J. Chen, Zhenhua Guan, Na Dong
Apr 23, 2020
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Journal
Biomedical chromatography : BMC
Abstract
Ziritaxestat is a first-in-class autotoxin inhibitor. The purpose of this study was to develop a liquid chromatography/electrospray ionization tandem mass spectrometric (LC-MS/MS) method for the determination of ziritaxestat in rat plasma. The plasma sample was deproteinated by using acetonitrile and then separated on an ACQUITY BEH C18 column with water containing 0.1% formic acid and acetonitrile as mobile phase, which was delivered at 0.4 mL/min. Ziritaxestat and internal standard (crizotinib) were quantitatively monitored with precursor-to-product transitions of m/z 589.3 > 262.2 and m/z 450.1 > 260.2, respectively. The total running time was 2.5 min. The method showed excellent linearity over the concentration range of 0.5-2000 ng/mL, with correlation coefficient greater than 0.9987. The extraction recovery was more than 82.09% and the matrix effect was not significant. Inter- and intra-day precisions (RSD%) were below 11.20% and accuracies were in the range of -8.50-7.45%. Ziritaxestat was demonstrated to be stable in rat plasma under the tested conditions. The validated LC-MS/MS method was successfully applied to study the pharmacokinetic profiles of ziritaxestat in rat plasma after intravenous and oral administration. Pharmacokinetic results demonstrated that ziritaxestat displayed short half-life (~3 h) and low bioavailability (20.52%).