Simultaneous quantification of prodrug oseltamivir and its metabolite oseltamivir carboxylate in human plasma by LC-MS/MS to support a bioequivalence study

详细信息    查看全文

• 作者：Ajay Gupta ; Swati Guttikar ; Pranav S. Shrivastav ; Mallika Sanyal
• 关键词：Oseltamivir ; Oseltamivir carboxylate ; LC-MS/MS ; Human plasma ; Bioequivalence study
• 刊名：Journal of Pharmaceutical Analysis
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：3
• 期：3
• 页码：149-160
• 全文大小：1621 K

文摘

A simple, precise and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the simultaneous determination of oseltamivir and oseltamivir carboxylate, a neuraminidase inhibitor, using their deuterated analogs as internal standards (ISs). The method involved solid phase extraction of the analytes and ISs from 200 ¦ÌL human plasma with no reconstitution and drying steps. The chromatographic separation was achieved on a Symmetry C18 (100 mm¡Á4.6 mm, 5 ¦Ìm) column using 10 mM ammonium formate and acetonitrile (30:70, v/v) as the mobile phase in a run time of 2.0 min. Quantitation of analytes and ISs were done by multiple reaction monitoring on a triple quadrupole mass spectrometer in the positive ionization mode. The linearity of the method was established in the concentration range of 0.5-200 ng/mL and 2.0-800 ng/mL for oseltamivir and oseltamivir carboxylate respectively. The mean extraction recovery for oseltamivir (94.4 % ) and oseltamivir carboxylate (92.7 % ) from spiked plasma samples was consistent and reproducible. The application of this method was demonstrated by a bioequivalence study in 42 healthy Indian subjects with 75 mg oseltamivir phosphate capsules. The assay reproducibility was established by reanalysis of 151 incurred subject samples.