Chen Jing, Guan Zhenhua, Dong Na, Li Xueliang
Department of Gastroenterology, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu Province, China.
Department of Nursing, Hebei Women's Vocational College, Shijiazhuang, Hebei Province, China.
Biomed Chromatogr. 2020 Aug;34(8):e4863. doi: 10.1002/bmc.4863. Epub 2020 May 18.
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 C 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%).
齐立他司他是一种一流的自毒素抑制剂。本研究的目的是开发一种液相色谱/电喷雾电离串联质谱（LC-MS/MS）方法，用于测定大鼠血浆中的齐立他司他。血浆样品用乙腈进行脱蛋白处理，然后在Acquity BEH C柱上进行分离，以含0.1%甲酸的水和乙腈作为流动相，流速为0.4 ml/min。分别以m/z 589.3＞262.2和m/z 450.1＞260.2的母离子到子离子的跃迁对齐立他司他和内标（克唑替尼）进行定量监测。总运行时间为2.5分钟。该方法在0.5 - 2000 ng/ml的浓度范围内显示出良好的线性，相关系数＞0.9987。提取回收率＞82.09%，基质效应不显著。日间和日内精密度（RSD）＜11.20%，准确度在 - 8.50 - 7.45%范围内。在测试条件下，齐立他司他在大鼠血浆中被证明是稳定的。经过验证的LC-MS/MS方法成功应用于研究齐立他司他静脉注射和口服给药后在大鼠血浆中的药代动力学特征。药代动力学结果表明，齐立他司他的半衰期较短（约3小时），生物利用度较低（20.52%）。
