Data Exchange (ETDEWEB)

    Genissel, P.; Bromet, N.; Fourtillan, J.B.; Mignot, A.; Albin, H.

    1988-02-24

    Rilmenidine is a novel alpha 2-adrenoceptor agonist, used in the treatment of mild or moderate hypertension at the oral dose of 1 mg once or twice daily. The pharmacokinetic parameters were investigated after single or repeated administration in healthy subjects, using labeled and unlabeled compounds. Rilmenidine was rapidly and extensively absorbed, with an absolute bioavailability factor close to 1 and a maximal plasma concentration achieved within 2 hours. Rilmenidine was not subject to presystemic metabolism. Distribution was independent of the free fraction because rilmenidine was weakly bound to plasma proteins (less than 10%). The volume of distribution was approximately 5 l.kg-1 (315 liters). Elimination was rapid with a total body plasma clearance of approximately 450 ml.min-1 and an elimination half-life of approximately 8 hours. Renal excretion was the major elimination process (two-thirds of the total clearance). Metabolism was very poor, with a renal elimination of rilmenidine as the parent drug (urinary fraction of rilmenidine was about 65% and no metabolite plasma levels were detected). Linear pharmacokinetics were demonstrated for rilmenidine from 0.5 to 2 mg but, at 3 mg, a slight deviation from linearity was observed. In repeated administration, the linear disposition of rilmenidine with dose was confirmed.

  14. Modeling a short cold cathode DC discharge device with controllable plasma parameters

    Science.gov (United States)

    Kudryavtsev, Anatoly; Adams, Steven; Demidov, Vladimir; Bogdanov, Yevgeny

    2009-11-01

    A short (without positive column) DC gas-discharge device with a cold cathode has been modeled. The device consists of the plane disk-shaped cathode and anode while the inter-electrode gap is bounded by a cylindrical wall. The cathode and anode are each 2.5 cm in diameter, and the inter-electrode gap is 12 mm. The wall is made of conducting parts divided by an insulator. The modeling has been performed for argon plasma at 1 Torr pressure. It is demonstrated in the model that spatial distributions of electron density and temperature and argon metastable atom density depend on the DC voltage applied to different conducting parts of the wall. Applied voltage can trap within the device volume energetic electrons arising from atomic and molecular processes in the plasma. This leads to a modification in the heating of slow electrons by energetic electrons and as a result modifies the controlling plasma parameters.

  15. Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide in Healthy Subjects.

    Science.gov (United States)

    Dolder, Patrick C; Schmid, Yasmin; Steuer, Andrea E; Kraemer, Thomas; Rentsch, Katharina M; Hammann, Felix; Liechti, Matthias E

    2017-02-14

    Lysergic acid diethylamide (LSD) is used recreationally and in clinical research. The aim of the present study was to characterize the pharmacokinetics and exposure-response relationship of oral LSD. We analyzed pharmacokinetic data from two published placebo-controlled, double-blind, cross-over studies using oral administration of LSD 100 and 200 µg in 24 and 16 subjects, respectively. The pharmacokinetics of the 100-µg dose is shown for the first time and data for the 200-µg dose were reanalyzed and included. Plasma concentrations of LSD, subjective effects, and vital signs were repeatedly assessed. Pharmacokinetic parameters were determined using compartmental modeling. Concentration-effect relationships were described using pharmacokinetic-pharmacodynamic modeling. Geometric mean (95% confidence interval) maximum plasma concentration values of 1.3 (1.2-1.9) and 3.1 (2.6-4.0) ng/mL were reached 1.4 and 1.5 h after administration of 100 and 200 µg LSD, respectively. The plasma half-life was 2.6 h (2.2-3.4 h). The subjective effects lasted (mean ± standard deviation) 8.2 ± 2.1 and 11.6 ± 1.7 h for the 100- and 200-µg LSD doses, respectively. Subjective peak effects were reached 2.8 and 2.5 h after administration of LSD 100 and 200 µg, respectively. A close relationship was observed between the LSD concentration and subjective response within subjects, with moderate counterclockwise hysteresis. Half-maximal effective concentration values were in the range of 1 ng/mL. No correlations were found between plasma LSD concentrations and the effects of LSD across subjects at or near maximum plasma concentration and within dose groups. The present pharmacokinetic data are important for the evaluation of clinical study findings (e.g., functional magnetic resonance imaging studies) and the interpretation of LSD intoxication. Oral LSD presented dose-proportional pharmacokinetics and first-order elimination up to 12 h. The effects of LSD were related

  16. Parameters Optimization of Plasma Hardening Process Using Genetic Algorithm and Neural Network

    Institute of Scientific and Technical Information of China (English)

    LIU Gu; WANG Liu-ying; CHEN Gui-ming; HUA Shao-chun

    2011-01-01

    Plasma surface hardening process was performed to improve the performance of the AISI 1045 carbon steel.Experiments were carried out to characterize the hardening qualities.A predicting and optimizing model using genetic algorithm-back propagation neural network(GA-BP) was developed based on the experimental results.The non-linear relationship between properties of hardening layers and process parameters was established.The results show that the GA-BP predicting model is reliable since prediction results are in rather good agreement with measured results.The optimal properties of the hardened layer were deduced from GA.And through multi optimizations,the optimum comprehensive performances of the hardened layer were as follows:plasma arc current is 90 A,hardening speed is 2.2 m/min,plasma gas flow rate is 6.0 L/min and hardening distance is 4.3 mm.It concludes that GA-BP mode developed in this study provides a promising method for plasma hardening parameters prediction and optimization.

  17. Pharmacokinetics of antibiotics in pregnancy and labour.

    Science.gov (United States)

    Philipson, A

    1979-01-01

    Few of the articles published on antibiotics and pregnancy are concerned with pharmacokinetics. It is particularly difficult to evaluate possible alterations in pharmacokinetic parameters that may be due to pregnancy. Most data available have been obtained in connection with abortion or delivery. Such data may not be representative for pregnancy as such. Marked changes in most organ systems, particularly in renal function, but in composition and amounts of body fluids as well, make it likely that several pharmacokinetic parameters change, possibly gradually as pregnancy progresses. Accumulated data for several beta-lactam antibiotics, and also for aminoglycosides indicate that antibiotics eliminated mainly by renal excretion will produce lower levels in serum or plasma in pregnant women than in other individuals. Also, the half-life of certain antibiotics in serum is shorter during pregnancy. Transplacental passage occurs for all antibiotics according to the physicochemical properties of the drug. Bolus injections to a pregnant woman are more efficient than continuous infusion in producing high levels of antibiotic in fetal serum and amniotic fluid. Fetal tissue levels are higher following multiple doses than after a single dose. Lower serum levels of antibiotics in pregnant women than in other individuals following the same dosage will be unsatisfactory as micr-organisms are less likely to be affected.

  18. Life Prediction of Atmospheric Plasma-Sprayed Thermal Barrier Coatings Using Temperature-Dependent Model Parameters

    Science.gov (United States)

    Zhang, B.; Chen, Kuiying; Baddour, N.; Patnaik, P. C.

    2017-06-01

    The failure analysis and life prediction of atmospheric plasma-sprayed thermal barrier coatings (APS-TBCs) were carried out for a thermal cyclic process. A residual stress model for the top coat of APS-TBC was proposed and then applied to life prediction. This residual stress model shows an inversion characteristic versus thickness of thermally grown oxide. The capability of the life model was demonstrated using temperature-dependent model parameters. Using existing life data, a comparison of fitting approaches of life model parameters was performed. A larger discrepancy was found for the life predicted using linearized fitting parameters versus temperature compared to those using non-linear fitting parameters. A method for integrating the residual stress was proposed by using the critical time of stress inversion. The role of the residual stresses distributed at each individual coating layer was explored and their interplay on the coating's delamination was analyzed.

  19. Self-bias Dependence on Process Parameters in Asymmetric Cylindrical Coaxial Capacitively Coupled Plasma

    CERN Document Server

    Upadhyay, J; Popović, S; Valente-Feliciano, A -M; Phillips, L; Vušković, L

    2015-01-01

    An rf coaxial capacitively coupled Ar/Cl2 plasma is applied to processing the inner wall of superconducting radio frequency cavities. A dc self-bias potential is established across the inner electrode sheath due to the surface area difference between inner and outer electrodes of the coaxial plasma. The self-bias potential measurement is used as an indication of the plasma sheath voltage asymmetry. The understanding of the asymmetry in sheath voltage distribution in coaxial plasma is important for the modification of the inner surfaces of three dimensional objects. The plasma sheath voltages were tailored to process the outer wall by providing an additional dc current to the inner electrode with the help of an external dc power supply. The dc self-bias potential is measured for different diameter electrodes and its variation on process parameters such as gas pressure, rf power and percentage of chlorine in the Ar/Cl2 gas mixture is studied. The dc current needed to overcome the self-bias potential to make it ...

  20. The possible role of hydrogen sulfide as a modulator of hemostatic parameters of plasma.

    Science.gov (United States)

    Olas, Beata; Kontek, Bogdan

    2014-09-05

    Hydrogen sulfide (H2S) is a well known toxic gas at high levels. However, at physiological levels, H2S may play a role in the pathogenesis of various cardiovascular diseases. The objective was to study the effects of exogenous H2S on the hemostatic parameters (coagulation and fibrinolytic activity) of human plasma. Human plasma was incubated (5, 15 and 30 min) with NaHS as a H2S donor at the final concentration of 0.01-100 μM. Hemostatic factors, such as maximum velocity of clot formation, fibrin lysis half-time, the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) were estimated. Moreover, the aim of our study was to establish the influence of NaHS (10 μM; 5, 15 and 30 min) on the clot formation using the purified fibrinogen. We demonstrated that coagulation/fibrinolytic properties of human plasma incubated with NaHS were changed. APPT, PT and TT of plasma treated with NaHS at tested concentrations--0.01-100 μM were prolonged. We observed that NaHS (0.01-100 μM) reduced fibrin polymerization in whole plasma and 10 μM NaHS also reduced polymerization of purified fibrinogen. In the presence of NaHS (at the low tested concentration--1 μM) the decrease was about 18% (in plasma, p<0.05). Our experiments also showed that NaHS (0.01-100 μM) stimulated the fibrin lysis in whole plasma. However, the time-dependent (5, 15 and 30 min) reduction of fibrin/fibrinogen polymerization and stimulation of fibrin lysis by NaHS (10 μM) was not observed. In conclusion, the present study demonstrates the anticoagulant properties of exogenous H2S in vitro.

  1. Plasma pharmacokinetics, bioavailability and tissue distribution of agnuside following peroral and intravenous administration in mice using liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Ramakrishna, Rachumallu; Bhateria, Manisha; Singh, Rajbir; Puttrevu, Santosh Kumar; Bhatta, Rabi Sankar

    2016-06-01

    Agnuside (AGN), an iridoid glycoside, is the chemotaxonomic marker of the genus Vitex which has gained enormous attention by virtue of its potential health benefits. Regardless of claiming many therapeutic applications reports demonstrating its pharmacokinetics or quantification in biomatrices are lacking. This is the first report which presents a sensitive liquid chromatography coupled to a tandem mass spectrometry (LC-MS/MS) method for the quantification of AGN in mice plasma and various tissues (including liver, intestine, spleen, kidney, heart, lungs and brain). AGN was extracted from the biological samples using protein precipitation followed by liquid-liquid extraction and the separation was achieved on C18 reversed phase column with a mobile phase consisted of 0.1% formic acid in acetonitrile-0.1% formic acid in triple distilled water (92:8, v/v) at a flow rate of 0.7mL/min. The MS/MS detection was performed by electrospray ionization (ESI) using multiple reaction monitoring (MRM) in negative scan mode. The bioanalytical method was found linear over the concentration range of 1-4000ng/mL for plasma and tissue homogenates (r(2)≥0.990). The lower limit of quantitation (LLOQ) for all matrices was 1ng/mL. Intra-day and inter-day variance and accuracy ranged from 90 to 110% and 1-10%, respectively. Matrix effect and recoveries were well within the satisfactory limits. The validated method was applied successfully to measure AGN concentrations in plasma and tissues following intravenous (i.v.) and peroral (p.o.) administration to mice. Maximal AGN concentrations in plasma and tissues were reached within 30-45min. The mean absolute bioavailability (%F) of AGN was∼0.7%. After oral administration, AGN was most abundant in intestine, followed by kidney, liver, spleen, brain, lungs and heart. The identified target tissues of AGN may help in understanding its pharmacological action in vivo.

  2. Simultaneous determination of blonanserin and its metabolite in human plasma and urine by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study.

    Science.gov (United States)

    Wen, Yu-Guan; Ni, Xiao-Jia; Zhang, Ming; Liu, Xia; Shang, De-Wei

    2012-08-15

    Blonanserin is a novel atypical antipsychotic with highly selective receptor antagonist activity to dopamine D₂ and 5-HT(2A). N-desethyl blonanserin (blonanserin C) is its major active metabolite in human plasma. Herein we report a new highly sensitive, selective, and rapid liquid chromatography-tandem mass spectrometry method to determine blonanserin and blonanserin C simultaneously in human plasma and urine, with N-desethyl-chlor-blonanserin (blonanserin D) as internal standard (IS). Blonanserin and blonanserin C were extracted from aliquots of plasma and urine with ethyl acetate and dichloromethane (4:1) as the solvent and chromatographic separation was performed using an Agilent Eclipse Plus C₁₈ column. The mobile phase was composed of: acetonitrile and ammonium formate-formic acid buffer containing 5mM ammonium formate and 0.1% formic acid (87:13, v/v). To quantify blonanserin, blonanserin C, and blonanserin D, respectively, multiple reaction monitoring (MRM) transition of m/z 368.2→297.2, m/z 340.2→297.1, and m/z 356.2→313.3 was performed in positive mode. The analysis time was about 5.5 min. The calibration curve was linear in the concentration range of 0.01-2 ng/ml. The lower limit of quantification reached 0.01 ng/ml. The intra and inter-day precision and relative errors were less than 8.0% and 6.6% for three QC levels in plasma and urine. The current LC-MS/MS method was validated as simple, sensitive, and accurate and has been successfully applied to investigate the pharmacokinetics of blonanserin and blonanserin C in humans. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Simultaneous determination of ivabradine and N-desmethylivabradine in human plasma and urine using a LC-MS/MS method: application to a pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Chengtao Lu

    2012-04-01

    Full Text Available A sensitive and specific liquid-chromatography tandem mass spectrometry (LC-MS/MS assay has been developed and validated for the simultaneous quantification of ivabradine and its active metabolite N-desmethylivabradine in human plasma and urine. The assay employed a single liquid–liquid extraction of the analytes from plasma and urine samples, and diazepam was used as internal standard (IS. The chromatographic separation was achieved on a Diamonsil C18 column (150 mm×4.6 mm, 5 μm, Dikma using a mixture of methanol and aqueous 5 mM ammonium acetate buffer containing 0.2% formic acid (80:20, v/v as mobile phase. The assay for ivabradine and N-desmethylivabradine in plasma showed good linearity (r≥0.99 over the ranges 0.1013–101.3 ng/mL and 0.085–25.5 ng/mL, respectively. The assay for ivabradine and N-desmethylivabradine in urine showed good linearity (r≥0.99 over the ranges 10.13–6078 ng/mL and 8.5–850 ng/mL, respectively. The intra- and inter-day accuracy and precision values were found to be within the assay variability limits (RSD<15% in accordance with FDA guidelines. The methods were successfully used for evaluating the pharmacokinetic properties of ivabradine and N-desmethylivabradine in human plasma and urine in Chinese healthy volunteers.

  4. Versatile particle collection concept for correlation of particle growth and discharge parameters in dusty plasmas

    Science.gov (United States)

    Hinz, A. M.; von Wahl, E.; Faupel, F.; Strunskus, T.; Kersten, H.

    2015-02-01

    The feasibility of collecting nanoparticles from a dusty plasma by means of the neutral drag force is investigated. The nanoparticles are formed in a capacitively coupled asymmetric discharge running in an Ar/C2H2—mixture at a frequency of 13.56 MHz and an RF-power of 9 W. By opening a gate valve between the plasma reactor and a vacuum chamber at a lower pressure at any desired point of the growth cycle of the dust particles a neutral gas flux is induced that drags the particles out of the plasma onto a substrate. By changing the parameters of the collection process, e.g. the substrate positioning or the substrate temperature, the efficiency of the collection process can be adjusted. Information about the particle size distributions is obtained by performing ex situ SEM measurements. As the collection process creates a time stamp in the in situ recorded control parameters, e.g. the self-bias voltage or the process gas pressure, a direct and precise correlation between the control parameters and the particle size distribution is obtained.

  5. Pharmacokinetic interactions of flunixin meglumine and enrofloxacin in ICR mice.

    Science.gov (United States)

    Ogino, Tomoe; Arai, Toshiro

    2007-04-01

    We examined the pharmacokinetic interactions of enrofloxacin and flunixin in male ICR mice that were subcutaneously (SC) administered with both or either one of the drugs. The experiments were performed on the following three groups: flunixin alone (2 mg/kg, SC), combination of flunixin (2 mg/kg, SC) and enrofloxacin (10 mg/kg, SC), and enrofloxacin alone (10 mg/kg, SC). Blood samples were collected at 5, 15 and 30 min, and 1, 2, 3, 4, 5 and 6 h after the drug administration, and the pharmacokinetic parameters of flunixin and enrofloxacin were evaluated from the plasma drug concentrations. Significant changes were detected in the pharmacokinetics of flunixin following its coadministration with enrofloxacin. Coadministration of flunixin and enrofloxacin resulted in a 41% increase of the area under the curve (AUC) and a 53% extension of the terminal half-life of flunixin; moreover, flunixin attained the maximum plasma drug concentration 2.75 times faster than when administered alone. The terminal rate constant and the maximum plasma drug concentration showed significant decreases of 34% and 33%, respectively, following the coadministration of enrofloxacin and flunixin as compared to those following the administration of flunixin alone. In contrast, no significant difference in the pharmacokinetics of enrofloxacin was detected following its coadministration with flunixin, as compared to those following the administration of enrofloxacin alone. Following the administration of enrofloxacin alone or its coadministration with flunixin, the plasma level of ciprofloxacin, the metabolite of enrofloxacin, was very low or undetectable. In conclusion, the pharmacokinetics of flunixin in ICR mice are altered by the coadministration of flunixin and enrofloxacin.

  6. Pharmacokinetics of levodopa.

    Science.gov (United States)

    Contin, Manuela; Martinelli, Paolo

    2010-11-01

    This paper reviews the clinically relevant determinants of levodopa peripheral pharmacokinetics and main observed changes in the levodopa concentration-effect relationship with Parkinson's disease (PD) progression. Available clinically practical strategies to optimise levodopa pharmacokinetics and pharmacodynamics are briefly discussed. Levodopa shows particular pharmacokinetics including an extensive presystemic metabolism, overcome by the combined use of extracerebral inhibitors of the enzyme L: -amino acid decarboxylase and rapid absorption in the proximal small bowel by a saturable facilitated transport system shared with other large neutral amino acids. Drug transport from plasma to the brain is mediated by the same carriers operating in the intestinal mucosa. The main strategies to assure reproducibility of both intestinal absorption and delivery to the brain, and the clinical effect include standardization of levodopa dosing with respect to meal times and a controlled dietary protein intake. Levodopa plasma half-life is very short, resulting in marked plasma drug concentration fluctuations which are matched, as the disease progresses, to swings in the therapeutic response ("wearing-off" phenomena). "Wearing-off" phenomena can also be associated, at the more advanced disease stages, with a "negative", both parkinsonism-exacerbating and dyskinetic effect of levodopa at low, subtherapeutic plasma concentrations. Dyskinesias may also be related to high-levodopa, excessive plasma concentrations. Recognition of the different levodopa toxic response patterns can be difficult on a clinical basis alone and simultaneous monitoring of the levodopa concentration-effect relationship may prove useful to disclose the underlying mechanism and in planning the correct management. Clinically practical strategies to optimise levodopa pharmacokinetics, and possibly its therapeutic response, include liquid drug solutions, controlled release formulations and the use of inhibitors

  7. Development and validation of a high-performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of irinotecan and its main metabolites in human plasma and its application in a clinical pharmacokinetic study.

