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Current Pharmaceutical Analysis

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ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

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Research Article

Simultaneous Bioanalysis of Prodrug Oseltamivir and its Metabolite Oseltamivir Carboxylic Acid in Human Plasma by LC/MS/MS Method and its Application to Disposition Kinetics

Author(s): Dodda Sireesha*, Makula Ajitha and Kandhagatta Raj Narayana

Volume 16, Issue 2, 2020

Page: [143 - 152] Pages: 10

DOI: 10.2174/1573412914666181011125120

Price: $65

Abstract

Introduction: A selective, sensitive, precise and rapid analytical method using liquid chromatography- tandem mass spectrometry (LC/MS/MS) for simultaneous determination of oseltamivir and oseltamivir carboxylic acid in plasma has been developed and validated, using oseltamivir-D5 and oseltamivir acid-D3 as internal standards.

Methods: The analytes were extracted from 300μL of human plasma using solid phase extraction technique. A mixture of methanol and 0.1% formic acid (60:40, v/v) was used as mobile phase at a flow rate of 0.7mL/min, to separate the analytes on Zorbax SB-C18 (50x4.6mm, 3.5μm) analytical column.

Results: The calibration curves obtained were linear over the concentration ranges of 0.5-200ng/mL and 2.0-800ng/mL for oseltamivir and oseltamivir carboxylic acid respectively. A run time of 2.5min makes it possible to analyze more than 350 plasma samples in a day, thereby increasing the productivity.

Conclusion: The present method was applied successfully to a clinical pharmacokinetic study in South Indian male subjects with 75mg oseltamivir phosphate capsule under fasting conditions and the results were authenticated by incurred sample reanalysis.

Keywords: Oseltamivir, oseltamivir carboxylic acid, bioanalytical method, LC/MS/MS, pharmacokinetics, disposition kinetics.

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