Highly sensitive method for the determination of a novel triple kinase inhibitor with anti-cancer activity, JI-101, in rat plasma by liquid chromatography–electrospray ionization tandem mass spectrometry: application to a pharmacokinetic study

摘要

A highly sensitive, rapid assay method has been developed and validated for the estimation of JI-101 in rat plasma with liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive-ion mode. The assay procedure involves extraction of JI-101 and phenacetin (internal standard, IS) from rat plasma with a solid-phase extraction process. Chromatographic separation was achieved using a binary gradient using mobile phase A (acetonitrile) and B (0.2% formic acid in water) at a flow rate of 0.30?mL/min on a Prodigy ODS column with a total run time of 4.0?min. The MS/MS ion transitions monitored were 466.1 → 265 for JI-101 and 180.1 → 110.1 for IS. Method validation and sample analysis were performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 5.03?ng/mL and the linearity range extended from 5.03 to 2014?ng/mL. The intra-day and inter-day precisions were in the ranges of 1.17–19.6 and 3.09–10.4%, respectively. This method has been applied to a pharmacokinetic study of JI-101 in rats. Copyright ? 2010 John Wiley & Sons, Ltd.