    Directory of Open Access Journals (Sweden)

    Elena Marangon

    Full Text Available Irinotecan is currently used in several cancer regimens mainly in colorectal cancer (CRC. This drug has a narrow therapeutic range and treatment can lead to side effects, mainly neutropenia and diarrhea, frequently requiring discontinuing or lowering the drug dose. A wide inter-individual variability in irinotecan pharmacokinetic parameters and pharmacodynamics has been reported and associated to patients' genetic background. In particular, a polymorphism in the UGT1A1 gene (UGT1A1*28 has been linked to an impaired detoxification of SN-38 (irinotecan active metabolite to SN-38 glucuronide (SN-38G leading to increased toxicities. Therefore, therapeutic drug monitoring of irinotecan, SN-38 and SN-38G is recommended to personalize therapy. In order to quantify simultaneously irinotecan and its main metabolites in patients' plasma, we developed and validated a new, sensitive and specific HPLC-MS/MS method applicable to all irinotecan dosages used in clinic. This method required a small plasma volume, addition of camptothecin as internal standard and simple protein precipitation. Chromatographic separation was done on a Gemini C18 column (3 μM, 100 mm x 2.0 mm using 0.1% acetic acid/bidistilled water and 0.1% acetic acid/acetonitrile as mobile phases. The mass spectrometer worked with electrospray ionization in positive ion mode and selected reaction monitoring. The standard curves were linear (R2 ≥0.9962 over the concentration ranges (10-10000 ng/mL for irinotecan, 1-500 ng/mL for SN-38 and SN-38G and 1-5000 ng/mL for APC and had good back-calculated accuracy and precision. The intra- and inter-day precision and accuracy, determined on three quality control levels for all the analytes, were always <12.3% and between 89.4% and 113.0%, respectively. Moreover, we evaluated this bioanalytical method by re-analysis of incurred samples as an additional measure of assay reproducibility. This method was successfully applied to a pharmacokinetic study in

  8. A systematic Review on Pharmacokinetic Changes in Critically ill Patients Role of Extracorporeal, Membrane Oxygenation

    Directory of Open Access Journals (Sweden)

    M Mojtahedzadeh

    2011-12-01

    Full Text Available Objective: Several factors including disease condition and different procedures could alter pharmacokinetic profile of drugs in critically ill patients. For optimizing patients outcome, changing in dosing regimen is necessary. Extracorporeal Membrane Oxygenation (ECMO is one of the procedures which could change pharmacokinetic parameters.The aim of this review was to evaluate the effect of ECMO support on pharmacokinetic parameters and subsequently pharmacotherapy. Method: A systematic review was conducted by reviewing all papers found by searching following key words; extracorporeal membrane oxygenation, ECMO, pharmacokinetic and pharmacotherapy in bibliography database. Results: Different drug classes have been studied; mostly antibiotics. Almost all of the studies have been performed in neonates (as a case series. ECMO support is associated with altered pharmacokinetic parameters that may result in acute changes in plasma concentrations with potentially unpredictable pharmacological effect. Altreation in volume of distribution, protein binding, renal or hepatic clearance and sequestration of drugs by ECMO circuit may result in higher or lower doses requirement during ECMO. As yet, definite dosing guideline is not available. ECMO is extensively used recently for therapy and as a procedure affects pharmacokinetics profile along with other factors in critically ill patients. For optimizing the pharmacodynamic response and outcome of patients, drug regimen should be individualized through therapeutic drug monitoring whenever possible.

  9. Simultaneous Determination and Pharmacokinetic Study of Six Components in Rat Plasma by HPLC-MS/MS after Oral Administration of Acanthopanax sessiliflorus Fruit Extract.

    Science.gov (United States)

    Du, Peng; Lei, Mingdao; Liu, Yu; Yang, Shilin

    2016-12-28

    A specific and reliable HPLC-MS/MS method was developed and validated for the simultaneous determination of protocatechuic acid (PCA), scopolin, (-)-pinoresinol-4,4'-di-O-β-d-glucopyranoside (PDG), acanthoside D, acanthoside B and hyperin in rat plasma for the first time. The analytes were separated on a C18 column (50 × 2.1 mm, 1.8 µm) and a triple-quadrupole mass spectrometer equipped with an electrospray ionization (ESI) source was used for detection. The rat plasma sample was prepared using the protein precipitation procedure. The calibration curves were linear over a concentration range of 1.2-1200.0 ng/mL for PCA, 0.96-960.0 ng/mL for scopolin, 1.12-1120.0 ng/mL for PDG, 1.32-1320.0 ng/mL for acanthoside D, 0.99-990.0 ng/mL for acanthoside B and 1.01-1010.0 ng/mL for hyperin. The intra-day and inter-day precision was less than 11.4% and the relative error (RE) was all within ±15%. The validated method was successfully applied to assess the pharmacokinetics characteristics after the extracts of Acanthopanax sessiliflorus fruits were orally administered to the Sprague-Dawley rat.

  10. Simultaneous quantitation of lamivudine, zidovudine and nevirapine in human plasma by liquid chromatography–tandem mass spectrometry and application to a pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Murali Krishna Matta

    2012-10-01

    Full Text Available A rapid and sensitive LC–MS/MS method for the simultaneous quantitation of lamivudine, zidovudine and nevirapine in human plasma using abacavir as internal standard has been developed and validated. The analytes and IS were extracted from plasma by solid phase extraction using Oasis HLB cartridges and separated on a Hypurity Advance C18 column using a mixture of acetonitrile:0.1% formic acid (76:24, v/v at a flow rate of 0.8 mL/min. Detection involved an API-4000 LC–MS/MS with electrospray ionization in the positive ion mode and multiple-reaction monitoring for analysis. The method was validated according to FDA guidelines and shown to provide intra- and inter-day precision and accuracy within acceptable limits in a run time of only 3.5 min. The method was successfully applied to a pharmacokinetic study involving a single oral administration of a combination tablet to human male volunteers.

  11. Simultaneous determination of atorvastatin, amlodipine, ramipril and benazepril in human plasma by LC-MS/MS and its application to a human pharmacokinetic study.

    Science.gov (United States)

    Pilli, Nageswara Rao; Inamadugu, Jaswanth Kumar; Mullangi, Ramesh; Karra, Vijaya Kumari; Vaidya, Jayathirtha Rao; Rao, J V L N Seshagiri

    2011-04-01

    A rapid, simple, sensitive and specific LC-MS/MS method has been developed and validated for the simultaneous estimation of atorvastatin (ATO), amlodipine (AML), ramipril (RAM) and benazepril (BEN) using nevirapine as an internal standard (IS). The API-4000 LC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. Analytes and IS were extracted from plasma by simple liquid-liquid extraction technique using ethyl acetate. The reconstituted samples were chromatographed on C(18) column by pumping 0.1% formic acid-acetonitrile (15:85, v/v) at a flow rate of 1 mL/min. A detailed validation of the method was performed as per the FDA guidelines and the standard curves were found to be linear in the range of 0.26-210 ng/mL for ATO; 0.05-20.5 ng/mL for AML; 0.25-208 ng/mL for RAM and 0.74-607 ng/mL for BEN with mean correlation coefficient of ≥0.99 for each analyte. The intra-day and inter-day precision and accuracy results were well with in the acceptable limits. A run time of 2.5 min for each sample made it possible to analyze more than 400 human plasma samples per day. The developed assay method was successfully applied to a pharmacokinetic study in human male volunteers.

  12. Validated liquid chromatography-tandem mass spectrometry method for quantitative determination of dauricine in human plasma and its application to pharmacokinetic study.

    Science.gov (United States)

    Liu, Xiaoying; Liu, Qian; Wang, Dongmei; Wang, Xueya; Zhang, Peng; Xu, Haiyan; Zhao, Hui; Zhao, Huaiqing

    2010-05-01

    A highly sensitive and selective LC-MS/MS method was developed and validated for the determination of dauricine in human plasma, using protopine as internal standard (IS). The analyte and IS were extracted by liquid-liquid extraction and analyzed by LC-MS/MS. Chromatographic separation was performed on Agilent TC-C(18) column with a mobile phase of methanol-water-glacial acetic acid (60:40:0.8, v/v/v) at a flow rate of 0.7 mL/min. Detection was performed on a triple quadrupole tandem mass spectrum by multiple reaction monitoring (MRM) mode using the electrospray ionization technique in positive mode. The method was linear over the concentration range of 1-200 ng/mL. The lower limit of quantification (LLOQ) was 1 ng/mL in human plasma with acceptable precision and accuracy. The intra- and inter-day precision was less than 5.9% determined from quality control (QC) samples at concentrations of 2.0, 20.0 and 160 ng/mL, and the accuracy was within +/-9.9%. This method was successfully applied for the evaluation of pharmacokinetics of dauricine after oral doses of 100, 300 and 600 mg phenolic alkaloids of menispermum dauricum tablet (PAMDT) to 12 Chinese healthy volunteers.

  13. Simultaneous quantification of methylene blue and its major metabolite, azure B, in plasma by LC-MS/MS and its application for a pharmacokinetic study.

    Science.gov (United States)

    Kim, Soo-Jin; Ha, Dong-Jin; Koo, Tae-Sung

    2014-04-01

    A simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of methylene blue (MB) and its major metabolite, azure B (AZB), in rat plasma. A simple protein precipitation using acetonitrile was followed by injection of the supernatant on to a Zorbax HILIC Plus column (3.5 µm, 2.1 × 100 mm) with isocratic mobile phase consisting of 5 mM ammonium acetate in 10:90 (v/v) water:methanol at a flow rate of 0.3 mL/min and detection in positive ionization mode. The standard curve was linear over the concentration range from 1 to 1000 ng/mL for MB and AZB with coefficient of determination above 0.9930. The lower limit of quantification was 1 ng/mL using 20 μL of rat plasma sample. The intra- and inter-assay precision and accuracy were <12%. The developed analytical method was successfully applied to the pharmacokinetic study of MB and AZB in rats.

  14. A sensitive LC-MS/MS method for simultaneous determination of six flavonoids in rat plasma: application to a pharmacokinetic study of total flavonoids from mulberry leaves.

    Science.gov (United States)

    He, Jun; Feng, Ying; Ouyang, Hui-Zi; Yu, Bin; Chang, Yan-Xu; Pan, Gui-Xiang; Dong, Gai-Ying; Wang, Tao; Gao, Xiu-Mei

    2013-10-01

    A simple and sensitive LC-MS/MS method has been developed and validated for the determination of rutin, isoquercitrin, astragalin, quercetin, kaempferol and isorhamnetin in rat plasma using naringin as the internal standard (IS). The plasma samples were pretreated and extracted by liquid-liquid extraction. Chromatographic separation was accomplished on a C18 column with a 10 min gradient elution using acetonitrile and 0.1% formic acid aqueous solution as mobile phase at a flow rate of 0.3 mL min(-1). A tandem mass spectrometric detection was conducted using multiple reaction monitoring (MRM) via an electrospray ionization (ESI) source and operating in the negative ionization mode. The lower limit of quantitation (LLOQ) of each analyte was lower than 1 ng mL(-1). Intra-day and inter-day precisions were less than 11.9%. The relative errors of accuracy were in the range of -9.2% to 6.1%. The mean recoveries of flavonoids and IS were higher than 53.8%. The proposed method was further applied to investigate the pharmacokinetics of all analytes after a single oral administration of total flavonoids from mulberry leaves to rats.

  15. HPLC determination of five polyphenols in rat plasma after intravenous administration of hawthorn leaves extract and its application to pharmacokinetic study.

    Science.gov (United States)

    Wang, Si-Yuan; Chai, Ji-Yan; Zhang, Wen-Jie; Liu, Xun; DU, Yang; Cheng, Zhong-Zhe; Ying, Xi-Xiang; Kang, Ting-Guo

    2010-11-01

    A simple and specific HPLC-UV method was developed to simultaneously determine five active compounds including vitexin-4"-O-glucoside (VG), vitexin-2"-O-rhamnoside (VR), vitexin (VIT), rutin (RUT) and hyperoside (HP) in rat plasma after intravenous administrating the hawthorn leaves extract (HLE). With baicalin as internal standard (I.S.), sample pretreatment involved a one-step extraction with methanol of 0.2 ml plasma. The HPLC assay was carried out using a Phenomsil C18 analytical column with UV detection at 332 nm. The mobile phase consisted of methanol-acetonitrile-tetrahydrofuran-1% glacial acetic acid (6:1.5:18.5:74, v/v/v/v). The calibration curves were liner over the range of 2.030-500.5, 0.1513-75.64, 0.2507-12.54, 0.5128-25.64 and 0.4032-20.16 µg/ml for VG, VR, VIT, RUT and HP, respectively. The relative standard deviations (RSD) of the intra- and inter-day precisions for the analysis of the five analytes were between 1.0 and 8.9% with accuracies (relative error) below 8.2% for the analysis of the five analytes. The average extraction recoveries of five analytes were more than 82.67 ± 4.74%. The HPLC method herein described was fully validated and successfully applied to the pharmacokinetic studies after intravenous administration of HLE solution to rats over three doses.

  16. Liquid Chromatography/Tandem Mass Spectrometry for the Simultaneous Determination of Alverine and its Metabolite, Monohydroxy Alverine, in Human Plasma: Application to a Pharmacokinetic Study

    Directory of Open Access Journals (Sweden)

    Rahul C. Gavhane

    2011-01-01

    Full Text Available A rapid and sensitive LC-MS-MS method for the determination of alverine (ALV and its major metabolite, monohydroxy alverine (MHA, in human plasma using imipramine as an internal standard was developed and validated. The analytes were extracted from 0.5 mL aliquots of human plasma by solid phase extraction, using oasis cartridge. Chromatographic separation was carried on Thermo Gold C18 column (50 × 4.6 mm, 5 μ at 30 °C, with isocratic mobile phase, a flow rate of 0.4 mL/min and a total run time of 3.5 min. Detection and quantification were performed using a mass spectrometer in the selected reaction-monitoring mode with positive electrospray ionization at m/z 282.3 → 91.11 for alverine, m/z 298.3 → 106.9 for mono-hydroxy-alverine, and m/z 281.0 → 86.0 for internal standard (IS respectively. This assay was linear over a concentration range of 0.060-10 ng/mL with a lower limit of quantification of 0.060 ng/mL for both alverine and monohydroxy alverine. The coefficient of variation for the assay precision were 104.66% and >100.38% for alverine and monohydroxy alverine respectively. This method was successfully applied to a pharmacokinetic study after oral administration of alverine citrate 60 mg capsule in healthy male subjects.

  17. Development and validation of a reliable high-performance liquid chromatographic method for determination of nodakenin in rat plasma and its application to pharmacokinetic study.

    Science.gov (United States)

    Liu, Zhigang; Li, Famei

    2011-10-01

    A simple and reliable high-performance liquid chromatographic (HPLC) method has been developed for the determination of nodakenin in rat plasma. The concentration of nodakenin was determined in plasma samples after deproteinization with methanol using hesperidin as internal standard. HPLC analysis was performed on a Diamonsil C(18) analytical column using acetonitrile-water (25:75, v/v) as the mobile phase and a UV detection at 330 nm. This method was validated in terms of recovery, linearity, accuracy and precision (intra- and inter-day variation). The extraction recoveries were 91.3 ± 10, 87.8 ± 4.8 and 92.6 ± 5.1 at concentrations of 0.500, 5.00 and 40.0 μg/mL, respectively. The standard curve for nodakenin was linear (r(2) ≥ 0.99) over the concentration range 0.250-50.0 μg/mL with a lower limit of quantification of 0.250 μg/mL. The intra- and inter-day precision (relative standard deviation, RSD) values were not higher than 12% and the accuracy (relative error, RE) was within ± 5.8% at three quality control levels. The validated method was successfully applied for the evaluation of the pharmacokinetics of nodakenin in rats after oral administration of Rhizoma et Radix Notopterygii decoction and nodakenin solution.

  18. Simultaneous quantification of two canthinone alkaloids of Picrasma quassioides in rat plasma by liquid chromatography-tandem mass spectrometry and its application to a rat pharmacokinetic study.

    Science.gov (United States)

    Shi, Yuanyuan; Hong, Chunyan; Xu, Jian; Yang, Xiaoling; Xie, Ning; Feng, Feng; Liu, Wenyuan

    2015-04-01

    Picrasma quassioides (D. Don) Benn. is used in traditional Chinese medicine for the treatment of inflammation. Characteristic components of the medicinal extract are canthinone alkaloids. In this study, a sensitive and rapid liquid chromatography with tandem mass spectrometry method has been developed for simultaneous quantification of two major canthinone alkaloids, 5-hydroxy-4-methoxycanthin-6-one and 4,5-dimethoxycanthin-6-one, in rat plasma after oral administration of P. quassioides extract (200 mg/kg). The chromatographic separation was performed on a C18 column using acetonitrile-aqueous 0.1% formic acid (90:10, v/v) as the mobile phase. Plasma samples were prepared for analysis using a simple liquid-liquid extraction with ethyl acetate. Analytes were detected using tandem mass spectrometry in positive multiple reaction monitoring mode. Method validation revealed excellent linearity over the range 1.25-900 ng/mL for 5-hydroxy-4-methoxycanthin-6-one and 0.5-800 ng/mL for 4,5-dimethoxycanthin-6-one with satisfactory intra- and inter-day precision, accuracy and recovery. Samples were stable under the conditions tested. The pharmacokinetic profiles of the analytes in rats showed that both canthinones were rapidly absorbed and that 4,5-dimethoxycanthin-6-one was eliminated faster than 5-hydroxy-4-methoxycanthin-6-one.

  19. Development of an LC-MS/MS method for the quantitation of deoxyglycychloxazol in rat plasma and its application in pharmacokinetic study$

    Institute of Scientific and Technical Information of China (English)

    Rongshan Li; Ruixue Ran; Quansheng Li; Yurong Huang; Yuan Gu; Duanyun Si

    2016-01-01

    Deoxyglycychloxazol (TY501) is a glycyrrhetinic acid derivative which exhibits high anti-inflammatory activity and reduced pseudoaldosteronism compared to glycyrrhetinic acid. In this study, a sensitive and rapid liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was established for the quantitation of TY501 in rat plasma. Plasma samples were treated by precipitating protein with methanol and supernatants were separated by a Symmetry C8 column with the mobile phase consisting of me-thanol and 10 mM ammonium formate (containing 0.1%of formic acid) (90:10, v/v). The selected reaction monitoring (SRM) transitions were performed at m/z 647.4-191.2 for TY501 and m/z 473.3-143.3 for astragaloside aglycone (IS) in the positive ion mode with atmospheric pressure chemical ionization (APCI) source. Calibration curve was linear over the concentration range of 5–5000 ng/mL. The lower limit of quantification was 5 ng/mL. The mean recovery was over 88%. The intra-and inter-day precisions were lower than 6.0% and 12.8%, respectively, and the accuracy was within 71.3%. TY501 was stable under usual storage conditions and handling procedure. The validated method has been successfully applied to a pharmacokinetic study after oral administration of TY501 to rats at a dosage of 10 mg/kg.

  20. Quick and simple LC-MS/MS method for the determination of simvastatin in human plasma: application to pharmacokinetics and bioequivalence studies

    Directory of Open Access Journals (Sweden)

    Suéllen Cristina Rennó Silva

    2014-09-01

    Full Text Available A simple, rapid, and sensitive method based on liquid chromatography-tandem mass spectrometry for the quantitative determination of simvastatin in human plasma was developed and validated. After a simple extraction with methyl tert-butyl ether, the analyte and internal standard (lovastatin were analyzed using reverse-phase liquid chromatography, on a Kinetex C18column (100 × 4.6 mm, 2.6 μm using acetonitrile: ammonium acetate (2 mM + 0.025 % formic acid (70: 30, v/v as a mobile phase in a run time of 3.5 min. Detection was carried out using electrospray positive ionization mass spectrometry in the multiple-reaction monitoring mode. The method was linear over 0.04-40.0 ng/mL concentration range. The mean extraction recovery of simvastatin was 82% (RSD within 15%. Intraday and interday precisions (as relative standard deviation were all ≤8,7% with accuracy (as relative error of ±8%. This rapid and reliable method was successfully applied for a bioequivalence study of 40 mg of simvastatin orally disintegrating tablets in 44 healthy volunteers, showing that this method is suitable for the quantification of simvastatin in human plasma samples for pharmacokinetics and bioequivalence studies.

