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A rugged and accurate liquid chromatography–tandem mass spectrometry method for the determination of asunaprevir, an NS3 protease inhibitor, in plasma
- Source :
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Journal of Chromatography B: Analytical Technologies in the Biomedical & Life Sciences . Mar2013, Vol. 921-922, p81-86. 6p. - Publication Year :
- 2013
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Abstract
- Abstract: Asunaprevir (BMS-650032) is a potent hepatitis C virus (HCV) non-structural protein protease inhibitor currently in Phase III clinical trials for the treatment of HCV infection. A rugged and accurate LC–MS/MS method was developed and validated for the quantitation of asunaprevir in rat, dog, monkey, rabbit and mouse plasma. A systematic method screening and optimization strategy was applied to achieve optimized mass spectrometry, chromatography, and sample extraction conditions. The validated method utilized stable-isotope labeled D9-asunaprevir as the internal standard. The samples were extracted by liquid–liquid extraction using 10% ethyl acetate in hexane. Chromatographic separation was achieved with gradient elution on a Waters Atlantis dC18 analytical column. Analyte and its internal standard were detected by positive ion electrospray tandem mass spectrometry. The standard curve, which ranged from 5.00 to 2000ng/mL for asunaprevir, was fitted to a 1/x 2 weighted linear regression model. The intra-assay precision was within ±3.6% CV, inter-assay precision was within ±4.0% CV, and the assay accuracy was within ±8.1% of the nominal values in all the species. The method was successfully applied to support multiple pre-clinical toxicokinetic studies in different species. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 15700232
- Volume :
- 921-922
- Database :
- Academic Search Index
- Journal :
- Journal of Chromatography B: Analytical Technologies in the Biomedical & Life Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 85903852
- Full Text :
- https://doi.org/10.1016/j.jchromb.2013.01.029