Qiu Feng, Gu Yanan, Wang Tingting, Gao Yingying, Li Xiao, Gao Xiangyu, Cheng Shan
Beijing Key Laboratory of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.
Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, 100069, China.
Biomed Chromatogr. 2016 Jun;30(6):962-8. doi: 10.1002/bmc.3636. Epub 2015 Nov 23.
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 C18 column (2.1 × 50 mm, 3.5 µm). 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 0.50 mL/min. The multiple reaction monitoring was based on the transitions of m/z = 450.3 → 177.1 for crizotinib and 386.2 → 122.2 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 1.00 ng/mL in 50 μL 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 © 2015 John Wiley & Sons, Ltd.
克唑替尼是一种间变性淋巴瘤激酶（ALK）小分子抑制剂，可用于治疗ALK阳性非小细胞肺癌。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作为内标（IS），用于定量大鼠血浆中的克唑替尼。血浆样品通过甲醇 - 乙腈（1:1，v/v）简单蛋白沉淀进行预处理。在安捷伦Zorbax XDB C18柱（2.1×50 mm，3.5 µm）上成功实现了色谱分离。梯度洗脱系统由0.1%甲酸水溶液和0.1%甲酸甲醇溶液组成。流速设定为0.50 mL/min。多反应监测基于克唑替尼的m/z = 450.3→177.1和丁螺环酮（IS）的m/z = 386.2→122.2的跃迁。根据国际指南，该测定法成功验证了其选择性、基质效应、线性、定量下限、准确性、精密度、回收率和稳定性。在50 μL大鼠血浆中的定量下限为1.00 ng/mL。该LC-MS/MS测定法成功应用于克唑替尼静脉和口服给药后大鼠体内克唑替尼的定量和药代动力学研究。克唑替尼在大鼠体内的口服绝对生物利用度为68.6±9.63%。版权所有©2015 John Wiley & Sons, Ltd.