  1. Validated LC-MS/MS method for quantification of gabapentin in human plasma: application to pharmacokinetic and bioequivalence studies in Korean volunteers.

    Science.gov (United States)

    Park, Jin-Hee; Jhee, Ok-Hwa; Park, Song-Hee; Lee, Jung-Sik; Lee, Min-Ho; Shaw, Leslie M; Kim, Kwang-Hyun; Lee, Jong-Ho; Kim, Yong-Seok; Kang, Ju-Seop

    2007-08-01

    A sensitive validated liquid chromatography-tandem mass spectrometric method (LC-MS/MS) for gabapentin (GB) in human plasma has been developed and applied to pharmacokinetic (PK) and bioequivalence (BE) studies in human. In a randomized crossover design with a 1-week period, each subject received a 300 mg GB capsule. The procedure involves a simple protein precipitation with acetonitrile and separated by LC with a Gemini C(18) column using acetonitrile-10 mm ammonium acetate (20:80, v/v, pH 3.2) as mobile phase. The GB and internal standard [(S)-(+)-alpha-aminocyclohexanepropionic acid hydrate] were analyzed using an LC-API 2000 MS/MS in multiple reaction monitoring mode. The ionization was optimized using ESI(+) and selectivity was achieved using MS/MS analysis, m/z 172.0 --> 154.0 and m/z 172.0 --> 126.0 for GB and IS, respectively. The assay exhibited good linearity over a working range of 20-5000 ng/mL for GB in human plasma with a lower limit of quantitation of 20 ng/mL. No endogenous compounds were found to interfere with the analysis. The accuracy and precision were shown for concentrations over the standard ranges. This method was successfully applied for the PK and BE studies by analysis of blood samples taken up to 36 h after an oral dose of 300 mg of GB in 24 healthy volunteers.

  2. Rapid and sensitive determination of acetylsalicylic acid and salicylic acid in plasma using liquid chromatography-tandem mass spectrometry: application to pharmacokinetic study.

    Science.gov (United States)

    Xu, Xiangrong; Koetzner, Lee; Boulet, Jamie; Maselli, Harry; Beyenhof, Jessica; Grover, Gary

    2009-09-01

    A simple and sensitive analytical method using liquid chromatography-tandem mass spectrometry (LC/MS/MS) for determination of acetylsalicylic acid (aspirin, ASA) and its major metabolite, salicylic acid (SA), in animal plasma has been developed and validated. Both ASA and SA in plasma samples containing potassium fluoride were extracted using acetonitrile (protein precipitation) with 0.1% formic acid in it. 6-Methoxysalicylic acid was used as the internal standard (IS). The compounds were separated on a reversed-phase column. The multiple reaction monitoring mode was used with ion transitions of m/z 178.9 --> 136.8, 137.0 --> 93.0 and 167.0 --> 123.0 for ASA, SA and IS, respectively. The lower limits of quantification for ASA and SA were 3 and 30 ng/mL, respectively. The developed method was successfully applied for the evaluation of pharmacokinetics of ASA and SA after p.o. and i.v. administration of 1 mg/kg to rats.

  3. Development and validation of sensitive LC/MS/MS method for quantitative bioanalysis of levonorgestrel in rat plasma and application to pharmacokinetics study.

    Science.gov (United States)

    Ananthula, Suryatheja; Janagam, Dileep R; Jamalapuram, Seshulatha; Johnson, James R; Mandrell, Timothy D; Lowe, Tao L

    2015-10-15

    Rapid, sensitive, selective and accurate LC/MS/MS method was developed for quantitative determination of levonorgestrel (LNG) in rat plasma and further validated for specificity, linearity, accuracy, precision, sensitivity, matrix effect, recovery efficiency and stability. Liquid-liquid extraction procedure using hexane:ethyl acetate mixture at 80:20 v:v ratio was employed to efficiently extract LNG from rat plasma. Reversed phase Luna column C18(2) (50×2.0mm i.d., 3μM) installed on a AB SCIEX Triple Quad™ 4500 LC/MS/MS system was used to perform chromatographic separation. LNG was identified within 2min with high specificity. Linear calibration curve was drawn within 0.5-50ng·mL(-1) concentration range. The developed method was validated for intra-day and inter-day accuracy and precision whose values fell in the acceptable limits. Matrix effect was found to be minimal. Recovery efficiency at three quality control (QC) concentrations 0.5 (low), 5 (medium) and 50 (high) ng·mL(-1) was found to be >90%. Stability of LNG at various stages of experiment including storage, extraction and analysis was evaluated using QC samples, and the results showed that LNG was stable at all the conditions. This validated method was successfully used to study the pharmacokinetics of LNG in rats after SubQ injection, providing its applicability in relevant preclinical studies. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Simultaneous Determination and Pharmacokinetic Study of Six Components in Rat Plasma by HPLC-MS/MS after Oral Administration of Acanthopanax sessiliflorus Fruit Extract

    Directory of Open Access Journals (Sweden)

    Peng Du

    2016-12-01

    Full Text Available A specific and reliable HPLC-MS/MS method was developed and validated for the simultaneous determination of protocatechuic acid (PCA, scopolin, (−-pinoresinol-4,4′-di-O-β-d-glucopyranoside (PDG, acanthoside D, acanthoside B and hyperin in rat plasma for the first time. The analytes were separated on a C18 column (50 × 2.1 mm, 1.8 µm and a triple-quadrupole mass spectrometer equipped with an electrospray ionization (ESI source was used for detection. The rat plasma sample was prepared using the protein precipitation procedure. The calibration curves were linear over a concentration range of 1.2–1200.0 ng/mL for PCA, 0.96–960.0 ng/mL for scopolin, 1.12–1120.0 ng/mL for PDG, 1.32–1320.0 ng/mL for acanthoside D, 0.99–990.0 ng/mL for acanthoside B and 1.01–1010.0 ng/mL for hyperin. The intra-day and inter-day precision was less than 11.4% and the relative error (RE was all within ±15%. The validated method was successfully applied to assess the pharmacokinetics characteristics after the extracts of Acanthopanax sessiliflorus fruits were orally administered to the Sprague-Dawley rat.

  5. Determination of tulobuterol in rat plasma using a liquid chromatography-tandem mass spectrometry method and its application to a pharmacokinetic study of tulobuterol patch.

    Science.gov (United States)

    Han, Xiao; Liu, Ran; Ji, Lifang; Hui, Mei; Li, Qing; Fang, Liang; Bi, Kaishun

    2016-01-01

    A sensitive and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for determination of tulobuterol in rat plasma for the first time. Plasma samples were extracted by liquid-liquid extraction method with methyl tert-butyl ether and the analyte and clenbuterol (IS) were separated on a Venusil MP C18 column (100mm×2.1mm, 3μm) using 0.1% formic acid-water-methanol as mobile phase, with a runtime of 5min. The analyte was detected in multiple reaction monitoring (MRM) mode with positive electrospray ionization. Transitions of m/z 228.2→154.0 for tulobuterol and m/z 277.1→203.0 for the clenbuterol were monitored. The linear range was 0.5-100ng/ml (r=0.9967) for tulobuterol with the lower limit of quantitation of 0.5ng/ml. The intra-day and inter-day precisions were less than 10.3% for the analyte and the accuracy was less than -8.6%. The RSD of matrix effect and recovery yield were within ±15% of nominal concentrations and tulobuterol was stable during stability studies. The validated method has been successfully applied to a pharmacokinetic study of three doses of tulobuterol patch in rats for the first time.

  6. Modeling Approach and Analysis of the Structural Parameters of an Inductively Coupled Plasma Etcher Based on a Regression Orthogonal Design

    Institute of Scientific and Technical Information of China (English)

    CHENG Jia; ZHU Yu; JI Linhong

    2012-01-01

    The geometry of an inductively coupled plasma (ICP) etcher is usually considered to be an important factor for determining both plasma and process uniformity over a large wafer. During the past few decades, these parameters were determined by the "trial and error" method, resulting in wastes of time and funds. In this paper, a new approach of regression orthogonal design with plasma simulation experiments is proposed to investigate the sensitivity of the structural parameters on the uniformity of plasma characteristics. The tool for simulating plasma is CFD-ACE+, which is commercial multi-physical modeling software that has been proven to be accurate for plasma simulation. The simulated experimental results are analyzed to get a regression equation on three structural parameters. Through this equation, engineers can compute the uniformity of the electron number density rapidly without modeling by CFD-ACE+. An optimization performed at the end produces good results.

  7. Rapid and Sensitive LC-MS/MS Method for the Determination of Metoprolol in Beagle Dog Plasma with a Simple Protein Precipitation Treatment and Its Pharmacokinetic Applications

    Directory of Open Access Journals (Sweden)

    Aihua Hong

    2012-03-01

    Full Text Available : A rapid LC-MS/MS method with good accuracy and sensitivity was developed and validated for the pharmacokinetics study of metoprolol (MP in beagle dogs. The plasma samples were simply precipitated by methanol and then analyzed by LC-MS/MS. An Ultimate XB-C18 column (150 × 2.1 mm ID, 5 μm was used for separation, with methanol-water containing 0.2% formic acid (65:35, v/v as the mobile phase at a flow rate of 0.2 mL/min. Monitoring ions of MP and internal standard (hydroxypioglitazone were m/z 268.1/115.6 and m/z 373.1/150.2, respectively. The linear range was 3.03–416.35 ng/mL with an average correlation coefficient of 0.9996, and the limit of quantification was 3.03 ng/mL. The intra- and inter-day precision was less than 15%. At low, middle and high concentrations, the recovery, the matrix effect and the accuracy was in the range of 76.06%–95.25%, 93.67%–104.19% and 95.20%–99.96% respectively. The method was applied for the pharmacokinetics study of MP tartrate tablets (50 mg. The AUC0-t, Tmax and Cmax were respectively 919.88 ± 195.67 μg/L·h, 0.96 ± 0.33 h, 349.12 ± 78.04 ng/mL.

  8. Pharmacokinetics of BMEDA after Intravenous Administration in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Chih-Hsien Chang

    2014-01-01

    Full Text Available The pharmacokinetics of N,N-bis(2-mercapatoethly-N',N'-diethylenediamine (BMEDA, a molecule that can form a chelate with rhenium-188 (188Re to produce the 188Re-BMEDA-liposomes, was studied. In this work, beagles received a single injection of BMEDA, at doses of 1, 2, or 5 mg/kg; the concentration of BMEDA in the beagles’ plasma was then analyzed and determined by liquid chromatography-mass spectrometry/mass spectrometry. Based on the pharmacokinetic parameters of BMEDA, we found that male and female animals shared similar patterns indicating that the pharmacokinetics of BMEDA is independent of gender differences. In addition, the pharmacokinetics of BMEDA was seen to be non-linear because the increase of mean AUC0–t and AUC0–∞ values tend to be greater than dose proportional while the mean Vss and CL values of BMEDA appeared to be dose dependent. The information on the pharmacokinetics of BMEDA generated from this study will serve as a basis to design appropriate pharmacology and toxicology studies for future human use.

  9. Intrahippocampal Infusion of Crotamine Isolated from Crotalus durissus terrificus Alters Plasma and Brain Biochemical Parameters

    Directory of Open Access Journals (Sweden)

    Rithiele Gonçalves

    2014-11-01

    Full Text Available Crotamine is one of the main constituents of the venom of the South American rattlesnake Crotalus durissus terrificus. Here we sought to investigate the inflammatory and toxicological effects induced by the intrahippocampal administration of crotamine isolated from Crotalus whole venom. Adult rats received an intrahippocampal infusion of crotamine or vehicle and were euthanized 24 h or 21 days after infusion. Plasma and brain tissue were collected for biochemical analysis. Complete blood count, creatinine, urea, glutamic oxaloacetic transaminase (GOT, glutamic pyruvic transaminase (GPT, creatine-kinase (CK, creatine kinase-muscle B (CK-MB and oxidative parameters (assessed by DNA damage and micronucleus frequency in leukocytes, lipid peroxidation and protein carbonyls in plasma and brain were quantified. Unpaired and paired t-tests were used for comparisons between saline and crotamine groups, and within groups (24 h vs. 21 days, respectively. After 24 h crotamine infusion promoted an increase of urea, GOT, GPT, CK, and platelets values (p ≤ 0.01, while red blood cells, hematocrit and leukocytes values decreased (p ≤ 0.01. Additionally, 21 days after infusion crotamine group showed increased creatinine, leukocytes, TBARS (plasma and brain, carbonyl (plasma and brain and micronucleus compared to the saline-group (p ≤ 0.01. Our findings show that crotamine infusion alter hematological parameters and cardiac markers, as well as oxidative parameters, not only in the brain, but also in the blood, indicating a systemic pro-inflammatory and toxicological activity. A further scientific attempt in terms of preserving the beneficial activity over toxicity is required.

  10. Ignitor Plasma Physics Performance in the H-Regime at Various Parameters

    Science.gov (United States)

    Detragiache, P.; Coppi, B.

    2010-11-01

    The plasma physics performance of Ignitor at full (BT = 13 T, Ip = 10 MA) as well as at reduced parameters (BT = 8 T, Ip = 5 MA) in the high confinement mode (H-regime) is assessed using global 0-D modelling. At full parameters, high-Q operation is possible if the heating power (a combination of Ohmic, α and limited ICRF power) is above the threshold value Pthr for H-regime confinement. Different scaling expressions for Pthr yield significantly different results when used with Ignitor parameters. Even with the most pessimistic among the proposed scalingsootnotetextY. R. Martin et al., Journal of Physics: Conference Series, 123, 012033 (2008). the access to H-regime confinement is possible for Ignitor at full field when the ICRH system is operated at the highest frequency and the generated power is less than at lower frequencies. At reduced parameters, the lower Pthr and the augmented ICRF power available (about 10 MW) facilitate access to H-regime confinement, while the plasma performance remains respectable.

  11. Reconstruction of the ion plasma parameters from the current measurements: mathematical tool

    Directory of Open Access Journals (Sweden)

    E. Séran

    Full Text Available Instrument d’Analyse du Plasma (IAP is one of the instruments of the newly prepared ionospheric mission Demeter. This analyser was developed to measure flows of thermal ions at the altitude of ~ 750 km and consists of two parts: (i retarding potential analyser (APR, which is utilised to measure the energy distribution of the ion plasma along the sensor look direction, and (ii velocity direction analyser (ADV, which is used to measure the arrival angle of the ion flow with respect to the analyser axis. The necessity to obtain quick and precise estimates of the ion plasma parameters has prompted us to revise the existing mathematical tool and to investigate different instrumental limitations, such as (i finite angular aperture, (ii grid transparency, (iii potential depression in the space between the grid wires, (iv losses of ions during their passage between the entrance diaphragm and the collector. Simple analytical expressions are found to fit the currents, which are measured by the APR and ADV collectors, and show a very good agreement with the numerical solutions. It was proven that the fitting of the current with the model functions gives a possibility to properly resolve even minor ion concentrations and to find the arrival angles of the ion flow in the multi-species plasma. The discussion is illustrated by an analysis of the instrument response in the ionospheric conditions which are predicted by the International Reference Ionosphere (IRI model.

    Key words. Ionosphere (plasma convection; instruments and techniques – Space plasma physics (experimental and mathematical techniques

  12. Determination of paroxetine in plasma by liquid chromatography coupled to tandem mass spectrometry for pharmacokinetic and bioequivalence studies.

    Science.gov (United States)

    Jhee, Ok Hwa; Seo, Hee Kyoung; Lee, Min Ho; Jeon, Yong Cheol; Shaw, Leslie M; Lee, Seung Hoon; Hur, Yeon; Kim, Kwang-Hyun; Lee, Heon-Soo; Lee, Seo Eun; Kang, Ju Seop

    2007-01-01

    A rapid and validated liquid chromatography coupled to tandem mass spectrometric method (LC-MS-MS) has been developed and applied to pharmacokinetic and bioequivalence studies in 24 healthy male Korean volunteers. The procedure involves a liquid-liquid extraction of paroxetine (CAS 61869-08-7) and fluoxetine (internal standard, CAS 54910-89-3) with ether/methyl chloride (7:3, v/v) and separated by LC equipped with C18 column using acetonitrile: 5 mmol/L ammonium formate (4:3, v/v) as mobile phase. Detection is carried out on an API 2000 MS system by multiple reactions monitoring mode. The ionization was optimized using ESI(+) and selectivity was achieved by MS-MS analysis, mlz 330.0-->192.0 and m/ z 310-->148 for paroxetine and fluoxetine, respectively. The method has a total run time of 1.5 min and was linear over a working range of 0.05-20 ng/mL and the lower limit of quantification was 0.05 ng/ mL. No endogenous compounds were found to interfere with the analysis. The inter-day and intra-day accuracy was in the ranges of 102.69-107.79% and 102.07-109.57%, respectively and precision of inter-day and intra-day expressed as relative standard deviation were 1.86-9.99% and 1.52-6.28%, respectively. The validation of this method on linearity, specificity, accuracy, precision as well as applicability to pharmacokinetic and bioequivalence studies by analysis of blood samples taken up to 72 h after oral administration of 20 mg of paroxetine in 24 healthy volunteers were found to be good performance.

  13. Pharmacokinetic interactions between herbal medicines and prescribed drugs: focus on drug metabolic enzymes and transporters.

    Science.gov (United States)

    Meng, Qiang; Liu, Kexin

    2014-01-01

    Herbal medicines have been widely used for thousands of years, and now are gaining continued popularity worldwide as a complementary or alternative treatment for a variety of diseases, rehabilitation and health care. Since herbal medicines contain more than one pharmacologically active ingredient and are commonly used with many prescribed drugs, there are potential herb-drug interactions. A variety of reported herb-drug interactions are of pharmacokinetic origin, arising from the effects of herbal medicines on metabolic enzymes and/or transporters. Such an alteration in metabolism or transport can result in changes in absorption, distribution, metabolism, and excretion (e.g., induction or inhibition of metabolic enzymes, and modulation of uptake and efflux transporters), leading to changed pharmacokinetics of the concomitantly prescribed drugs. Pharmacokinetic herb-drug interactions have more clinical significance as pharmacokinetic parameters such as the area under the plasma concentration-time curve (AUC), the maximum plasma concentration (Cmax) or the elimination half-life (t1/2) of the concomitant drug alter. This review summarizes the mechanism underlying herb-drug interactions and the approaches to identify the interactions, and discusses pharmacokinetic interactions of eight widely used herbal medicines (Ginkgo biloba, ginseng, garlic, black cohosh, Echinacea, milk thistle, kava, and St. John's wort) with conventional drugs, using various in vitro, animal in vivo, and clinical studies. The increasing understanding of pharmacokinetic herb-drug interactions will make health care professionals and patients pay more attention to the potential interactions.

  14. Pharmacokinetics of fexofenadine

    DEFF Research Database (Denmark)

    Lappin, Graham; Shishikura, Yoko; Jochemsen, Roeline;

    2010-01-01

    ). Fexofenadine was administered to 6 healthy male volunteers in a three way cross-over design. A microdose (100microg) of (14)C-drug was administered orally (period 1) and intravenously by 30min infusion (period 2). In period 3 an intravenous tracer dose (100microg) of (14)C-drug was administered simultaneously......A human pharmacokinetic study was performed to assess the ability of a microdose to predict the pharmacokinetics of a therapeutic dose of fexofenadine and to determine its absolute oral bioavailability. Fexofenadine was chosen to represent an unmetabolized transporter substrate (P-gP and OATP...... with an oral unlabelled therapeutic dose (120mg). Plasma was collected from all 3 periods and analysed for both total (14)C content and parent drug by accelerator mass spectrometry (AMS). For period 3, plasma samples were also analysed using HPLC-fluorescence to determine total drug concentration. Urine...

