A rugged and accurate liquid chromatography–tandem mass spectrometry method for quantitative determination of BMS-790052 in plasma

Abstract

To support toxicokinetic assessments, a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for the quantification of BMS-790052 in rat, dog, monkey, rabbit and mouse K 2EDTA plasma. The drug was isolated from buffered samples using ISOLUTE C8 96-well solid phase extraction (SPE) plates. Chromatographic separation was achieved on a Waters Atlantis dC18 analytical column (2.1 mm × 50 mm, 5 μm) with detection accomplished using an API 4000 tandem mass spectrometer in positive ion electrospray and multiple reaction monitoring (MRM) mode. The standard curves, which ranged from 5.00 to 2000 ng/mL for BMS-790052, were fitted to a 1/ x 2 weighted linear regression model. The intra-assay precision (%CV) and inter-assay precision (%CV) were within 8.5%, and the assay accuracy (%Dev) was within ±7.1 for rat, dog, monkey, rabbit and mouse K 2EDTA plasma. This accurate, precise, and selective SPE/LC–MS/MS method has been successfully applied to analyze several thousands of non-clinical study samples.