A rugged and accurate liquid chromatography-tandem mass spectrometry method for the determination of asunaprevir, an NS3 protease inhibitor, in plasma.

J Chromatogr B Analyt Technol Biomed Life Sci

Analytical and Bioanalytical Development, Research and Development, Bristol-Myers Squibb, Princeton, NJ 08543, United States.

Published: March 2013

AI Article Synopsis

  • * A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to measure asunaprevir levels in plasma from various animals (rats, dogs, monkeys, rabbits, and mice), ensuring accurate and reliable results.
  • * The method showed precise measurements (intra-assay precision within ±3.6% CV) and was effective for pre-clinical studies on asunaprevir's toxicokinetics across different species.

Article 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.

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http://dx.doi.org/10.1016/j.jchromb.2013.01.029DOI Listing

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