  15. Stereoselective analysis of nebivolol isomers in human plasma by high-performance liquid chromatography-tandem mass spectrometry: application in pharmacokinetics.

    Science.gov (United States)

    Neves, Daniel Valente; Vieira, Carolina Pinto; Coelho, Eduardo Barbosa; Marques, Maria Paula; Lanchote, Vera Lucia

    2013-12-01

    Nebivolol is available for clinical use as a racemic mixture. Isomer d-nebivolol (SRRR) is a β1 adrenergic receptor blocker and its antipode, l-nebivolol (RSSS) is responsible for endothelium-dependent NO liberation. This report describes the development and validation of a method of analysis of nebivolol isomers in human plasma by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Nebivolol isomers were extracted from 2mL aliquots of plasma spiked with tramadol as internal standard, alkalinized and added of sodium chloride and diisopropyl ether:dichloromethane (70:30, v/v). Nebivolol isomers were resolved on a Chirobiotic(®) V column using methanol:acetic acid:diethylamine (100:0.15:0.05, v/v/v) as mobile phase. Protonated ion and respective ion product were monitored in transitions 406>151 for nebivolol and 264>58 for internal standard tramadol. There was no racemization of nebivolol isomers during the procedures of sample preparation and chromatographic analysis and matrix effect was absent. Analysis of nebivolol isomers showed linearity for plasma concentrations of 25-2500pg/mL of each isomer. The quantification limit was 25pg of each isomer/mL of plasma. Variation coefficients and inaccuracy calculated in precision and accuracy determinations were lower than 15%. Nebivolol was stable in human plasma after three successive cycles of freezing and thawing, during 4h at room temperature and after processing during 12h in the auto sampler at 5°C showing deviation values lower than 15%. The method was applied in a study of the kinetic disposition of nebivolol in plasma samples collected until 48h after administration of an oral single dose of 10mg of racemic nebivolol hydrochloride to a patient with systemic arterial hypertension. The clinical study demonstrated that the nebivolol pharmacokinetics is stereoselective. Isomer l-nebivolol showed higher AUC(0-∞) (9.4ng/h/mL vs. 4.7ng/h/mL) and smaller apparent clearance (Cl/f) (531.8L/h vs

  16. Rocket measurements within a polar cap arc - Plasma, particle, and electric circuit parameters

    Science.gov (United States)

    Weber, E. J.; Ballenthin, J. O.; Basu, S.; Carlson, H. C.; Hardy, D. A.; Maynard, N. C.; Kelley, M. C.; Fleischman, J. R.; Pfaff, R. F.

    1989-01-01

    Results are presented from the Polar Ionospheric Irregularities Experiment (PIIE), conducted from Sondrestrom, Greenland, on March 15, 1985, designed for an investigation of processes which lead to the generation of small-scale (less than 1 km) ionospheric irregularities within polar-cap F-layer auroras. An instrumented rocket was launched into a polar cap F layer aurora to measure energetic electron flux, plasma, and electric circuit parameters of a sun-aligned arc, coordinated with simultaneous measurements from the Sondrestrom incoherent scatter radar and the AFGL Airborne Ionospheric Observatory. Results indicated the existence of two different generation mechanisms on the dawnside and duskside of the arc. On the duskside, parameters are suggestive of an interchange process, while on the dawnside, fluctuation parameters are consistent with a velocity shear instability.

  17. Comparative pharmacokinetics of chlorogenic acid after oral administration in rats

    Institute of Scientific and Technical Information of China (English)

    Wei Qi; Ting Zhao; Wen-Wen Yang; Guang-Hou Wang; Hua Yua; Hai-Xiao Zhao; Chen Yang; Li-Xin Suna

    2011-01-01

    The present study was aimed at the comparison of the pharmacokinetics of pure chlorogenic acid and extract of Solanum lyratum Thunb. The animals were allocated to two groups, and were administered chlorogenic acid or extract of S. lyratum Thunb. at a dose of 50.0 mg/kg orally. Blood samples were collected up to 8 h post-dosing. Plasma chlorogenic acid analyses were performed using an HPLC method with UV detector. The pharmacokinetic parameters were evaluated using non-compartmental assessment. Significant differences existed in the two groups for AUCo-t, AUCo-∞ and CLz/F. The reliable HPLC method was successfully applied to the determination of chlorogenic acid in rat plasma at dosting of 50.0 mg/kz.

  18. Effect of process parameters on coating composition of cathodic-plasma-electrolysis-treated copper

    Indian Academy of Sciences (India)

    ASIYEH HABIBI; S MOHAMMAD MOUSAVI KHOIE; FARZAD MAHBOUBI; MUSTAFA URGEN

    2017-04-01

    Cathodic plasma electrolysis is a novel technique to form nanostructured layers on metallic surfaces by application of high voltage in a suitable aqueous electrolyte. In the present study, copper is treated by plasma electrolysisin 50 vol% ethanol electrolyte and coatings comprising carbon nanostructure and copper oxide are formed on the copper. The effect of some process parameters such as electrical conductivity, volume and temperature of electrolyte and ratio of anode to cathode surface area on current–voltage behaviour and subsequently coating compositions are investigated at 150V deposition voltage. The composition and morphology of these coatings are characterized by X-ray diffraction, Raman spectroscopy and scanning electron microscopy. Different current–voltage behaviours, temperatures of substrate and the contents and energies of radicals and ions around the substrate by changes in the mentioned parameters cause different compositions from 100 vol% copper oxide to different ratios of copper oxide to carbon, the structure changing from amorphous to graphitic structure in carbon and amorphous to cubic morphology in copper oxide on the substrate. Therefore, the understanding of cathodic plasma electrolysiscan be developed.

  19. DYNAMIC OF CHANGES OF BLOOD PLASMA ENERGY METABOLISM PARAMETERS IN SUCKLING COWS DURING CALVING INTERVAL

    Directory of Open Access Journals (Sweden)

    Ales Pavlik

    2015-02-01

    Full Text Available In this study, effect of environmental condition changes during gazing period on energy metabolism parameters was investigated. Totally 40 Aberdeen Angus cows were selected for observation. Calving all of cows was situated into March. The feeding ration for the animals was comprised by pasture during the grazing period and corn silage, hay and granulated distiller’s grains during the winter period. At average age 9 days before calving, and subsequently 10, 81, 151, 189 and 273 days after calving, blood was sampled and analysed for glucose and NEFA (non-esterified fatty acid concentrations on KONELAB T20xt automatic analyser (Thermo Fisher Scientific, Finland and currently available commercial kits (Biovendor-Laboratorni medicina, Czech Republic. A rapid increase (p < 0.05 of glucose concentration was detected in blood plasma of cows in period before calving to 81 days post partum. Average value of glucose concentration at 273 days postpartum was significant (p < 0.05 lower comparing to day 189. The highest concentrations of NEFA in blood plasma of cows were found at 10 day postpartum. After that, during the persisted higher temperature period the NEFA concentration decreased significantly (p < 0.01 till 189 days postpartum. At the end of monitored period concentration of NEFA in blood plasma significantly decreased (p < 0.05. Changes of hot and cold season during the grazing period probably according to forage quality and had significant effects on blood plasma NEFA and glucose concentrations.

  20. Pharmacokinetics of Two Alkaloids after Oral Administration of Rhizoma Coptidis Extract in Normal Rats and Irritable Bowel Syndrome Rats

    Directory of Open Access Journals (Sweden)

    Zipeng Gong

    2014-01-01

    Full Text Available A comparative pharmacokinetic study of berberine and palmatine after oral administration of Rhizoma Coptidis extract (96 mg/kg, containing berberine 22 mg/kg and palmatine 5 mg/kg based on body weight was performed in normal and postinflammation irritable bowel syndrome (PI-IBS rats, induced by intracolonic instillation of acetic acid and restraint stress. Quantification of berberine and palmatine in rat plasma was achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were collected at 13 different time points and the pharmacokinetic parameters were analyzed by WinNonlin software. The significant differences in the pharmacokinetic behaviors, such as Cmax⁡, AUC(0–t, Vd/F, and CL/F, of berberine and palmatine were found between normal and PI-IBS model rats. The results indicated that PI-IBS pathological conditions in rats could alter the pharmacokinetic behavior of drug. Preclinical pharmacokinetic studies are usually carried out on healthy animals. However, we should pay more attention to the fact that the change of pharmacokinetic behavior plays an important role on efficacy. It is essential to investigate the pharmacokinetics of the drug in disease status.

  1. Pharmacokinetics of Two Alkaloids after Oral Administration of Rhizoma Coptidis Extract in Normal Rats and Irritable Bowel Syndrome Rats

    Science.gov (United States)

    Gong, Zipeng; Chen, Ying; Zhang, Ruijie; Wang, Yinghan; Yang, Qing; Guo, Yan; Weng, Xiaogang; Gao, Shuangrong; Wang, Hailin; Zhu, Xiaoxin; Dong, Yu; Li, Yujie; Wang, Yajie

    2014-01-01

    A comparative pharmacokinetic study of berberine and palmatine after oral administration of Rhizoma Coptidis extract (96 mg/kg, containing berberine 22 mg/kg and palmatine 5 mg/kg based on body weight) was performed in normal and postinflammation irritable bowel syndrome (PI-IBS) rats, induced by intracolonic instillation of acetic acid and restraint stress. Quantification of berberine and palmatine in rat plasma was achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were collected at 13 different time points and the pharmacokinetic parameters were analyzed by WinNonlin software. The significant differences in the pharmacokinetic behaviors, such as C max⁡, AUC(0–t), V d/F, and CL/F, of berberine and palmatine were found between normal and PI-IBS model rats. The results indicated that PI-IBS pathological conditions in rats could alter the pharmacokinetic behavior of drug. Preclinical pharmacokinetic studies are usually carried out on healthy animals. However, we should pay more attention to the fact that the change of pharmacokinetic behavior plays an important role on efficacy. It is essential to investigate the pharmacokinetics of the drug in disease status. PMID:25309613

  2. Development of determination of four analytes of Zhi-Shao-San decoction using LC-MS/MS and its application to comparative pharmacokinetics in normal and irritable bowel syndrome rat plasma.

    Science.gov (United States)

    Chen, Jiayi; Chen, Zhi; Ma, Li; Liang, Qiaowen; Jia, Wei; Pan, Zhenzhen; Zeng, Yuaner; Jiang, Bin

    2014-10-01

    Zhi-Shao-San (ZSS), a traditional Chinese medicinal prescription, has been clinically used for the treatment of irritable bowel syndrome (IBS) for centuries. A comparative study was designed and conducted to compare the pharmacokinetic differences between paeoniflorin naringin, hesperidin and neohesperidin after oral administration of ZSS decoction to normal rats and IBS rats induced by acetic acid and restraint stress. Further, an efficient, sensitive and selective liquid chromatography/tandem mass spectrometry for the simultaneous determination of four analytes of ZSS decoction in rat plasma was developed and validated. The validated method was successfully applied to comparison of pharmacokinetic profiles of analytes in rat plasma. The results showed that the absorptions of naringin, hesperidin and neohesperidin in IBS group were all significantly higher than those in normal group and no obvious difference was seen for paeoniflorin between the two groups, which is helpful for improving clinical therapeutic efficacy and further pharmacological studies of ZSS.

  3. Plasma Pharmacokinetics and Routes of Excretion of [14C]-Labeled Arruva, a High-Potency Sweetener, Following Oral Administration to Beagle Dogs.

    Science.gov (United States)

    Casterton, Phillip L; Crincoli, Christine M; Brathwaite, Witty A; Rihner, Marisa O; Nikiforov, Andrey I; Thomas, Jennifer A

    2014-05-01

    [(14)C]-Labeled arruva [sodium/potassium (2R,4R)-2-amino-4-carboxy-4-hydroxy-5-(3-indolyl) pentanoate] was administered as a single gavage dose (10 mg/kg bw) to male and female Beagle dogs and 1 bile duct-cannulated male. The mean peak arruva plasma concentration equivalent of 1.2 µg/g occurred at first sampling time point of 1 hour postdosing. The mean area under the concentration versus time curve from 0 hour postdosing to the last time point was approximately 20 µg·h/g and the mean terminal plasma elimination half-life ranged from 15 hours in females to 21 hours in males. Over 168 hours postdosing, 35% to 50% of the administered arruva was eliminated in the urine with 44% to 53% eliminated in feces; 1.3% of the administered dose was recovered in bile. Arruva and its derivatives were identified using tandem mass spectrometry, and the relative percentage of each substance was quantified via radio high-performance liquid chromatography. Over a 168-hour collection period, combined urine and feces extract data from the 6 noncannulated dogs showed that approximately 91% of the dose was excreted as unchanged parent arruva (41% in urine and 50% in feces). In the cannulated male, 95.3% was excreted as unchanged parent arruva; 50.2% in urine, 43.9% in feces, and 1.3% in bile. Lactone and lactam derivatives of arruva and 1 unidentified substance were detected in urine only during the first 24 hours postdosing with the greatest amounts detected during the first 6 hours of collection; up to 1% of lactone or lactam derivatives were detected in bile samples. Plasma pharmacokinetics data indicated rapid absorption of arruva with the majority of radioactivity located in the feces collected in the first 48 hours.

  4. Simultaneous determination of asenapine and valproic acid in human plasma using LC-MS/MS:Application of the method to support pharmacokinetic study

    Institute of Scientific and Technical Information of China (English)

    Ambavaram Vijaya Bhaskar Reddy; Nandigam Venugopal; Gajulapalle Madhavin

    2013-01-01

    Combination of asenapine with valproic acid received regulatory approval for acute treatment of schizophrenia and maniac episodes of bipolar disorders. A simple LC-MS/MS method was developed and validated for simultaneous quantification of asenapine and valproic acid in human plasma. Internal standards were added to 300μL of plasma sample prior to liquid-liquid extraction using methyl tertiary butyl ether (MTBE). Chromatographic separation was achieved on Phenomenex C18 column (50 mm ? 4.6 mm, 5μm) in isocratic mode at 40 1C. The mobile phase used was 10 mM ammonium formate-acetonitrile (5:95, v/v) at a constant flow rate of 0.8 mL/min monitored on triple quadrupole mass spectrometer, operating in the multiple reaction monitoring (MRM) mode. The injection volume used for LC-MS/MS analysis was 15μL and the run time was 2.5 min. These low run time and small injection volume suggest the high efficiency of the proposed method. The method was validated over the concentration range of 0.1-10.02 ng/mL and 10-20,000 ng/mL for asenapine and valproic acid respectively. The method recoveries of asenapine (81.33%), valproic acid (81.70%), gliclazide (78.45%) and benzoic acid (79.73) from spiked plasma samples were consistent and reproducible. The application of this method was demonstrated by a pharmacokinetic study in 8 healthy male volunteers with 5 mg asenapine and 250 mg valproic acid administration.

  5. Simultaneous determination of six flavonoids from Paulownia tomentosa flower extract in rat plasma by LC-MS/MS and its application to a pharmacokinetic study.

    Science.gov (United States)

    Dai, Bin; Hu, Zhiqiang; Li, Haiyan; Yan, Chong; Zhang, Liwei

    2015-01-26

    A simple, rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous determination of six components including apigenin, quercetin, apigenin-7-O-β-D-glucoside, quercetin-3-O-β-D-glucoside, 3'-methoxyluteolin-7-O-β-D-glucoside, and tricin-7-O-β-D-glucopyranoside in rat plasma using formononetin as the internal standard (IS). The plasma samples were pretreated by a one-step liquid-liquid extraction with dichloromethane. The chromatographic separation was carried out on a ZORBAX SB-Aq column with a gradient mobile phase consisting of acetonitrile and 2mM aqueous ammonium acetate. All analytes and IS were quantitated through electrospray ionization in negative ion multiple reaction monitoring mode. The mass transitions were as follows: m/z 269.1→117.2 for apigenin, m/z 301.2→151.2 for quercetin, m/z 431.3→311.2 for apigenin-7-O-β-D-glucoside, m/z 463.2→300.2 for quercetin-3-O-β-D-glucoside, m/z 461.3→283.1 for 3'-methoxyluteolin-7-O-β-D-glucoside, m/z 491.3→313.1 for tricin-7-O-β-D-glucopyranoside, and m/z 267.2→252.2 for IS, respectively. All calibration curves exhibited good linearity with correlation coefficient (r)>0.995. The intra-day and inter-day precisions (RSD) at three QC levels were both less than 14.0% and the accuracies ranged from 89.8% to 113.8%. The extraction recoveries of six compounds ranged from 82.3% to 92.5%. The validated method was successfully applied to pharmacokinetic study of the six components in male rat plasma after oral administration of Paulownia tomentosa flower extract.

  6. A cancer research UK pharmacokinetic study of BPA-mannitol in patients with high grade glioma to optimise uptake parameters for clinical trials of BNCT

    Energy Technology Data Exchange (ETDEWEB)

    Cruickshank, G.S. [University of Birmingham and University Hospital Birmingham, Birmingham (United Kingdom)], E-mail: garth.cruickshank@uhb.nhs.uk; Ngoga, D.; Detta, A.; Green, S.; James, N.D.; Wojnecki, C.; Doran, J.; Hardie, J.; Chester, M.; Graham, N.; Ghani, Z. [University of Birmingham and University Hospital Birmingham, Birmingham (United Kingdom); Halbert, G.; Elliot, M.; Ford, S. [CR-UK Formulation Unit, University of Strathclyde, Glasgow (United Kingdom); Braithwaite, R.; Sheehan, T.M.T. [Regional Laboratory for Toxicology, Sandwell and West Birmingham Hospitals Trust, Birmingham (United Kingdom); Vickerman, J.; Lockyer, N. [Surface Analysis Research Centre, University of Manchester, Manchester (United Kingdom); Steinfeldt, H.; Croswell, G. [CR-UK Drug Development Office, London (United Kingdom)] (and others)

    2009-07-15

    This paper describes results to-date from a human pharmacokinetic study which began recruitment in December 2007. Results are presented for a single patient recruited in December 2007. A second patient was recruited in July 2008 but detailed data are not available at the time of writing. The trial is an open-label, non-comparative, non-therapeutic study of BPA-mannitol in patients with high-grade glioma, who will be undergoing stereotactic brain biopsy as part of the diagnostic process before definitive treatment. The study investigates the route of infusion (intra-venous (IV) or intra-carotid artery) and in each case will assess the effect of administration of mannitol as a blood-brain barrier disrupter. All cohorts will receive a 2 h infusion of BPA-mannitol, and for some cohorts an additional mannitol bolus will be administered at the beginning of this infusion. Measurements are made by inductively coupled plasma mass spectrometry (ICP-MS) of {sup 10}B concentration in samples of blood, urine, extra-cellular fluid in normal brain (via a dialysis probe), brain tissue around tumour and tumour tissue. Additional analysis of the tumour tissue is performed using secondary ion mass spectrometry (SIMS). The first patient was part of the cohort having intra-venous infusion without mannitol bolus. No serious clinical problems were experienced and the assay results can be compared with available patient data from other BNCT centres. In particular we note that the peak {sup 10}B concentration in blood was 28.1 mg/ml for a total BPA administration of 350 mg/kg which is very consistent with the previous experience with BPA-fructose reported by the Helsinki group.

