A novel LC–MS/MS method for the determination of ziritaxestat in rat plasma and its pharmacokinetic study |
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Authors: | Jing Chen Zhenhua Guan Na Dong Xueliang Li |
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Institution: | 1. Department of Gastroenterology, The First People‘s Hospital of Lianyungang, Lianyungang, Jiangsu Province, China;2. Department of Nursing, Hebei Women's Vocational College, Shijiazhuang, Hebei Province, China |
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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 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 the 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 0.5–2000 ng/ml, with correlation coefficient >0.9987. The extraction recovery was >82.09% and the matrix effect was not significant. Inter- and intra-day precisions (RSD) were <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 a short half-life (~3 h) and low bioavailability (20.52%). |
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Keywords: | bioavailability liquid chromatography tandem mass spectrometry pharmacokinetics rat ziritaxestat |
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