Stereoselective analysis of fluvastatin in human plasma for pharmacokinetic studies

2001 ◽  
Vol 765 (1) ◽  
pp. 81-88 ◽  
Author(s):  
Vera Lucia Lanchote ◽  
Adriana Rocha ◽  
Flávio Ulliana Vieira de Albuquerque ◽  
Eduardo Barbosa Coelho ◽  
Pierina Sueli Bonato
Keyword(s):  
Human Plasma ◽  
Pharmacokinetic Studies

Liquid Chromatography-Tandem Mass Spectrometry Method for Ticagrelor and its Active Metabolite Determination in Human Plasma: Application to a Pharmacokinetic Study

2020 ◽  
Vol 16 (5) ◽  
pp. 602-608
Author(s):  
Niloufar Marsousi ◽  
Serge Rudaz ◽  
Jules A. Desmeules ◽  
Youssef Daali
Keyword(s):  
Clinical Trial ◽  
Formic Acid ◽  
Human Plasma ◽  
Active Metabolite ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Healthy Male ◽  
Coronary Syndrome ◽  
Healthy Male Volunteers ◽  
Male Volunteers

Background: Ticagrelor is a highly recommended new antiplatelet agent for the treatment of patients with acute coronary syndrome at moderate or high ischemic risk. There is a real need for rapid and accurate analytical methods for ticagrelor determination in biological fluids for pharmacokinetic studies. In this study, a sensitive and specific LC-MS method was developed and validated for quantification of ticagrelor and its Active Metabolite (AM) in human plasma over expected clinical concentrations. Methods: Samples were handled by Liquid-Liquid Extraction (LLE). A linear gradient was applied with a mobile phase composed of formic acid 0.1% and acetonitrile with 0.1% of formic acid using a C18 reversed-phase column. MS spectra were obtained by electrospray ionization in negative mode and optimized at 521.4→360.9 m/z, 477.2→361.2 m/z and 528.1→367.9 m/z transitions for ticagrelor, AM and ticagrelor-d7, respectively. Results: This method allowed rapid elution, in less than 4 minutes, and quantification of concentrations as low as 2 ng/mL for ticagrelor and 1 ng/mL for AM using only 100 μL of human plasma. LLE using hexane/ethyl acetate (50/50) was an optimal compromise in terms of extraction recovery and endogenous compounds interference. Trueness values of 87.8% and 89.5% and precisions of 84.1% and 93.8% were obtained for ticagrelor and AM, respectively. Finally, the usefulness of the method was assessed in a clinical trial where a single 180 mg ticagrelor was orally administered to healthy male volunteers. Pharmacokinetic parameters of ticagrelor and its active metabolite were successfully determined. Conclusion: A sensitive and specific quantification LC-MS-MS method was developed and validated for ticagrelor and its active metabolite determination in human plasma. The method was successfully applied to a clinical trial where a single ticagrelor 180 mg dose was orally administered to healthy male volunteers. The described method allows quantification of concentrations as low as 2 ng/mL of ticagrelor and 1 ng/mL of the metabolite using only 100 μL of plasma.

A Novel Simultaneous Estimation of Sofosbuvir and Velpatasvir in Human Plasma by Liquid Chromatography Tandem-Mass Spectrometry after Protein Precipitation Method

2019 ◽  
Vol 15 (7) ◽  
pp. 710-715
Author(s):  
S.T. Narenderan ◽  
Basuvan Babu ◽  
T. Gokul ◽  
Subramania Nainar Meyyanathan
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Human Plasma ◽  
Multiple Reaction Monitoring ◽  
Simultaneous Estimation ◽  
Pharmacokinetic Studies ◽  
Tandem Mass ◽  
Mass Spectrometric Method ◽  
Highly Sensitive ◽  
Tandem Mass Spectrometric

Objective: The aim of the present work is to achieve a novel highly sensitive chromatographic method for the simultaneous determination of hepatitis C agents, sofosbuvir and velpatasvir from human plasma using ritonavir as an internal standard. Methods: Chromatographic separation was achieved using Hypersil C18 column (50mm x 4.6mm, 3μm) with an isocratic elution mode using the mobile phase composition 10 mM ammonium formate buffer (pH 5.0): acetonitrile (20:80 v/v) pumped at a flow rate of 0.5 ml/min. The detection was carried out by tandem mass spectrometry using Multiple Reaction Monitoring (MRM) positive Electrospray Ionization (ESI) with proton adducts at m/z 530.10 > 243.10, 883.40 > 114.0 and 721.25 > 197.0. Results: The method validated as per USFDA guidelines with respect to linearity, accuracy, and precision was found to be acceptable over the concentration range of 0.2–2000 ng/ml and 5-2000 ng/ml for sofosbuvir and velpatasvir respectively and the method was found to be highly sensitive and selective. Conclusion: The developed tandem mass spectrometric method is robust and can be applied for the monitoring of plasma levels of the analyzed drug in preclinical and clinical pharmacokinetic studies.