  7. 阿克拉霉素A聚乳酸毫微粒冻干针剂在兔体内的血浆药动学研究%Study on Pharmacokinetics of Aclacinomycin A Polylactide Lyophilized Nanoparticle in Plasma of Rabbit

    Institute of Scientific and Technical Information of China (English)

    何林; 蒋学华

    2001-01-01

    OBJECTIVE:To study the pharmacokinetics of aclacinomycin A polylactide lyophilized nanopartical (ACM-A-PLA-NP) in plasma of rabbit.METHODS:HPLC was selected to determine the concentration of aclacinomycin A in plasma after a single dose of ACM-A-PLA-NP and lyophilized ACM-A.RESULTS:The pharmacokinetic parameters of these two dosage forms were obtained by 3p87.CONCLUSION:The lyophilized ACM-A-PLA-NP has a more sustained release character comparing with the lyophilized ACM-A.%目的:研究阿克拉霉素A聚乳酸毫微粒冻干针剂在兔体内的血浆药代动力学。方法:采用HPLC法测定给药后的血浆药物浓度。结果:经3p87药动学程序处理,得到两种制剂的药代动力学参数。结论:与阿克拉霉素A相比,阿克拉霉素A聚乳酸毫微粒具有显著的缓释特性。

  8. Absence of a pharmacokinetic interaction of rilpivirine with the P-glycoprotein substrate digoxin in healthy volunteers

    Directory of Open Access Journals (Sweden)

    H Crauwels

    2012-11-01

    Full Text Available Rilpivirine (RPV, TMC278, Edurant® is a next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI, which demonstrated high virologic response rates and non-inferiority versus efavirenz in two Phase III trials in HIV-infected patients through 96 weeks [1,2]. RPV has been shown to inhibit P-glycoprotein (P-gp in vitro with an apparent IC50 of 9.2 µM (3.4 µg/mL. This study evaluated the in-vivo effect of steady-state RPV 25 mg once daily (qd on the single-dose pharmacokinetics of the probe P-gp substrate digoxin. This was a Phase I, open-label, randomised, crossover trial in 22 HIV-negative volunteers. Participants received in one session a single 0.5 mg dose of digoxin, and in another session RPV 25 mg qd for 16 days with a single 0.5 mg dose of digoxin in the morning of Day 11. All study drugs were taken with a breakfast. Pharmacokinetic profiles of digoxin in plasma and urine were determined over 144 hours after dosing in each session. Steady-state RPV 24-hour pharmacokinetic profiles in plasma were determined on Day 11. Plasma and urine samples were analysed using validated LC-MS/MS methods. Pharmacokinetic parameters were calculated with non-compartmental methods. The least square (LS means and associated 90% confidence intervals (CI of treatment ratios were calculated based on log-transformed pharmacokinetic parameters. Safety and tolerability were assessed throughout the trial. Digoxin pharmacokinetic parameters and statistical results are summarised in Table 1. The plasma and urine digoxin pharmacokinetics were unaffected by co-administration of steady-state RPV. The 90% CIs of the LS means ratios of the main pharmacokinetic parameters were contained within the 0.80-1.25 boundaries of no effect. The terminal elimination half-life of digoxin was similar in the absence or the presence of steady-state RPV. RPV pharmacokinetic parameters were comparable to those in previous clinical trials in healthy volunteers. Administration

  9. Temporal evolution of the spectral lines emission and temperatures in laser induced plasmas through characteristic parameters

    Energy Technology Data Exchange (ETDEWEB)

    Bredice, F., E-mail: faustob@ciop.unlp.edu.ar [Centro de Investigaciones Ópticas, P.O. Box 3 C. P.1897 Gonnet, La Plata (Argentina); Pacheco Martinez, P. [Grupo de Espectroscopía Óptica de Emisión y Láser, Universidad del Atlántico, Barranquilla (Colombia); Sánchez-Aké, C.; Villagrán-Muniz, M. [Laboratorio de Fotofísica, Centro de Ciencias Aplicadas y Desarrollo Tecnológico, Universidad Nacional Autónoma de México, Apartado Postal 70-186, México D.F. 04510 (Mexico)

    2015-05-01

    In this work, we propose an extended Boltzmann plot method to determine the usefulness of spectral lines for plasma parameter calculations. Based on the assumption that transient plasmas are under ideal conditions during an specific interval of time Δt, (i.e. thin, homogeneous and in local thermodynamic equilibrium (LTE)), the associated Boltzmann plots describe a surface in the space defined by the coordinates X = Energy, Y = Time and Z = ln (λ{sub jl}I{sub j}/g{sub j}A{sub jl}), where I{sub j} is the integrated intensity of the spectral line, g{sub j} is the statistical weight of the level j, λ{sub jl} is the wavelength of the considered line and A{sub jl} is its transition rate. In order to express the Boltzmann plot surface in terms of a reduced set of constants B{sub i}, and δ{sub i}, we developed as a power series of time, the logarithm of I{sub n}(t)/I{sub n}(t{sub 0}), where I{sub n}(t) is the integrated intensity of any spectral line at time t, and I{sub n}(t{sub 0}) at initial time. Moreover, the temporal evolution of the intensity of any spectral line and consequently the temperature of the plasma can be also expressed with these constants. The comparison of the temporal evolution of the line intensity calculated using these constants with their experimental values, can be used as a criterion for selecting useful lines in plasma analysis. Furthermore, this method can also be applied to determine self-absorption or enhancement of the spectral lines, to evaluate a possible departure of LTE, and to check or estimate the upper level energy value of any spectral line. An advantage of this method is that the value of these constants does not depend on the spectral response of the detection system, the uncertainty of the transition rates belonging to the analyzed spectral lines or any other time-independent parameters. In order to prove our method, we determined the constants B{sub i} and δ{sub i} and therefore the Boltzmann plot surface from the temporal

  10. Simultaneous determination of imperatorin and its metabolite xanthotoxol in rat plasma and urine by LC-MS/MS and its application to pharmacokinetic studies.

    Science.gov (United States)

    Ngo, Lien; Tran, Phuong; Ham, Seong-Ho; Cho, Jung-Hee; Cho, Hea-Young; Lee, Yong-Bok

    2017-02-15

    An accurate, precise, selective, and sensitive liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of imperatorin (IMP) and its metabolite, xanthotoxol (XAN), in rat plasma and urine samples. The analytes, along with psoralen as an internal standard, were determined by multiple reaction monitoring (MRM) operated in the positive electrospray ionization (ESI) mode. Chromatographic separation was performed on an Acquity UPLC BEH C18 column (50mm×2.1mm, 1.7μm) with a mobile phase consisting of 0.1% formic acid solution and 0.1% formic acid in methanol at a flow rate of 0.3mL/min. The run time was 6min per sample and the injection volume was 5μL. The method had a lower limit of quantification (LLOQ) of 0.25ng/mL for IMP in plasma and urine, and 1ng/mL for XAN in urine. The linear calibration curves were fitted over the range of 0.25-1000ng/mL for IMP in plasma, 0.25-1000ng/mL for IMP in urine, and 1-1000ng/mL for XAN in urine, with correlation coefficients greater than 0.995. The inter- and intra-day accuracies (relative error, RE%) were between -8.5% and 3.5%, and the precisions (relative standard deviation, RSD%) were less than 10.0% for all quality control samples (QCs). The analytes were extracted from rat plasma and urine samples using a liquid-liquid extraction method with the extraction recovery in the range of 60.3-79.1%. A good stability of the analytes was observed in all the analysis procedures. The method was successfully validated and applied to determine the pharmacokinetics of IMP in rat plasma and, for the first time, the metabolite kinetics of IMP to XAN in rat urine after IMP administration.

  11. Simultaneous determination of nine lignans from Schisandra chinensis extract using ultra-performance liquid chromatography with tandem mass spectrometry in rat plasma, urine, and gastrointestinal tract samples: application to the pharmacokinetic study of Schisandra chinensis.

    Science.gov (United States)

    Kim, You-Jin; Lee, Hee Ju; Kim, Chul Young; Han, Sun-Young; Chin, Young-Won; Choi, Young Hee

    2014-10-01

    The fruit of Schisandra chinensis is a well-known herbal medicine and dietary supplement due to a variety of biological activities including antihepatotoxic and antihyperlipidemic activities. However, the simultaneous validation methodology and pharmacokinetic investigation of nine lignans of S. chinensis extract in biological samples have not been proved yet. Thus, the present study was undertaken to develop the proper sample preparation method and simultaneous analytical method of schisandrol A, gomisin J, schisandrol B, tigloylgomisin H, angeloylgomisin H, schisandrin A, schisandrin B, gomisin N, and schisandrin C in the hexane-soluble extract of S. chinensis to apply for the pharmacokinetic study in rats. All intra- and interprecisions of nine lignans were below 13.7% and accuracies were 85.1-115% and it is enough to evaluate the pharmacokinetic parameters after both intravenous and oral administration of hexane-soluble extract of S. chinensis to rats.

  12. Typical Profiles and Distributions of Plasma and Magnetic Field Parameters in Magnetic Clouds at 1 AU

    Science.gov (United States)

    Rodriguez, L.; Masías-Meza, J. J.; Dasso, S.; Démoulin, P.; Zhukov, A. N.; Gulisano, A. M.; Mierla, M.; Kilpua, E.; West, M.; Lacatus, D.; Paraschiv, A.; Janvier, M.

    2016-08-01

    Magnetic clouds (MCs) are a subset of interplanetary coronal mass ejections (ICMEs). They are important because of their simple internal magnetic field configuration, which resembles a magnetic flux rope, and because they represent one of the most geoeffective types of solar transients. In this study, we analyze their internal structure using a superposed epoch method on 63 events observed at L1 by the Advance Composition Explorer (ACE), between 1998 and 2006. In this way, we obtain an average profile for each plasma and magnetic field parameter at each point of the cloud. Furthermore, we take a fixed time-window upstream and downstream from the MC to also sample the regions preceding the cloud and the wake trailing it. We then perform a detailed analysis of the internal characteristics of the clouds and their surrounding solar wind environments. We find that the parameters studied are compatible with log-normal distribution functions. The plasma β and the level of fluctuations in the magnetic field vector are the best parameters to define the boundaries of MCs. We find that one third of the events shows a peak in plasma density close to the trailing edge of the flux ropes. We provide several possible explanations for this result and investigate if the density peak is of a solar origin ( e.g. erupting prominence material) or formed during the magnetic cloud travel from the Sun to 1 AU. The most plausible explanation is the compression due to a fast overtaking flow, coming from a coronal hole located to the east of the solar source region of the magnetic cloud.

  13. Validation and pharmacokinetic application of a high-performance liquid chromatographic technique for determining the concentrations of amodiaquine and its metabolite in plasma of patients treated with oral fixed-dose amodiaquine-artesunate combination in areas of malaria endemicity.

    Science.gov (United States)

    Adedeji, Olumuyiwa N; Bolaji, Oluseye O; Falade, Catherine O; Osonuga, Odusoga A; Ademowo, Olusegun G

    2015-09-01

    Artemisinin-based combination therapies (ACTs) have been adopted by most African countries, including Nigeria, as first-line treatments for uncomplicated falciparum malaria. Fixed-dose combinations of these ACTs, amodiaquine-artesunate (FDC AQAS) and artemether-lumefantrine (AL), were introduced in Nigeria to improve compliance and achieve positive outcomes of malaria treatment. In order to achieve clinical success with AQAS, we developed and validated a simple and sensitive high-performance liquid chromatography (HPLC) method with UV detection for determination of amodiaquine (AQ) and desethylamodiaquine (DAQ) in plasma using liquid-liquid extraction of the drugs with diethyl ether following protein precipitation with acetonitrile. Chromatographic separation was achieved using an Agilent Zorbax C18 column and a mobile phase consisting of distilled water-methanol (80:20 [vol/vol]) with 2% (vol/vol) triethylamine, pH 2.2, at a flow rate of 1 ml/min. Calibration curves in spiked plasma were linear from 100 to 1,000 ng/ml (r > 0.99) for both AQ and DAQ. The limit of detection was 1 ng (sample size, 20 μl). The intra- and interday coefficients of variation at 150, 300, and 900 ng/ml ranged from 1.3 to 4.8%, and the biases were between 6.4 and 9.5%. The mean extraction recoveries of AQ and DAQ were 80.0% and 68.9%, respectively. The results for the pharmacokinetic parameters of DAQ following oral administration of FDC AQAS (612/200 mg) for 3 days in female and male patients with uncomplicated falciparum malaria showed that the maximum plasma concentrations (C max) (740 ± 197 versus 767 ± 185 ng/ml), areas under the plasma concentration-time curve (AUC) (185,080 ± 20,813 versus 184,940 ± 16,370 h · ng/ml), and elimination half-life values (T 1/2) (212 ± 1.14 versus 214 ± 0.84 h) were similar (P > 0.05).

  14. Selenium, copper and zinc in seminal plasma of men with varicocele, relationship with seminal parameters.

    Science.gov (United States)

    Camejo, María Isabel; Abdala, Lyzeth; Vivas-Acevedo, Giovanny; Lozano-Hernández, Ricardo; Angeli-Greaves, Miriam; Greaves, Eduardo D

    2011-12-01

    Varicocele has been associated with decrease in seminal parameters. Selenium (Se), copper (Cu), and zinc (Zn) are trace elements essential for normal spermatogenesis of mammals and play a critical role as antioxidant defense system enzymes. Se, Cu, and Zn are associated with sperm quality in fertile and infertile men. However, there is little information about Se, Cu, and Zn concentrations in semen in patients with varicocele and its association with seminal parameters. The purpose of this study was to determine the concentrations of Se, Cu, and Zn in semen of patients with varicocele and the relationship with seminal parameters. Total Reflection X-Ray Fluorescence was used for the fist time in the seminal fluid analysis. The concentration of selenium in men with varicocele was smaller than the normozoospermic group, while no differences were observed for both concentrations of zinc and copper. A significant positive correlation between zinc and selenium concentration was observed. Selenium in seminal plasma correlates with a good spermatozoa concentrations, motility, and morphology. Additionally, a significant positive correlation was observed between zinc levels and sperm count. In conclusion, a decrease in selenium concentration was associated with detriment of seminal parameters. A study should be conducted to evaluate the benefits of both zinc and selenium supplementation to improve seminal parameters in patients with varicocele.

  15. Pharmacokinetics of single-dose doripenem in adults with cystic fibrosis.

    Science.gov (United States)

    Cirillo, Iolanda; Vaccaro, Nicole; Redman, Rebecca; Black, Philip L; Kearns, Gregory L

    2012-11-01

    The pharmacokinetics of doripenem and doripenem-M-1 (inactive metabolite) were evaluated in an open-label, 2-period, single-sequence study in which single 1-g and 2-g doses of doripenem were administered intravenously over 4 hours to adult patients with cystic fibrosis (CF). The systemic exposure to doripenem and doripenem-M-1, as measured by observed apparent maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC), increased approximately proportionally to the increase in dose. Other pharmacokinetic parameters of doripenem and doripenem-M-1, including clearance, volume of distribution, and elimination half-life, were similar for the 1-g and 2-g doses. The results from this study were also compared with those from a previous study in adult healthy volunteers (HVs) without CF, from a previously conducted pharmacokinetic study, who received single doses of 500 mg and 1 g doripenem administered over 4 hours. The pharmacokinetics of doripenem in adult patients with CF are similar to those from adult HVs, noting some differences in the disposition when comparing body mass index-adjusted pharmacokinetic parameters.

  16. Development of an LC/MS/MS method in order to determine arctigenin in rat plasma: its application to a pharmacokinetic study.

    Science.gov (United States)

    Zou, Quanfei; Gu, Yuan; Lu, Rong; Zhang, Tiejun; Zhao, Guang-Rong; Liu, Changxiao; Si, Duanyun

    2013-09-01

    In this study, a simple and sensitive LC/MS/MS method was developed and validated for the determination of arctigenin in rat plasma. The MS detection was performed using multiple reaction monitoring at the transitions of m/z 373.2 → 137.3 for arctigenin and m/z 187.1 → 131.0 for psoralen (internal standard) with a Turbo IonSpray electrospray in positive mode. The calibration curves fitted a good linear relationship over the concentration range of 0.2-500 ng/mL. It was found that arctigenin is not stable enough at both room temperature and -80 °C unless mixed with methanol before storage. The validated LC/MS/MS method was successfully applied for the pharmacokinetic study of arctigenin in rats. After intravenous injection of 0.3 mg/kg arctigenin injection to rats, the maximum concentration, half-life and area under the concentration-time curve were 323 ± 65.2 ng/mL, 0.830 ± 0.166 and 81.0 ± 22.1 h ng/mL, respectively.

  17. Simultaneous determination of two epimeric furofuran lignans (sesamin and asarinin) of Asarum heterotropoides extract in rat plasma by LC/MS/MS: application to pharmacokinetic study.

    Science.gov (United States)

    Ma, Yingyan; Xu, Kai; Wang, Shumin; Han, Yaling

    2014-09-01

    A rapid, sensitive and selective liquid chromatography-tandem mass spectrometry was developed to determine two epimeric furofuran lignans (sesamin and asarinin) simultaneously from Asarum heterotropoides extract in rat plasma. Simple protein precipitation with acetonitrile was performed to extract analytes by using alantolactone as an internal standard. Chromatographic separation was achieved using a DIKMA Diamonsil C18 analytical column (4.6 mm × 150 mm, i.d., 5 µm) by isocratically eluting with a mobile phase consisting of methanol/5 mM ammonium acetate/formic acid (75:25:0.1, v/v/v) at a flow rate of 0.8 mL/min. Tandem mass spectrometric detection with an electrospray ionization interface was performed by multiple reaction monitoring in positive ionization mode. This method was validated according to specificity, sensitivity, linearity, intra- and inter-day precision (sesamin and 5.00-3 000 ng/mL for asarinin. This method has been successfully applied in a pharmacokinetic study of A. heterotropoides extract containing sesamin and asarinin after this extract was orally administrated in rats.

  18. Development, validation of liquid chromatography-tandem mass spectrometry method for simultaneous determination of rosuvastatin and metformin in human plasma and its application to a pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    P Pavan Kumar

    2015-01-01

    Full Text Available A new, simple and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS method for simultaneous determination of rosuvastatin (ROS and metformin (MET in human plasma was developed. The assay procedure involved simple protein precipitation with acetonitrile. Following precipitation, fraction of supernatant was decanted and evaporated under gentle stream of nitrogen at 40΀C. The residue was reconstituted in mobile phase and injected. The chromatographic separation was achieved with Thermo Hypurity C18 column (50 mm Χ 4.6 mm, 5 μ using a mobile phase composition containing 0.1% v/v formic acid in water and acetonitrile (30:70, v/v at a flow rate of 0.4 mL/min. The total run time was 3.5 min. The method showed good linearity in the range 0.5-200 ng/mL for ROS and 2-2000 ng/mL for MET with correlation coefficient (r >0.9994 for both the analytes. The intra and inter-day precision values for ROS and MET met the acceptance criteria as per regulatory guidelines. The battery of stability studies viz., bench-top, freeze-thaw and long term stability were performed. The developed method was applied to a pharmacokinetic study.

  19. Simultaneous determination of morniflumate and its major active metabolite, niflumic acid, in human plasma by high-performance liquid chromatography in stability and pharmacokinetic studies.

    Science.gov (United States)

    Cho, Hea-Young; Park, Geun-Kyeong; Lee, Yong-Bok

    2013-11-01

    A rapid, sensitive and stable high-performance liquid chromatography (HPLC) method was developed and validated for the simultaneous determination of morniflumate and its major active metabolite, niflumic acid, in human plasma. HPLC analysis was carried out using a 5 µm particle size, C18 -bonded silica column with a mixture of acetonitrile and 0.005 m potassium phosphate monobasic in water (60:40, v/v) as the mobile phase and UV detection at 287 nm. The method involved the treatment with 50 μL of 0.4 m hydrochloric acid for the stability of morniflumate, extraction with diethylether and evaporation to dryness under a nitrogen stream. The lower limit of quantitation for morniflumate and niflumic acid was 50 and 500 ng/mL, respectively. The calibration curves for morniflumate and niflumic acid were linear over the concentration range of 50-20,000 ng/mL and 500-50,000 ng/mL, respectively, with correlation coefficients greater than 0.9995 and inter- or intra-batch coefficients of variation not exceeding 13.79%. The variability (percentage difference) of incurred sample re-analysis did not exceed 11.72% and all of the repeat samples fell within 20% of the mean value. This assay procedure was applied successfully to an examination of the pharmacokinetics of morniflumate and its metabolite, niflumic acid, in human subjects.

  20. Rapid high performance liquid chromatographic method for determination of clarithromycin in human plasma using amperometric detection: application in pharmacokinetic and bioequivalence studies.

