Simultaneous determination of gefitinib and its major metabolites in mouse plasma by HPLC-MS/MS and its application to a pharmacokinetics study
Simultaneous determination of gefitinib and its major metabolites in mouse plasma by HPLC-MS/MS and its application to a pharmacokinetics study
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DOI：
10.1016/j.jchromb.2016.01.006
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发表时间：
2016-02-01
影响因子：
3
通讯作者：
Li, Ping-Ping
中科院分区：
文献类型：
--
作者：
Zheng, Nan;Zhao, Can;Li, Ping-Ping
Gefitinib (Iressa) is the first oral EGFR tyrosine kinase inhibitor and it brings benefits to non-small cell lung cancer patients with EGFR mutation. In this study, a simple, rapid and credible high performance liquid chromatography-tandem mass spectrometry method was established and validated for the simultaneous quantification of gefitinib and its main metabolites M523595, M537194, M387783 and M608236 in NSCLC tumor-bearing mouse plasma. Sample extraction was done by protein precipitation using acetonitrile containing dasatinib as the internal standard. The chromatography run time was 6 min using an Agilent RRHD SB-C18 column with a gradient of acetonitrile and water (0.1% formic acid, v/v). The mass analysis was performed by a triple quadrupole mass spectrometry in positive multiple reaction monitoring mode. The calibration range was 0.5-100 ng/mL for M608236 and 1-200 ng/mL for other analytes with the correlation coefficients (r(2)) >= 0.99. For quality control samples, inter- and intra-assay precision was less than 15% and accuracies ranged from 92.6% to 107.58% for all analytes. The extraction recoveries were in the range of 86-105% and no significant matrix effect was observed. This simple and reproducible high throughput method was successfully applied to the pharmacokinetic study of gefitinib and its major metabolites in mouse. (C) 2016 Elsevier B.V. All rights reserved.