AN EFFICIENT HPLC-UV METHOD FOR THE QUANTITATIVE DETERMINATION OF CEFADROXIL IN HUMAN PLASMA AND ITS APPLICATION IN PHARMACOKINETIC STUDIES

2012 ◽  
Vol 35 (13) ◽  
pp. 1871-1881 ◽  
Author(s):  
Eunice Kazue Kano ◽  
Cristina Helena dos Reis Serra ◽  
Eunice Emiko Mori Koono ◽  
Kazuo Fukuda ◽  
Valentina Porta
Keyword(s):  
Quantitative Determination ◽  
Human Plasma ◽  
Pharmacokinetic Studies

Simultaneous determination of novel ketolide antibiotic nafithromycin and its major metabolite in human plasma using liquid chromatography tandem mass spectrometry

Bioanalysis ◽  
2019 ◽  
Vol 11 (19) ◽  
pp. 1767-1776
Author(s):  
Kiran R Patil ◽  
Ravindra D Yeole ◽  
Marcel de Zwart ◽  
Peter Pruim
Keyword(s):  
Phase I ◽  
Human Plasma ◽  
Internal Standard ◽  
Pharmacokinetic Studies ◽  
Simultaneous Quantification ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Us Fda ◽  
Standard Protein

Aim: A sensitive method to quantify nafithromycin and its N-desmethyl metabolite in human plasma was necessary for Phase I pharmacokinetic studies. Methodology: A precise and accurate LC–MS/MS bioanalytical method has been developed and validated for the simultaneous quantification of nafithromycin (NFT, WCK 4873) and N-desmethyl metabolite (M1, WCK 4978) in human plasma. Clarithromycin was used as an internal standard. Protein precipitation technique was used as sample preparation approach. The calibration curve was linear (r ≥ 0.99) over the concentration range of 10–5000 ng/ml for NFT and M1. Method was validated as per US FDA guideline. Conclusion: The proposed method was successfully applied for determination of plasma levels of the NFT and M1 during Phase I clinical studies.

scholarly journals DEVELOPMENT AND VALIDATION OF LC-MS/MS METHOD FOR ESTIMATION OF UROCARB IN HUMAN PLASMA

2019 ◽  
pp. 125-130
Author(s):  
IRYNA DRAPAK ◽  
BORYS ZIMENKOVSKY ◽  
LINA PEREKHODA ◽  
SERGIY KOVALENKO ◽  
LILIYA LOGOYDA
Keyword(s):  
Formic Acid ◽  
Human Plasma ◽  
Internal Standard ◽  
Sample Volume ◽  
Pharmacokinetic Studies ◽  
Coefficients Of Variation ◽  
Highly Sensitive ◽  
Regulatory Guidelines ◽  
Initial Content ◽  
Development And Validation

Objective: The present study was aimed to develop a rapid, specific and sensitive method based on LC-MS/MS method was developed for the determination of urocarb using etomidate as an internal standard. Methods: Chromatography was achieved on Discovery C18, 50 × 2.1 mm, 5 μm column. Samples were chromatographed in a gradient mode (eluent A (acetonitrile-water–formic acid, 5: 95: 0.1 v/v), eluent B (acetonitrile–formic acid, 100: 0.1 v/v)). The initial content of the eluent B of 8%, which increases linearly to 1.0 min to 100%, is maintained up to 1.5 min and returned to the original 8% to 1.51 min. The mobile phase was delivered at a flow rate of 0.400 ml/min into the mass spectrometer ESI chamber. The sample volume was 4 μl. Results: The total chromatographic run time was 2.0 min and the elution of urocarb and IS (etomidate) occurred at ~1.53 and 1.67 min, respectively. A linear response function was established at 1-100 ng/ml for urocarb and etomidate in human plasma. The % mean recovery for urocarb in LQC, MQC and HQC was 104.1 %, 100.0 % and 97.4 %. The lowest concentration with the RSD<20% was taken as LLOQ and was found to be 1.03 ng/ml for urocarb. The within-run coefficients of variation ranged between 0.271 % and 0.478 % for urocarb. The within-run percentages of nominal concentrations ranged between 99.12 % and 100.21 % for urocarb. The between-run coefficients of variation ranged between 0.388 % and 0.601 % for urocarb. The between-run percentages of nominal concentrations ranged between 98.78 % and 101.11 % for urocarb. Conclusion: A highly sensitive, specific, reproducible, rapid and high-throughput LC-MS/MS assay was developed and validated to quantify urocarb in human plasma as per the regulatory guidelines. Due to the sensitivity of the developed method, it can be applied to the monitoring of plasma levels in the analysis of drug in preclinical and clinical pharmacokinetic studies. All the parameters and results were found within the acceptance limit as given in the validation protocol.

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