    Science.gov (United States)

    Foroutan, Seyed Mohsen; Zarghi, Afshin; Shafaati, Alireza; Madadian, Babak; Abolfathi, Farshid

    2013-01-01

    A rapid, sensitive and reproducible HPLC method using amperometric detector was developed and validated for the analysis of clarithromycin in human plasma. The separation was achieved on a monolithic silica column (MZ- C8 125×4.0 mm) using acetonitrile-methanol-potassium dihydrogen phosphate buffer (40:6:54,v/v), with pH of 7.5, as the mobile phase at a flow rate of 1.5 mL/min. The assay enables the measurement of clarithromycin for therapeutic drug monitoring with a minimum quantification limit of 20 ng/mL. The method involves simple, protein precipitation procedure and analytical recovery was complete. The calibration curve was linear over the concentration range of 0.1-6 μg/mL. The coefficients of variation for inter-day and intra-day assay were found to be less than 6%. This method was used in bioequivalency and pharmacokinetic studies of the test (generic) product 2 × 500 mg clarithromycin tablets, with respect to the reference product.

  1. Simultaneous determination of ambroxol and salbutamol in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.

    Science.gov (United States)

    Guo, Zhening; Chen, Yangsheng; Ding, Xiaoliang; Huang, Chenrong; Miao, Liyan

    2016-11-01

    A rapid, selective and sensitive liquid chromatography-tandem mass spectrometry assay method was developed for simultaneous determination of ambroxol and salbutamol in human plasma using citalopram hydrobromide as internal standard (IS). The sample was alkalinized with ammonia water (33:67, v/v) and extracted by single liquid-liquid extraction with ethyl acetate. Separation was achieved on Waters Acquity UPLC BEH C18 column using a gradient program at a flow rate of 0.2 mL/min. Detection was performed using electrospray ionization in positive ion multiple reaction monitoring mode by monitoring the ion transitions m/z 378.9 → 263.6 (ambroxol), m/z 240.2 → 147.7 (salbutamol) and m/z 325.0 → 261.7 (IS). The total analytical run time was relatively short (3 min). Calibration curves were linear in the concentration range of 0.5-100.0 ng/mL for ambroxol and 0.2-20.0 ng/mL for salbutamol, with intra- and inter-run precision (relative standard deviation) salbutamol. The method was successfully applied in a clinical pharmacokinetic study of the compound ambroxol and salbutamol tablets.

  2. Development and validation of amisulpride in human plasma by HPLC coupled with tandem mass spectrometry and its application to a pharmacokinetic study.

    Science.gov (United States)

    Mogili, Ramakotaiah; Kanala, Kanchanamala; Challa, Balasekhara Reddy; Chandu, Babu Rao; Bannoth, Chandrasekhar Kottapalli

    2011-09-01

    In this study, authors developed a simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantification of Amisulpride in human plasma using Amisulpride-d(5) as an internal standard (IS). Chromatographic separation was performed on Zorbax Bonus-RP C18, 4.6 × 75 mm, 3.5 μm column with an isocratic mobile phase composed of 0.2% formic acid:methanol (35:65 v/v), at a flow-rate of 0.5 mL/min. Amisulpride, Amisulpride-d(5) was detected at m/z 370.1→242.1 and 375.1→242.1. The drug and the IS were extracted by a liquid-liquid extraction method. The method was validated over a linear concentration range of 2.0-2500.0 ng/mL for Amisulpride with a correlation coefficient of (r(2)) ≥ 0.9982. This method demonstrated intra- and inter-day precision within 0.9 to 1.7 and 1.5 to 2.8 % and intra- and inter-day accuracy within 98.3 to 101.5 and 96.0 to 101.0 % for Amisulpride. Amisulpride was found to be stable at 3 freeze-thaw cycles, bench top and auto sampler stability studies. The developed method was successfully applied to a pharmacokinetic study.

  3. Simultaneous determination of pirfenidone and its metabolite in human plasma by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study.

    Science.gov (United States)

    Wen, Yu-Guan; Liu, Xia; He, Xiu-Ling; Shang, De-Wei; Ni, Xiao-Jia; Zhang, Ming; Wang, Zhan-Zhang; Hu, Jin-Qing; Qiu, Chang

    2014-01-01

    A simple and rapid analytical method for the simultaneous determination of pirfenidone and its metabolite, 5-carboxy-pirfenidone, in human plasma using liquid chromatography-tandem mass spectrometry has been developed and validated. Aliquots of plasma (0.1 mL) containing pirfenidone and 5-carboxy-pirfenidone, as well as deuterium-labeled internal standards (ISs), were deproteinized using acetonitrile. An Agilent Zorbax Plus C18 column was used for the chromatography, with isocratic elution. The mobile phase was a mixture of acetonitrile and aqueous ammonium formate solution (5 mM) containing 0.1% formic acid (60 : 40, v/v). Using multiple reaction monitoring in positive ionization mode, transitions m/z 186.1 → 65.1, m/z 216.0 → 77.0, m/z 191.1 → 65.1 and m/z 221.0 → 81.0 were chosen to quantify pirfenidone, 5-carboxy-pirfenidone and the two ISs, respectively. The time of analysis was pirfenidone, and 0.005-15 μg/mL for 5-carboxy-pirfenidone. The lower limit of quantification for both analytes was 0.005 μg/mL. The intra- and interday precision and relative errors in quality control samples were between -11.7 and 1.3% for pirfenidone and between -5.6 and 2.5% for 5-carboxy-pirfenidone, with mean recoveries ≥90%. The method that has been developed is easy to carry out, sensitive and rapid, and has been successfully used to investigate the pharmacokinetics of pirfenidone in healthy human volunteers.

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

    Science.gov (United States)

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

    2017-04-01

    Levo-tetrahydropalmatine (l-THP) is an alkaloid isolated from Chinese medicinal herbs of the Corydalis and Stephania genera. It has been used in China for more than 40 years mainly as an analgesic with sedative/hypnotic effects. Despite its extensive use, its metabolism has not been quantitatively studied, nor there a sensitive reliable bioanalytical method for its quantification simultaneously with its metabolites. As such, the objective of this study was to develop and validate a sensitive and selective HPLC method for simultaneous quantification of l-THP and its desmethyl metabolites l-corydalmine (l-CD) and l-corypalmine (l-CP) in rat plasma and brain tissues. Rat plasma and brain samples were processed by liquid-liquid extraction using ethyl acetate. Chromatographic separation was achieved on a reversed-phase Symmetry® C18 column (4.6 × 150 mm, 5 μm) at 25°C. The mobile phase consisted of acetonitrile-methanol-10 mm ammonium phosphate (pH 3) (10:30:60, v/v) and was used at a flow rate of 0.8 mL/min. The column eluent was monitored at excitation and emission wavelengths of 230 and 315 nm, respectively. The calibration curves were linear over the concentration range of 1-10,000 ng/mL. The intra- and interday reproducibility studies demonstrated accuracy and precision within the acceptance criteria of bioanalytical guidelines. The validated HPLC method was successfully applied to analyze samples from a pharmacokinetic study of l-THP in rats. Taken together, the developed method can be applied for bioanalysis of l-THP and its metabolites in rodents and potentially can be transferred for bioanalysis of human samples.

  5. Simultaneous determination of harpagoside and cinnamic acid in rat plasma by liquid chromatography electrospray ionization mass spectrometry and its application to pharmacokinetic studies.

    Science.gov (United States)

    Wang, Su-Jun; Ruan, Jin-Xiu; Zhao, Yan-Hong; Zhang, Zhen-Qing

    2008-01-01

    A simple and sensitive method was developed for the simultaneous quantification of harpagoside and cinnamic acid in rat plasma using high-performance liquid chromatography system coupled to a negative ion electrospray mass spectrometric analysis. The plasma sample preparation was a simple deproteinization by the addition of two volumes of acetonitrile. The analytes were separated on an Intersil C8-3 column (2.1 mm i.d.x250 mm, 5 microm) with acetonitrile-5 mm ammonium formate aqueous solution (60:40, v/v) as mobile phase at a flow-rate of 0.2 mL/min. Detection was performed on a quadrupole mass spectrometer equipped with electrospray ionization (ESI) source operated under selected ion monitoring (SIM) mode. [M+HCOO]- at m/z 539 for harpagoside, [M-H]- at m/z 147 for cinnamic acid and [M-H]- at m/z 137 for salylic acid (internal standard) were selected as detecting ions, respectively. The method was validated over the concentration range 7-250 ng/mL for harpagoside and 5-500 ng/mL for cinnamic acid. The lower limits of quantitation for harpagoside and cinnamic acid were 7 and 5 ng/mL, respectively. The intra- and inter-day precisions (RSD%) were within 9.5% and the assay accuracies (RE%) ranged from -5.3 to 3.0% for both analytes. Their average recoveries were greater than 86%. Both analytes were proved to be stable during all sample storage, preparation and analysis procedures. The method was successfully applied to the pharmacokinetic study of harpagoside and cinnamic acid following oral administration of Radix Scrophulariae extract to rats.

  6. Development and validation of a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of acrivastine and pseudoephedrine in human plasma and its application in pharmacokinetics.

    Science.gov (United States)

    He, J-C; Feng, E-F; Liu, M; Li, H-L; Tian, M; Zhang, Q; Dong, L-C; Xu, G-L

    2012-10-01

    A specific, sensitive and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the simultaneous determination of acrivastine and pseudoephedrine in human plasma samples. Plasma samples were processed and analyzed on a Phenomenex Luna 3 μ CN 100A column (150 mm×2.0 mm) eluted with the mobile phase consisting of methanol and 0.01 mol/L ammonium acetate water solution containing 0.1% formic acid (45:55, v/v) at a flow rate of 0.2 mL/min. The analytes were detected by positive ion electrospray ionization in multiple reaction monitoring mode. The transitions of m/z 349→278, m/z 166→148 and m/z 256→167 were monitored for acrivastine, pseudoephedrine and diphenhydramine (IS), respectively. The method was specific and sensitive with a lower limit of quantitation (LLOQ) of 1.52 ng/mL for acrivastine and 8.13 ng/mL for pseudoephedrine. The method showed good linearity in the range of 1.52~606.0 0 ng/mL for acrivastine and 8.13~813.12 ng/mL for pseudoephedrine (r≥0.996). The mean recovery were ranged 91.82% ~ 98.46% for acrivastine and 90.77% ~ 92.05% for pseudoephedrine. Validation results, such as accuracy, precision and repeatability were within the required limits. The method was successfully applied in a pharmacokinetic study of the acrivastine and pseudoephedrine hydrochloride compound capsule in humans.

  7. Influence of geometrical parameters on performance of plasma synthetic jet actuator

    Science.gov (United States)

    Zong, Hao-hua; Wu, Yun; Jia, Min; Song, Hui-min; Liang, Hua; Li, Ying-hong; Zhang, Zhi-bo

    2016-01-01

    Plasma synthetic jet actuator (PSJA) has shown wide and promising application prospects in a high speed flow control field, due to its rapid response, high exhaust velocity, and non-moving components. In this paper, the total pressure profile of a plasma synthetic jet (PSJ) is measured and a new method is developed to evaluate the pulsed thrust of the PSJA. The influence of geometrical parameters including the electrode distance, the orifice diameter, and the throat length on PSJA performance is analyzed based on the pulsed thrust, the discharge characteristics, and the schlieren images. When varying the electrode distance, the dominant factor determining the jet intensity is the heating volume instead of the discharge energy. For the arc discharge, the electrode distance should be extended to increase both the jet velocity and the jet duration time. The design of the orifice diameter should be based on the controlled flow field. A large orifice diameter produces a strong perturbation with short time duration, while a small orifice diameter induces a lasting jet with low mass flux. In order to obtain better high frequency performance, the throat length should be shortened on the condition that the structural strength of the PSJA is maintained, while there is almost no influence of the throat length on the single cycle performance of the PSJA. Once the discharge energy is fixed, the pulsed thrust remains almost unchanged with different orifice diameters and throat lengths. These three geometrical parameters are independent to some extent and can be optimized separately.

  8. Plasma arc cutting optimization parameters for aluminum alloy with two thickness by using Taguchi method

    Science.gov (United States)

    Abdulnasser, B.; Bhuvenesh, R.

    2016-07-01

    Manufacturing companies define the qualities of thermal removing process based on the dimension and physical appearance of the cutting material surface. The surface roughness of the cutting area for the material and the material removal rate being removed during the manual plasma arc cutting process were importantly considered. Plasma arc cutter machine model PS-100 was used to cut the specimens made from aluminium alloy 1100 manually based on the selected parameters setting. Two different thicknesses of specimens, 3mm and 6mm were used. The material removal rate (MRR) was measured by determining the difference between the weight of specimens before and after the cutting process. The surface roughness (Ra) was measured by using MITUTOYO CS-3100 machine and analysis was conducted to determine the average roughness (Ra) value, Taguchi method was utilized as an experimental layout to obtain MRR and Ra values. The results indicate that the current and cutting speed is the most significant parameters, followed by the arc gap for both rate of material removal and surface roughness.

  9. Performance Testing of Suspension Plasma Sprayed Thermal Barrier Coatings Produced with Varied Suspension Parameters

    Directory of Open Access Journals (Sweden)

    Nicholas Curry

    2015-07-01

    Full Text Available Suspension plasma spraying has become an emerging technology for the production of thermal barrier coatings for the gas turbine industry. Presently, though commercial systems for coating production are available, coatings remain in the development stage. Suitable suspension parameters for coating production remain an outstanding question and the influence of suspension properties on the final coatings is not well known. For this study, a number of suspensions were produced with varied solid loadings, powder size distributions and solvents. Suspensions were sprayed onto superalloy substrates coated with high velocity air fuel (HVAF -sprayed bond coats. Plasma spray parameters were selected to generate columnar structures based on previous experiments and were maintained at constant to discover the influence of the suspension behavior on coating microstructures. Testing of the produced thermal barrier coating (TBC systems has included thermal cyclic fatigue testing and thermal conductivity analysis. Pore size distribution has been characterized by mercury infiltration porosimetry. Results show a strong influence of suspension viscosity and surface tension on the microstructure of the produced coatings.

  10. Relevant parameter space and stability of spherical tokamaks with a plasma center column

    Science.gov (United States)

    Lampugnani, L. G.; Garcia-Martinez, P. L.; Farengo, R.

    2017-02-01

    A spherical tokamak (ST) with a plasma center column (PCC) can be formed inside a simply connected chamber via driven magnetic relaxation. From a practical perspective, the ST-PCC could overcome many difficulties associated with the material center column of the standard ST reactor design. Besides, the ST-PCC concept can be regarded as an advanced helicity injected device that would enable novel experiments on the key physics of magnetic relaxation and reconnection. This is because the concept includes not only a PCC but also a coaxial helicity injector (CHI). This combination implies an improved level of flexibility in the helicity injection scheme required for the formation and sustainment phases. In this work, the parameter space determining the magnetic structure of the ST-PCC equilibria is studied under the assumption of fully relaxed plasmas. In particular, it is shown that the effect of the external bias field of the PCC and the CHI essentially depends on a single parameter that measures the relative amount of flux of these two entities. The effect of plasma elongation on the safety factor profile and the stability to the tilt mode are also analyzed. In the first part of this work, the stability of the system is explained in terms of the minimum energy principle, and relevant stability maps are constructed. While this picture provides an adequate insight into the underlying physics of the instability, it does not include the stabilizing effect of line-tying at the electrodes. In the second part, a dynamical stability analysis of the ST-PCC configurations, including the effect of line-tying, is performed by numerically solving the magnetohydrodynamic equations. A significant stability enhancement is observed when the PCC contains more than the 70% of the total external bias flux, and the elongation is not higher than two.

  11. The Effect of Silibinin on the Pharmacokinetics of Ivabradine and N-Desmethylivabradine in Rats.

    Science.gov (United States)

    Chen, Xing-Peng; Zheng, Hai-Tao; Cai, Wei-Wei; Li, Meng-Ke; Zhang, Jian-Wei; Hu, Jie

    2015-01-01

    The objective of this work was to investigate the effect of orally administered silibinin on the pharmacokinetics of ivabradine and its active metabolite N-desmethylivabradine in rats. Twelve healthy male Sprague-Dawley rats were randomly divided into 2 groups: the control group (received oral 1.0 mg/kg ivabradine alone) and the combination group (1.0 mg/kg ivabradine orally coadministered with 30 mg/kg silibinin). The plasma concentration of ivabradine and N-desmethylivabradine were estimated by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) and different pharmacokinetic parameters were calculated using the DAS 2.0 software. The pharmacokinetic parameters of t1/2, Cmax, AUC(0-t) and AUC(0-∞) of ivabradine in the combination group were significantly higher than those in the control group (p ivabradine. Henceforth, the pharmacodynamic influence of this interaction should be taken into consideration while prescribing ivabradine to patients already taking silibinin.

  12. LC-MS法测定大鼠血浆中利可君的浓度及其药动学研究%Determination of Leucogen Concentration in Rats Plasma by LC-MS and Its Pharmacokinetic Study

    Institute of Scientific and Technical Information of China (English)

    赵国珍; 张朝晖; 谢少斐

    2013-01-01

    目的:建立测定大鼠血浆中利可君浓度的方法,并研究其药动学.方法:取大鼠尾静脉注射利可君1 mg/kg和灌胃利可君10 mg/kg(n=6),采用液质联用(LC-MS)法,以替硝唑为内标,检测给药前和给药后10、20、30、40、60、90、120、180、240、360、1 440min的血药浓度,并用DAS 2.0软件计算药动学参数.液相色谱条件:色谱柱为Agilent Zorbax Eclipse plusC18,流动相为乙腈-水-冰醋酸(20∶80∶0.3),梯度洗脱;质谱条件:电喷雾离子源,利可君和替硝唑的选择检测离子质荷比分别为296.1[M+H]+、248.1 [M+H]+.结果:利可君检测质量浓度的线性范围为0.048~30 μg/ml(r=0.999 3),定量限为0.048 μg/ml;尾静脉注射、灌胃后的药动学参数分别为cmax:(1.51±0.66)、(17.78±2.67) μg/ml,t1/2:(1.23±0.85)、(0.88±0.23)h,AUC0-∞:(1.29±0.56)、(9.87±0.47) μg·h/ml.结论:本方法准确可靠、检测灵敏,适用于利可君的血药浓度测定;利可君在大鼠体内药动学符合一室模型.%OBJECTIVE:To develop a method for the determination of leucogen in rat plasma,and to study its pharmacokinetics.METHODS:Rats were given leucogen 1 mg/kg by tail intravenous administration and leucogen 10 mg/kg by intragastric administration (n=6).Using tinidazole as internal standard,LC-MS method was used to detect the plasma concentration of leucogen before and 10,20,30,40,60,90,120,180,240,360,1 440 min after medication; pharmacokinetic parameters were calculated with DAS 2.0 software.The determination was performed on a Agilent Zorbax Eclipse plus C18 column with mobile phase consisted of acetonitrile-water-acetic acid (20 ∶ 80 ∶ 0.3) for gradient elution.MS condition:ESI,296.1 [M+H]+ for leucogen,248.1[M+H]+for tinidazole.RESULTS:The linear range of leucogen were 0.048-30 μg/ml (r=0.999 3).The limit of quantification of leucogen was 0.048 μg/ml.Pharmacokinetic parameters of leucogen after tail intravenous administration vs.intragastric administration

  13. Pharmacokinetics of tulathromycin after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus).

    Science.gov (United States)

    Clothier, K A; Leavens, T; Griffith, R W; Wetzlich, S E; Baynes, R E; Riviere, J E; Tell, L A

    2011-10-01

    Tulathromycin, a novel triamilide in the macrolide class, is labeled for treatment of bacterial pneumonia in cattle and swine. This manuscript evaluates pharmacokinetics of tulathromycin in goats. In two different studies, six juvenile and ten market-age goats received a single injection of 2.5 mg/kg of tulathromycin subcutaneously; in a third study, 18 juvenile goats were treated with 2.5, 7.5, or 12.5 mg/kg tulathromycin weekly with three subcutaneous injections. Pharmacokinetic parameters estimated from the plasma concentrations from single injections were similar between the two groups of goats and to previously reported parameters in cattle and swine. Mean terminal half-lives were 59.1 ± 7.6 and 61.2 ± 8.7 h for juvenile and market-age goats, respectively. In the multi-dose study, pharmacokinetic parameters estimated from plasma concentrations demonstrated significant differences at P < 0.05 among repeated injections but not among doses. Overall, pharmacokinetic parameters in goats are similar to those reported in cattle and swine, and tulathromycin may prove a useful drug for treating respiratory disease in goats.

