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.

Determination of Acotiamide in human plasma by LC-MS/MS and its application to a pharmacokinetic study

2020 ◽  
Vol 17 ◽  
Author(s):  
Qian Sun ◽  
Qiao-gen Zou ◽  
Yun-yan Xia ◽  
Cheng-qun Han
Keyword(s):  
Human Plasma ◽  
Pharmacokinetic Study ◽  
Ammonium Acetate ◽  
Internal Standard ◽  
Rat Plasma ◽  
Pharmacokinetic Studies ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass ◽  
Tandem Mass Spectrometric

Background: A liquid chromatography-tandem mass spectrometric (LC-MS/MS) method had been developed for the quantification of acotiamide in rat plasma and been applied to pharmacokinetic studies. However, there was no LC-MS/MS method been developed for the determination of acotiamide in human plasma and its pharmacokinetic study. Objective: A simple and fast LC-MS/MS method was established and validated for the quantification of acotiamide in human Received: plasma and was applied to a pharmacokinetic study. Methods: Sample preparation was accomplished Revised: Accepted: through protein precipitation, and chromatographic separation was achieved on a Welch, Ultimate XB-C18 column (2.1×50 mm, 3 μm) with a security guard cartridge C18 using a binary gradient with DOI: mobile phase A (Methanol) and B (the solution of 10 mM Ammonium acetate with 0.1% Formic acid) at a flow rate of 400 Results: The retention time of acotiamide and its internal standard, acotiamide-d6 was 1.78 min and 1.79 min, respectively. The total run time was 4.0 min. The method was developed and validated over the concentration range of 0.500-100 ng/mL for acotiamide, with correlation coefficient greater than 0.9987. The extraction recovery was more than 108.43% and the matrix effect was not significant. The inter- and intra-day precisions were below 5.80% and accuracies ranged from 92.7 to 103.0%. Acotiamide was demonstrated to be stable in human plasma under the tested conditions. Conclusion: The validated LC-MS/MS method was successfully applied to study the pharmacokinetic profiles of acotiamide in human plasma after oral administration and has achieved satisfactory results.

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

2012 ◽  
Vol 9 (2) ◽  
pp. 899-911 ◽  
Author(s):  
D. Chandrapal Reddy ◽  
A. T. Bapuji ◽  
V. Surayanarayana Rao ◽  
V. Himabindu ◽  
D. Rama Raju ◽  
...  
Keyword(s):  
Human Plasma ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Pharmacokinetic Parameters ◽  
Liquid Liquid Extraction ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Edta Plasma ◽  
Development And Validation

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.

An LC-MS/MS Validated Method for Quantification of Chlorzoxazone in Human Plasma and Its Application to a Bioequivalence Study

2019 ◽  
Vol 57 (8) ◽  
pp. 751-757
Author(s):  
Jiake He ◽  
Ning Li ◽  
Jiaqiu Xu ◽  
Jing Zhu ◽  
Yang Yu ◽  
...  
Keyword(s):  
Human Plasma ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Bioequivalence Study ◽  
Therapeutic Drug ◽  
Reference Formulation ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
One Step

Abstract A simple, sensitive, specific, accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for determination of chlorzoxazone in human plasma was developed and validated to evaluate the pharmacokinetic characteristics of chlorzoxazone test or reference formulation. Sample preparation was achieved by one step protein precipitation and dilution with acetontrile. The chromatographic separation was performed at 40°C with a gradient mobile phase (0.3 mL/min) and a Shimadzu VP-ODS C18 analytical column (column size: 150 × 2.0 mm). TSQ quantum access triple-quadrapole MS/MS detection was operated in a negative mode by multiple reaction monitoring. Ion transitions at m/z 168.0→132.1 for chlorzoxazone and m/z 451.3→379.3 for repaglinide (internal standard) were used for the LC-MS/MS analysis. The calibration was linear (r ≥ 0.995) over the tested concentration range of 0.2–20 μg/mL for chlorzoxazone in plasma. Precision, accuracy, recovery, matrix effect and stability for chlorzoxazone were evaluated and were excellent within the range of tested concentrations. This method was successfully applied to a bioequivalence study in 20 healthy Chinese volunteers. This method could also contribute to the personalized medication and therapeutic drug monitoring of chlorzoxazone.

scholarly journals High-Performance Liquid Chromatography/Tandem Mass Spectrometry Method for the Determination of Arbidol in Human Plasma

2011 ◽  
Vol 94 (4) ◽  
pp. 1100-1105 ◽  
Author(s):  
Xin Xiong ◽  
Suodi Zhai
Keyword(s):  
Human Plasma ◽  
High Performance ◽  
Internal Standard ◽  
Sample Volume ◽  
Tandem Mass ◽  
Spectrometry Method ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Butyl Methyl Ether

Abstract An HPLC/MS/MS method for the determination of arbidol in human plasma was developed. Arbidol and internal standard (loratadine) were extracted from alkaline plasma with tert-butyl methyl ether and analyzed on a Zorbax SB C18 column (30 × 2.1 mm id, 3.5 µm particle size). The detection was by monitoring arbidol at m/z 479.1 → 434.1 and the internal standard at m/z 383.2 → 337.2. The method was validated according to U.S. Food and Drug Administration guidelines. The calibration curve was linear over the range of 0.5–500 ng/mL using a 100 µL sample volume. The intraday and interday precisions were less than 6.5%, and acceptable values were obtained for accuracy, recovery, and sensitivity. The developed method was selective, simple, sensitive, and easily applicable.

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