Quantification and pharmacokinetics of crizotinib in rats by liquid chromatography-tandem mass spectrometry
Quantification and pharmacokinetics of crizotinib in rats by liquid chromatography-tandem mass spectrometry
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液相色谱-串联质谱法定量克唑替尼在大鼠体内的药代动力学
DOI：
10.1002/bmc.3636
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发表时间：
2016-06-01
影响因子：
1.8
通讯作者：
Cheng, Shan
中科院分区：
文献类型：
--
作者：
Qiu, Feng;Gu, Yanan;Cheng, Shan
克唑替尼是间变性淋巴瘤激酶（ALK）的小分子抑制剂，可用于治疗ALK阳性的非小细胞肺癌。建立了一种快速简便的高效液相色谱-串联质谱（LC-MS/MS）方法，以化学合成化合物丁螺环酮为内标（IS）定量大鼠血浆中克唑替尼的含量。血浆样品用甲醇-乙腈（1:1,v/v）进行简单蛋白沉淀预处理。在Agilent Zorbax XDB C-18色谱柱（2.1x50mm, 3.5 μ m）上成功实现色谱分离。梯度洗脱体系由0.1%甲酸水溶液和0.1%甲酸甲醇溶液组成。流速设定为0.50mL/min。多反应监测基于克唑替尼m/z=450.3177.1和丁螺环酮（IS） m/z= 386.2122.2的过渡。方法的选择性、基质效应、线性、定量下限、准确度、精密度、回收率和稳定性均符合国际标准。50L大鼠血浆中定量下限为1.00ng/mL。该LC-MS/MS方法成功应用于大鼠静脉和口服克唑替尼后克唑替尼的定量和药代动力学研究。克唑替尼大鼠口服绝对生物利用度为68.6±9.63%。版权所有：John Wiley & Sons， Ltd
Crizotinib is a small molecule inhibitor of anaplastic lymphoma kinase (ALK) and can be used to treat ALK-positive nonsmall-cell lung cancer. A rapid and simple high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of crizotinib in rat plasma using a chemical synthetic compound buspirone as the internal standard (IS). The plasma samples were pretreated by a simple protein precipitation with methanol-acetonitrile (1:1, v/v). Chromatographic separation was successfully achieved on an Agilent Zorbax XDB C-18 column (2.1x50mm, 3.5 mu m). The gradient elution system was composed of 0.1% formic acid aqueous solution and 0.1% formic acid in methanol solution. The flow rate was set at 0.50mL/min. The multiple reaction monitoring was based on the transitions of m/z=450.3177.1 for crizotinib and 386.2122.2 for buspirone (IS). The assay was successfully validated to demonstrate the selectivity, matrix effect, linearity, lower limit of quantification, accuracy, precision, recovery and stability according to the international guidelines. The lower limit of quantification was 1.00ng/mL in 50L of rat plasma. This LC-MS/MS assay was successfully applied to the quantification and pharmacokinetic study of crizotinib in rats after intravenous and oral administration of crizotinib. The oral absolute bioavailability of crizotinib in rats was 68.6 +/- 9.63%. Copyright (c) 2015 John Wiley & Sons, Ltd.