  14. Determination of Clofarabine in rat plasma and the pharmacokinetic research%氯法拉滨大鼠血药浓度检测及药动学研究

    Institute of Scientific and Technical Information of China (English)

    马张庆; 洪宗元; 栾家杰

    2011-01-01

    AIM: To establish an HPLC method for the determination of Clofarabine concentration in the plasma of rats and calculate the pharmacokinetic parameters. METHODS.- All the samples were separated on a Agilent ODS Hypersil C18 analytical column (150 mm X 4. 6 mm,5 μm) by a mobile phase of acetonitrile-wa-ter(16 ! 84). The analytical column temperature was 30 'C , the ultraviolet detection wavelength was at 263 nm, and the flow rate was 1.2 mL/min. The dosage of 30 mg/kg was used for the intravenous injection of Clofarabine before we took blood from each rat at 0. 17, 0. 33, 0. 5, 0. 75, 1.0, 1. 5, 2.0, 4.0 and 8. 0 h post administration. The plasma concentration of Clofarabine was measured by HPLC. RESULTS: The chromatographic peak of Clofarabine was separated completely with the impurities in rat plasma. Good linearity was found over the range of 0. 05- 20.0 μg/mL for Clofarabine determination (the linear equation was y = 21. 758.r-0. 9155, r = 0. 999910). The recovery of methodology was 95%-105%, the inter- and intra-day precisions were both less than 10%. The concentration time curve of Clofarabine in rat could be fitted to two compartment model, and the major pharmacokinetic parameters were as follows: A= 14. 20 ± 2.45,B= 1.81 ± 0.51, CL =(2.91 + 0.47) L ? H-1 ? Kg-1, AUC(o-t) = ( 10. 22 ± 1. 88 ) mg? L-1 ? H,t1/2β = (2.03±0. 16) h. CONCLUSION- This method is selective and sensitive for Clofarabine determination, and can also be used in pharmacokinetic research. The drug shows us a two-compartment model in rat plasma, and it's half-life in plasma of rats was 2 h.%目的:建立氯法拉滨血药浓度HPLC检测法,研究其在大鼠体内的血浆药动学.方法:色谱条件为Agilent ODS Hypersil C18分析柱(150 mm×4.6 mm,5μm),柱温30℃,紫外检测波长263 nm,流动相为乙腈-水(16:84),乙酸调pH =4.0,流速1.2 mL/min;氯法拉滨30 mg/kg静脉注射,于给药后0.17、0.33、0.5、0.75、1.0、1.5、2.0、4.0、8.0h取血,测血药浓度.结

  15. GeV electron acceleration by a Gaussian field laser with effect of beam width parameter in magnetized plasma

    Science.gov (United States)

    Ghotra, Harjit Singh; Kant, Niti

    2017-01-01

    Electron acceleration due to a circularly polarized (CP) Gaussian laser field has been investigated theoretically in magnetized plasma. A Gaussian laser beam possesses trapping forces on electrons during its propagation through plasma. A single particle simulation indicates a resonant enhancement of electron acceleration with a Gaussian laser beam. The plasma is magnetized with an axial magnetic field in same direction as that of laser beam propagation. The dependence of laser beam width parameter on electron energy gain with propagation distance has been presented graphically for different values of laser intensity. Electron energy gain is relatively high where the laser beam parameter is at its minimum value. Enhanced energy gain of the order of GeV is reported with magnetic field under 20 MG in plasma. It is also seen that the axial magnetic field maintains the electron acceleration for large propagation distance even with an increasing beam width parameter.

  16. Relationship between Lipids Levels of Serum and Seminal Plasma and Semen Parameters in 631 Chinese Subfertile Men.

    Directory of Open Access Journals (Sweden)

    Jin-Chun Lu

    Full Text Available This prospective study was designed to investigate the relationship between lipids levels in both serum and seminal plasma and semen parameters.631 subfertile men were enrolled. Their obesity-associated markers were measured, and semen parameters were analyzed. Also, seminal plasma and serum TC, TG, HDL and LDL and serum FFA, FSH, LH, total testosterone (TT, estradiol (E2 and SHBG levels were detected.Seminal plasma and serum TG, TC and LDL levels were positively related to age. Serum TC, TG and LDL were positively related to obesity-associated markers (P < 0.001, while only seminal plasma TG was positively related to them (P < 0.05. For lipids levels in serum and seminal plasma, only TG level had slightly positive correlation between them (r = 0.081, P = 0.042. There was no significant correlation between serum lipids levels and semen parameters. However, seminal plasma TG, TC, LDL and HDL levels were negatively related to one or several semen parameters, including semen volume (SV, sperm concentration (SC, total sperm count (TSC, sperm motility, progressive motility (PR and total normal-progressively motile sperm counts (TNPMS. Moreover, seminal plasma TG, TC, LDL and HDL levels in patients with oligospermatism, asthenospermia and teratozoospermia were higher than those with normal sperm concentration, motility or morphology. After adjusting age and serum LH, FSH, TT, E2 and SHBG levels, linear regression analysis showed that SV was still significantly correlated with seminal plasma LDL (P = 0.012, both of SC and TSC with seminal plasma HDL (P = 0.028 and 0.002, and both of PR and sperm motility with seminal plasma TC (P = 0.012 and 0.051.The abnormal metabolism of lipids in male reproductive system may contribute to male factor infertility.

  17. Pharmacokinetics of Tyrosol Metabolites in Rats

    OpenAIRE

    Da-Hye Lee; Yang-Ji Kim; Min Jung Kim; Jiyun Ahn; Tae-Youl Ha; Sang Hee Lee; Young Jin Jang; Chang Hwa Jung

    2016-01-01

    Tyrosol is considered a potential antioxidant; however, little is known regarding the pharmacokinetics of its metabolites. To study the pharmacokinetics of tyrosol-derived metabolites after oral administration of a single dose of tyrosol, we attempted to identify tyrosol metabolites in rat plasma by using ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Two tyrosol metabolites (M1 and M2) were detected in the plasma. M1 was identified as...

  18. Long-Term Effect of Rifampicin-Based Anti-TB Regimen Coadministration on the Pharmacokinetic Parameters of Efavirenz and 8-Hydroxy-Efavirenz in Ethiopian Patients.

    Science.gov (United States)

    Habtewold, Abiy; Aklillu, Eleni; Makonnen, Eyasu; Amogne, Wondwossen; Yimer, Getnet; Aderaye, Getachew; Bertilsson, Leif; Owen, Joel S; Burhenne, Jürgen

    2016-12-01

    We compared the pharmacokinetic (PK) exposure parameters of efavirenz (EFV) and its major inactive metabolite, 8-hydroxy-efavirenz (8-OH-EFV), in an open-label, single-sequence, and parallel design of HIV-infected and tuberculosis (TB)-HIV-coinfected Ethiopian patients in the HIV-TB Pharmagene study with 20 and 33 patients, respectively. Both treatment groups underwent PK sampling following oral 600 mg EFV in week 16 of initiating EFV-based combination antiretroviral therapy. The TB-HIV-coinfected group repeated the PK sampling 8 weeks after stopping rifampin (RIF)-based anti-TB treatment. Between-treatment group analysis indicated no significant effect of RIF-based anti-TB cotreatment on PK exposure parameters of EFV, nor was there a significant effect after controlling for sex or CYP2B6 genotype. However, RIF-based therapy in TB-HIV-coinfected patients had significantly increased 8-OH-EFV PK exposure measures and metabolic ratio relative to HIV-only patients, AUC0-24 greater by 79%. The effect was more prominent in women and CYP2B6*6 carriers in within-sex and CYP2B6 genotype comparisons. Within-subject comparisons for AUC0-24 and Cmax when "on" and "off" RIF-based anti-TB cotreatment showed geometric mean ratios (90% confidence intervals) of 100.5% (98.7%-102.3%) and 100.2% (98.1%-102.4%), respectively, for EFV and 98.6% (95.5%-101.7%-) and 97.6% (92.2%-103.0%), respectively, for 8-OH-EFV. We report no significant influence of RIF-based anti-TB cotherapy on the EFV PK exposure measures. The study also calls for caution related to higher exposure to 8-OH-EFV during simultaneous coadministration of EFV and RIF-based anti-TB regimens, which may be associated with neurotoxicity, particularly in female patients and CYP2B6*6 carriers. © 2016, The American College of Clinical Pharmacology.

  19. HPLC法测定胃癌患者卡培他滨血药浓度及其药动学研究%Determination of Plasma Concentration of Capecitabine in Patients with Gastric Cancer and Its Pharmacokinetics Study

    Institute of Scientific and Technical Information of China (English)

    余俊先; 孟化; 王康里; 史丽敏; 王汝龙

    2013-01-01

    目的:建立卡培他滨的血药浓度测定方法并对其在胃癌患者体内的药动学进行初步探讨.方法:入组4例胃癌患者,其血浆以替硝唑为内标,以叔丁基甲醚进行提取后进样测定,色谱柱为Eclipse C18,流动相为乙腈-水(26∶74),检测波长为310nm,流速为1.0 ml/min.血药浓度数据用DAS药动学计算机程序处理.结果:卡培他滨与内标替硝唑分离良好,保留时间分别为8.15、3.15 min,卡培他滨血药浓度在0.05~8.00 μg/ml范围内线性关系良好;日内、日间RSD均<7%,提取回收率在77.04%~87.53%范围内;卡培他滨的药动学参数Cmax、tmax、t1/2β、AUC0-6h分别为(5.42±2.90)μg/ml、(1.0±0.71)h、(1.01±0.50)h和(9.54±5.32)mg·h/L.结论:胃癌患者口服卡培他滨后吸收迅速,消除半衰期短,个体之间生物利用度差异显著.%OBJECTIVE: To establish a method for the determination of plasma concentration of capecitabine, and to explore its pharmacokinetics in gastric carcinoma subject. METHODS: 4 gastric carcinoma subjects were enrolled. Using tinidazole as internal standard, plasma was extracted with tert-butyl methyl ether. The determination was performed on Eclipse C18 column with mobile phase consisted of acetonitrile-water (26:74) at the flow rate of 1.0 ml/min. The detection wavelength was set at 310 nm. The plasma concentration of capecitabine was processed by DAS computer program. RESULTS: Capecitabine was well-separated from tinidazole, and the retention time of them were about 8.15 min and 3.15 min, respectively. Linear range of capecitabine was 0.05-8.00 μg/ml. RSD of intra-day and inter-day were lower than 7% and extraction recoveries were 77.04%-87.53% ; pharmacoki-netic parameters of capecitabine were as follows: Cmax was (5.42 ± 2.90)μg/ml; tmax was (1.0 ± 0.71)h; tmax was (1.01 ± 0.50)h; AUC0-6h was (9.54 ± 5.32)mg·h/L, respectively. CONCLUSION: Capecitabine in gastric carcinoma subjects is quickly absorbed and

  20. Nuclear magnetic resonance-based metabonomics reveals strong sex effect on plasma metabolism in 17-year-old Scandinavians and correlation to retrospective infant plasma parameters.

    Science.gov (United States)

    Bertram, Hanne Christine; Duus, Jens Ø; Petersen, Bent O; Hoppe, Camilla; Larnkjaer, Anni; Schack-Nielsen, Lene; Mølgaard, Christian; Michaelsen, Kim F

    2009-07-01

    Nuclear magnetic resonance (NMR)-based metabonomics was carried out on plasma samples from a total of seventy-five 17-year-old Danes to investigate the impact of key parameters such as sex, height, weight, and body mass index on the plasma metabolite profile in a normal, healthy population. Principal component analysis identified sex to have a large impact on the NMR plasma metabolome, whereas no apparent effects of height, weight, and body mass index were found. Partial least square regression discriminant analysis and quantification of relative metabolite concentrations by integration of NMR signals revealed that the sex effect included differences in plasma lipoproteins (mainly high-density lipoprotein), glucose, choline, and amino acid content. Accordingly, the present study suggests a higher lipid synthesis in young women than young men and a higher protein turnover in young men compared with women. Data on plasma content of triglyceride, lipoprotein fractions, and cholesterol at an age of 9 months were available for selected individuals (n = 40); and partial least square regressions revealed correlations between these infant parameters and the NMR plasma metabolome at an age of 17 years. In conclusion, the present study demonstrates the feasibility of NMR-based metabonomics for obtaining a deeper insight into interindividual differences in metabolism and for exploring relationships between parameters measured early in life and metabolic status at a later stage.

  1. Relationships between organohalogen contaminants and blood plasma clinical–chemical parameters in chicks of three raptor species from Northern Norway

    DEFF Research Database (Denmark)

    Sonne, Christian; Bustnes, Jan Ove; Herzke, Dorte

    2010-01-01

    Organohalogen contaminants (OHCs) may affect various physiological parameters in birds including blood chemistry. We therefore examined blood plasma clinical-chemical parameters and OHCs in golden eagle, white-tailed eagle and goshawk chicks from Northern Norway. Correlation analyses on pooled da...

  2. Relation of Plasma Uric Acid Levels and the Lipid Parameters in Han and Uygur Ethnicity

    Institute of Scientific and Technical Information of China (English)

    Sun Yuping; Yao Hua; Yao Wenhai; Li Qing; You Lan; Wang Qiuyun; Jiang Yan

    2006-01-01

    Objectives Hyperuricemia is a common finding in hypertension and hyperlipidemia,they are all correlated to cardiovascular diseases. The aim of this study was to find the relationship of uric acid and plasma lipid parameters of Han and Uygur ethnicity in Xinjiang. Methods This cross-sectional health examination survey was based on a population random sample from the Urumchi, It included 1166 subjects aged from 20 to 70 years. Serum biochemical testing by Automatic Analyzer (HITACHI 7600-010).Results The uric acid in Han was higher than in Uygur(P< 0.05), men were higher than women in two ethnicities; For lipid parameters men were higher than women, in TG and HDL women were higher than in men in two ethnicity (P < 0.05). Serum uric acid was strongly related to serum triglycerides in Han as well as Uygur ethnicity ( P < 0.001); Compared with the normal group, UA, TG, CHOL, VLDL had ascending trend and HDL had descending trend (P <0.05 ) among groups in Han and Uygur ethnicity,especially Hyperuricemia-hypertriglyceridemia group,uric acid and most some lipid parameters was higher than Hyperuricemia and hypertriglyceridemia group,The prevalence of different groups in Han and Urgur was significantly different (P < 0.05). Conclusions This study shows that the UA and some lipid parameters are different in Han and Uygur ethnicity and show sexual difference; serum uric acid is markedly related to serum triglycerides; Hyperuricemia and hypertriglyceridemia show cooperated effect in uric acid and most lipid parameters. Considering the growing incidence of the potential link between hyperuricemia/hypertriglyceridemia and cardiovascular diseases, more emphasis should be put on the evolving prevalence of hyperuricemia and hypertriglyceridemia in Xinjiang.

  3. Liquid chromatography–tandem mass spectrometry method for the estimation of adefovir in human plasma: Application to a pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Dipanjan Goswami

    2015-06-01

    Full Text Available An analytical method based on solid phase extraction was developed and validated for analysis of adefovir in human plasma. Adefovir-d4 was used as an internal standard and Synergi MAX RP80A (150 mm×4.6 mm, 4 µm column provided the desired chromatographic separation of compounds followed by detection with mass spectrometry. The method used simple isocratic chromatographic condition and mass spectrometric detection in the positive ionization mode. The calibration curves were linear over the range of 0.50–42.47 ng/mL with the lower limit of quantitation validated at 0.50 ng/mL. Matrix effect was assessed by post-column infusion experiment to monitor phospholipids and post-extraction addition experiment was performed. The degree of matrix effect for adefovir was determined as 7.5% and ion-enhancement in five different lots of human plasma was 7.1% and had no impact on study samples analysis with 4.5 min run time. The intra- and inter-day precision values were within 7.7% and 7.8%, respectively, for adefovir at the lower limit of quantification level. Validated bioanalytical method was successfully applied to clinical sample analysis.

  4. Pharmacokinetics of Vancomycin in Elderly Patients Aged over 80 Years.

    Science.gov (United States)

    Bourguignon, Laurent; Cazaubon, Yoann; Debeurme, Guillaume; Loue, Constance; Ducher, Michel; Goutelle, Sylvain

    2016-08-01

    Since the 1950s, vancomycin has remained a reference treatment for severe infections caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus Vancomycin is a nephrotoxic and ototoxic drug mainly eliminated through the kidneys. It has a large interindividual pharmacokinetic variability, which justifies monitoring its plasma concentrations in patients. This is especially important in patients aged over 80 years, who frequently have renal impairment. However, the pharmacokinetics of vancomycin in this population is very poorly described in the literature. The objective of this work was to propose a model able to predict the pharmacokinetics of vancomycin in very elderly people. First, a population pharmacokinetic model was carried out using the algorithm NPAG (nonparametric adaptive grid) on a database of 70 hospitalized patients aged over 80 years and treated with vancomycin. An external validation then was performed on 41 patients, and the predictive capabilities of the model were assessed. The model had two compartments and six parameters. Body weight and creatinine clearance significantly influenced vancomycin volume of distribution and body clearance, respectively. The means (± standard deviations) of vancomycin volume of distribution and clearance were 36.3 ± 15.2 liter and 2.0 ± 0.9 liter/h, respectively. In the validation group, the bias and precision were -0.75 mg/liter and 8.76 mg/liter for population predictions and -0.39 mg/liter and 2.68 mg/liter for individual predictions. In conclusion, a pharmacokinetic model of vancomycin in a very elderly population has been created and validated for predicting plasma concentrations of vancomycin.

  5. LC-UV Determination of Baicalin in Rabbit Plasma and Tissues for Application in Pharmacokinetics and Tissue Distribution Studies of Baicalin after Intravenous Administration of Liposomal and Injectable Formulations.

    Science.gov (United States)

    Wei, Yumeng; Pi, Chao; Yang, Gang; Xiong, Xiaoming; Lan, Yongshu; Yang, Hongru; Zhou, Yang; Ye, Yun; Zou, Yonggen; Zheng, Wenwu; Zhao, Ling

    2016-04-19

    A simple and sensitive LC-UV method to investigate the pharmacokinetics and biodistribution pattern of baicalin in rabbits was established and validated. Baicalin and the internal standard, rutin, were extracted from biosamples using acetonitrile as protein precipitation after pretreated with ammonium acetate buffer (pH 3.5; 1 M) to obtain a pure chromatographic peak and high extraction recovery. Chromatographic separation was achieved on a reverse-phase C18 column with a gradient elution at flow rate of 1.0 mL/min. UV absorption was set at 278 nm. Chromatographic response was linear over the ranges of 0.05-10.00 μg/mL in plasma and 0.05-300.00 μg/g in tissues with the limits of quantification of 50.0 ng/mL in plasma and tissues, and the limit of detection of baicalin in bio-samples of 15 ng/mL. The RSD of intra-and inter-day for the biosamples were from 4.19% to 10.84% and from 4.37% to 10.93%, respectively. The accuracy of plasma and tissue samples ranged from 81.6% to 95.2% and 80.8% to 98.4%, respectively. The extraction recoveries ranged from 81.5% to 88.3% for plasma, from 73.1% to 93.2% for tissues, respectively. Baicalin was stable in rabbit biosamples. The validated method was successfully applied to the study of the pharmacokinetics and tissue distribution of baicalin after intravenous administration of liposomal and injectable formulations to rabbits. Compared to baicalin injection, the pharmacokinetics and biodistribution behavior of baicalin was altered significantly in rabbits treated with its liposomes and drug concentration in the lungs was greatly increased.

  6. Relationship between Lipids Levels of Serum and Seminal Plasma and Semen Parameters in 631 Chinese Subfertile Men

    Science.gov (United States)

    Yao, Qi; Fan, Kai; Wang, Guo-Hong; Feng, Rui-Xiang; Liang, Yuan-Jiao; Chen, Li; Ge, Yi-Feng; Yao, Bing

    2016-01-01

    Objective This prospective study was designed to investigate the relationship between lipids levels in both serum and seminal plasma and semen parameters. Methods 631 subfertile men were enrolled. Their obesity-associated markers were measured, and semen parameters were analyzed. Also, seminal plasma and serum TC, TG, HDL and LDL and serum FFA, FSH, LH, total testosterone (TT), estradiol (E2) and SHBG levels were detected. Results Seminal plasma and serum TG, TC and LDL levels were positively related to age. Serum TC, TG and LDL were positively related to obesity-associated markers (P lipids levels in serum and seminal plasma, only TG level had slightly positive correlation between them (r = 0.081, P = 0.042). There was no significant correlation between serum lipids levels and semen parameters. However, seminal plasma TG, TC, LDL and HDL levels were negatively related to one or several semen parameters, including semen volume (SV), sperm concentration (SC), total sperm count (TSC), sperm motility, progressive motility (PR) and total normal-progressively motile sperm counts (TNPMS). Moreover, seminal plasma TG, TC, LDL and HDL levels in patients with oligospermatism, asthenospermia and teratozoospermia were higher than those with normal sperm concentration, motility or morphology. After adjusting age and serum LH, FSH, TT, E2 and SHBG levels, linear regression analysis showed that SV was still significantly correlated with seminal plasma LDL (P = 0.012), both of SC and TSC with seminal plasma HDL (P = 0.028 and 0.002), and both of PR and sperm motility with seminal plasma TC (P = 0.012 and 0.051). Conclusion The abnormal metabolism of lipids in male reproductive system may contribute to male factor infertility. PMID:26726884

  7. Lumping in pharmacokinetics.

    Science.gov (United States)

    Brochot, Céline; Tóth, János; Bois, Frédéric Y

    2005-12-01

    Pharmacokinetic (PK) models simplify biological complexity by dividing the body into interconnected compartments. The time course of the chemical's amount (or concentration) in each compartment is then expressed as a system of ordinary differential equations. The complexity of the resulting system of equations can rapidly increase if a precise description of the organism is needed. However, difficulties arise when the PK model contains more variables and parameters than comfortable for mathematical and computational treatment. To overcome such difficulties, mathematical lumping methods are new and powerful tools. Such methods aim at reducing a differential system by aggregating several variables into one. Typically, the lumped model is still a differential equation system, whose variables are interpretable in terms of variables of the original system. In practice, the reduced model is usually required to satisfy some constraints. For example, it may be necessary to keep state variables of interest for prediction unlumped. To accommodate such constraints, constrained lumping methods have are also available. After presenting the theory, we study, here, through practical examples, the potential of such methods in toxico/pharmacokinetics. As a tutorial, we first simplify a 2-compartment pharmacokinetic model by symbolic lumping. We then explore the reduction of a 6-compartment physiologically based pharmacokinetic model for 1,3-butadiene with numerical constrained lumping. The lumping methods presented here can be easily automated, and are applicable to first-order ordinary differential equation systems.

  8. Feed gas humidity: a vital parameter affecting a cold atmospheric-pressure plasma jet and plasma-treated human skin cells

    Science.gov (United States)

    Winter, J.; Wende, K.; Masur, K.; Iseni, S.; Dünnbier, M.; Hammer, M. U.; Tresp, H.; Weltmann, K.-D.; Reuter, S.

    2013-07-01

    In this study, the effect of feed gas humidity on the reactive component generation of an atmospheric-pressure argon plasma jet and its effect on human skin cells are investigated. Feed gas humidity is identified as one key parameter that strongly influences stability and reproducibility of plasma medical studies. The plasma jet is investigated by absorption spectroscopy in the ultraviolet and infrared spectral region for its ozone production depending on the humidity concentration in the feed gas. By optical emission spectroscopy the dependence of present excited plasma species such as hydroxyl radicals, molecular nitrogen, argon and atomic oxygen on the feed gas humidity is investigated. As an interface layer between the plasma jet effluent and the biological cell, a buffer solution is treated and the hydrogen peroxide (H2O2) production is studied with two independent colorimetric assays as a function of humidity admixture to the feed gas. Ultimately, the effect of varying feed gas humidity on the cell viability of indirect plasma treated adherent HaCAT cells is investigated. The highest viability is found for the driest feed gas condition. Furthermore, this work shows answers for the relevance of unwanted—or intended—feed gas humidity in plasma medical experiments and their comparatively large relevance with respect to ambient humidity. The findings will lead to more reproducible experiments in the field of plasma medicine.

  9. Plasma polymers deposited in atmospheric pressure dielectric barrier discharges: Influence of process parameters on film properties

    Energy Technology Data Exchange (ETDEWEB)

    Fricke, Katja, E-mail: k.fricke@inp-greifswald.de [Leibniz Institute for Plasma Science and Technology e.V. (INP Greifswald), Felix-Hausdorff-Str. 2, 17489 Greifswald (Germany); Girard-Lauriault, Pierre-Luc [Plasma Processing Laboratory, Department of Chemical Engineering, McGill University, 3610 rue University, Montreal, QC H3A 0C5 (Canada); Weltmann, Klaus-Dieter [Leibniz Institute for Plasma Science and Technology e.V. (INP Greifswald), Felix-Hausdorff-Str. 2, 17489 Greifswald (Germany); Wertheimer, Michael R. [Department of Engineering Physics, École Polytechnique de Montréal, Box 6079, Station Centre-Ville, Montreal, QC H3C 3A7 (Canada)

    2016-03-31

    We present results on the deposition of plasma polymer (PP) films in a dielectric barrier discharge system fed with mixtures of argon or nitrogen carrier gas plus different hydrocarbon precursors, where the latter possess different carbon-to-hydrogen ratios: CH{sub 4} < C{sub 2}H{sub 6} < C{sub 2}H{sub 4} = C{sub 3}H{sub 6} < C{sub 2}H{sub 2}. The influence of precursor gas mixture and flow rate, excitation frequency, and absorbed power on PP film compositions and properties has been investigated. The discharge was characterized by electrical measurements, while the chemical compositions and structures of coatings were analysed by X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, total combustion, and elastic recoil detection analyses, the latter two for determining carbon-to-hydrogen ratios. Scanning electron microscopy was used to study the coatings' morphology, and profilometry for evaluating deposition rates. - Highlights: • Atmospheric pressure DBD is used to deposit organic hydrocarbon films. • High deposition rates can be achieved by varying the power and/or gas mixture ratio. • Process parameters affect the films' surface chemical composition and morphology. • Deposited films are not soluble in aqueous environment. • No delamination of coatings produced from argon plasma.

  10. Development of two step liquid-liquid extraction tandem UHPLC-MS/MS method for the simultaneous determination of Ginkgo flavonoids, terpene lactones and nimodipine in rat plasma: Application to the pharmacokinetic study of the combination of Ginkgo biloba dispersible tablets and Nimodipine tablets.

    Science.gov (United States)

    Xiao, Jie; Wang, Tianyang; Li, Pei; Liu, Ran; Li, Qing; Bi, Kaishun

    2016-08-15

    A sensitive, reliable and accurate UHPLC-MS/MS method has been firstly established and validated for the simultaneous quantification of ginkgo flavonoids, terpene lactones and nimodipine in rat plasma after oral administration of Ginkgo biloba dispersible tablets, Nimodipine tablets and the combination of the both, respectively. The plasma samples were extracted by two step liquid-liquid extraction, nimodipine was extracted by hexane-ether (3:1, v/v) at the first step, after that ginkgo flavonoids and terpene lactones were extracted by ethyl acetate. Then the analytes were successfully separated by running gradient elution with the mobile phase consisting of 0.1% formic acid in water and methanol at a flow rate of 0.6mL/min. The detection of the analytes was performed on a UHPLC-MS/MS system with turbo ion spray source in the negative ion and multiple reaction monitoring (MRM) mode. The calibration curves for the determination of all the analytes showed good linearity (R(2)>0.99), and the lower limits of quantification were 0.50-4.00ng/mL. Intra-day and inter-day precisions were in the range of 3.6%-9.2% and 3.2%-13.1% for all the analytes. The mean extraction recoveries of the analytes were within 69.82%-103.5% and the matrix were within 82.8%-110.0%. The validated method had been successfully applied to compare the pharmacokinetic parameters of ginkgo flavonoids, terpene lactones and nimodipine in rat plasma after oral administration of Ginkgo biloba dispersible tablets, Nimodipine tablets with the combination of the both. There were no statistically significant differences on the pharmacokinetic behaviors of all the analytes between the combined and single administration groups. Results showed that the combination of the two agents may avoid dosage adjustments in clinic and the combination is more convenient as well as efficient on different pathogenesis of cerebral ischemia.

  11. Pharmacokinetic modeling of ascorbate diffusion through normal and tumor tissue.

    Science.gov (United States)

    Kuiper, Caroline; Vissers, Margreet C M; Hicks, Kevin O

    2014-12-01

    Ascorbate is delivered to cells via the vasculature, but its ability to penetrate into tissues remote from blood vessels is unknown. This is particularly relevant to solid tumors, which often contain regions with dysfunctional vasculature, with impaired oxygen and nutrient delivery, resulting in upregulation of the hypoxic response and also the likely depletion of essential plasma-derived biomolecules, such as ascorbate. In this study, we have utilized a well-established multicell-layered, three-dimensional pharmacokinetic model to measure ascorbate diffusion and transport parameters through dense tissue in vitro. Ascorbate was found to penetrate the tissue at a slightly lower rate than mannitol and to travel via the paracellular route. Uptake parameters into the cells were also determined. These data were fitted to the diffusion model, and simulations of ascorbate pharmacokinetics in normal tissue and in hypoxic tumor tissue were performed with varying input concentrations, ranging from normal dietary plasma levels (10-100 μM) to pharmacological levels (>1 mM) as seen with intravenous infusion. The data and simulations demonstrate heterogeneous distribution of ascorbate in tumor tissue at physiological blood levels and provide insight into the range of plasma ascorbate concentrations and exposure times needed to saturate all regions of a tumor. The predictions suggest that supraphysiological plasma ascorbate concentrations (>100 μM) are required to achieve effective delivery of ascorbate to poorly vascularized tumor tissue.

  12. HPLC determination of pirfenidone in rat plasma and its pharmacokinetics%HPLC法检测大鼠血浆中吡非尼酮的浓度及其药动学研究

    Institute of Scientific and Technical Information of China (English)

    肖敏; 李军伟; 孙未; 罗顺斌; 胡国新

    2012-01-01

    目的:建立大鼠血浆吡非尼酮检测的高效液相色谱方法,研究吡非尼酮的药代动力学.方法:血浆经乙酸乙酯,采用ZORBAX SB - C18色谱柱;流动相为乙腈-水-0.1% TFA(三氟乙酸),流速为1.0mL·min-1;检测波长为318(0 ~8 min)、246nm(8~10 min).6只雄性大鼠单剂量灌胃给予15 mg·kg-1吡非尼酮,分别在给药后多点尾静脉采血;用该方法检测血浆中吡非尼酮的浓度.用DAS(数据采集系统)计算药代动力学参数.结果:吡非尼酮浓度在0.025~4.00 mg·L-1范围内线性关系良好(r =0.9999);定量下限为0.025 mg· L-1;低、中、高3个浓度的相对回收率分别为(100.40±4.66)%、(102.17±4.02)%和(101.12±2.89)%;日内RSD分别为4.6%,3.9%,2.9%,日间RSD分别为5.5%,4.8%,3.7%.大鼠吡非尼酮灌胃后,血浆吡非尼酮在0.39 h达到1.69 mg·L-1的峰值浓度,血浆半衰期为2.21 h.吡非尼酮在大鼠体内符合一级吸收的二室模型.结论:本方法准确可靠、简便快速,适用于大鼠血浆吡非尼酮浓度的测定及其药代动力学研究.%Objective:To develop an HPLC method for the determination of pirfenidone in rat plasma and study its pharmacokinetics. Methods: The plasma was extracted by ethyl acetate. The analytical column was packed with ZORBAX SB -C18. The mobile phase were acetonitrile -water -0. 1% trifluoroacetic acid at the flow rate of 1. 0 mL · min-1. The UV detection wavelength was 318 nm (0-8 min) ,246 nm (8 - 10 min). Six Wistar male rats were given a single 20 mg · kg-1 oral dose of pirfenidone. Blood samples were collected from the tail vein at different time points after oral administration. The concentration of pirfenidone in plasma were detected by this HPLC methods. The pharmacokinetic parameters were analyzed by DAS program. Results: Excellent liner relationship was obtained from the range of 0. 025 mg · L-1 to 4. 00 mg · L-1 ( r = 0. 999 9 ) , the limit determination of pirfenidone was 0

  13. Population pharmacokinetics of phenobarbital in infants with neonatal encephalopathy treated with therapeutic hypothermia.

    Science.gov (United States)

    Shellhaas, Renée A; Ng, Chee M; Dillon, Christina H; Barks, John D E; Bhatt-Mehta, Varsha

    2013-02-01

    Phenobarbital is the first-line treatment for neonatal seizures. Many neonates with hypoxic ischemic encephalopathy are treated with therapeutic hypothermia, and about 40% have clinical seizures. Little is known about the pharmacokinetics of phenobarbital in infants with hypoxic ischemic encephalopathy who undergo therapeutic hypothermia. The objective of this study was to determine the effect of therapeutic hypothermia on phenobarbital pharmacokinetics, taking into account maturational changes. Level 3 neonatal ICU. Infants with hypoxic ischemic encephalopathy and suspected seizures, all treated with phenobarbital. Some of these infants also received treatment with therapeutic hypothermia. None. A retrospective cohort study of 39 infants with hypoxic ischemic encephalopathy treated with phenobarbital (20 were treated with therapeutic hypothermia and 19 were not). Data on phenobarbital plasma concentrations were collected in 39 subjects with hypoxic ischemic encephalopathy with or without therapeutic hypothermia. Using nonlinear mixed-effects modeling, population pharmacokinetics of phenobarbital were developed with a total of 164 plasma concentrations. A one-compartment model best described the pharmacokinetics. The clearance of phenobarbital was linearly related to body weight and matured with increasing age with a maturation half-life of 22.1 days. Therapeutic hypothermia did not influence the pharmacokinetic parameters of phenobarbital. Therapeutic hypothermia does not influence the clearance of phenobarbital after accounting for weight and age. Standard phenobarbital dosing is appropriate for the initial treatment of seizures in neonates with hypoxic ischemic encephalopathy treated with therapeutic hypothermia.

  14. 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.

  15. The pharmacokinetics of intravenous fenoldopam in healthy, awake cats.

    Science.gov (United States)

    O'Neill, K E; Labato, M A; Court, M H

    2016-04-01

    Fenoldopam is a selective dopamine-1 receptor agonist that improves diuresis by increasing renal blood flow and perfusion and causing peripheral vasodilation. Fenoldopam has been shown to induce diuresis and be well-tolerated in healthy cats. It is used clinically in cats with oliguric kidney injury at doses extrapolated from human medicine and canine studies. The pharmacokinetics in healthy beagle dogs has been reported; however, pharmacokinetic data in cats are lacking. The goal of this study was to determine pharmacokinetic data for healthy, awake cats receiving an infusion of fenoldopam. Six healthy, awake, client-owned cats aged 2-6 years old received a 120-min constant rate infusion of fenoldopam at 0.8 μg/kg/min followed by a 20-min washout period. Ascorbate stabilized plasma samples were collected during and after the infusion for the measurement of fenoldopam concentration by HPLC with mass spectrometry detection. This study showed that the geometric mean of the volume of distribution, clearance, and half-life (198 mL/kg, 46 mL/kg/min, and 3.0 mins) is similar to pharmacokinetic parameters for humans. No adverse events were noted. Fenoldopam at a constant rate infusion of 0.8 μg/kg per min was well tolerated in healthy cats. Based on the results, further evaluation of fenoldopam in cats with kidney disease is recommended. © 2016 John Wiley & Sons Ltd.

  16. A Systematic Analysis of the Sensitivity of Plasma Pharmacokinetics to Detect Differences in the Pulmonary Performance of Inhaled Fluticasone Propionate Products Using a Model-Based Simulation Approach.

    Science.gov (United States)

    Weber, Benjamin; Hochhaus, Guenther

    2015-07-01

    The role of plasma pharmacokinetics (PK) for assessing bioequivalence at the target site, the lung, for orally inhaled drugs remains unclear. A validated semi-mechanistic model, considering the presence of mucociliary clearance in central lung regions, was expanded for quantifying the sensitivity of PK studies in detecting differences in the pulmonary performance (total lung deposition, central-to-peripheral lung deposition ratio, and pulmonary dissolution characteristics) between test (T) and reference (R) inhaled fluticasone propionate (FP) products. PK bioequivalence trials for inhaled FP were simulated based on this PK model for a varying number of subjects and T products. The statistical power to conclude bioequivalence when T and R products are identical was demonstrated to be 90% for approximately 50 subjects. Furthermore, the simulations demonstrated that PK metrics (area under the concentration time curve (AUC) and C max) are capable of detecting differences between T and R formulations of inhaled FP products when the products differ by more than 20%, 30%, and 25% for total lung deposition, central-to-peripheral lung deposition ratio, and pulmonary dissolution characteristics, respectively. These results were derived using a rather conservative risk assessment approach with an error rate of <10%. The simulations thus indicated that PK studies might be a viable alternative to clinical studies comparing pulmonary efficacy biomarkers for slowly dissolving inhaled drugs. PK trials for pulmonary efficacy equivalence testing should be complemented by in vitro studies to avoid false positive bioequivalence assessments that are theoretically possible for some specific scenarios. Moreover, a user-friendly web application for simulating such PK equivalence trials with inhaled FP is provided.

  17. Development and validation of a LC-MS/MS method for determination of pinoresinol diglucoside in rat plasma: Application to pharmacokinetic study.

    Science.gov (United States)

    Song, Yanqing; Yan, Huiyu; Sun, Zhihui; Teng, Shiyong; Sun, Lirui; Zhang, Sixi

    2015-11-01

    Pinoresinol diglucoside (PD), a typical marker compound in Ecommia ulmoides Oliv., is an important and natural antihypertensive drug. A selective, sensitive, and rapid liquid chromatography tandem mass spectrometric (LC-MS/MS) analytical method was developed for the determination of PD in rats. After simple protein precipitation with acetonitrile, chromatographic separation of PD was conducted using a reversed-phase ZORBAX SB C18 analytical column (4.6mm × 150 mm, 5 μm particles) with a mobile phase of 10mM ammonium acetate-methanol-acetic acid (50:50:0.15, v/v/v) and quantified by selected reaction monitoring mode under positive electrospray ionization condition. The chromatographic run time was 3.4 min for each sample, in which the retention times of PD and the internal standard were 2.87 and 2.65 min, respectively. The calibration curves were linear over the range of 1.00~3000 ng/mL and the lower limit of quantification was 1.00 ng/mL in rat plasma. The precision expressed by relative standard deviations were <8.9% for intra-batch precision and <2.0% for inter-batch precision, and the intra- and inter-batch accuracy by relative error was within the range of -3.9% ~7.3%, which met acceptable criteria. The LC-MS/MS method was successfully applied to investigate the pharmacokinetics and oral bioavailability of PD in rats, with the bioavailability being only 2.5%.

  18. A simple, rapid and sensitive RP-HPLC-UV method for the simultaneous determination of sorafenib & paclitaxel in plasma and pharmaceutical dosage forms: Application to pharmacokinetic study.

    Science.gov (United States)

    Khan, Ismail; Iqbal, Zafar; Khan, Abad; Hassan, Muhammad; Nasir, Fazle; Raza, Abida; Ahmad, Lateef; Khan, Amjad; Akhlaq Mughal, Muhammad

    2016-10-15

    A simple, economical, fast, and sensitive RP-HPLC-UV method has been developed for the simultaneous quantification of Sorafenib and paclitaxel in biological samples and formulations using piroxicam as an internal standard. The experimental conditions were optimized and method was validated according to the standard guidelines. The separation of both the analytes and internal standard was achieved on Discovery HS C18 column