Simultaneous determination of gefitinib and its major metabolites in mouse plasma by HPLC-MS/MS and its application to a pharmacokinetics study

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Nan ZhengPing-Ping Li

Abstract

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 6min 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 0.5-100ng/mL for M608236 and 1-200ng/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 meth...Continue Reading

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Citations

May 31, 2020·Endocrinology·Brittany M DugganJonathan D Schertzer
Aug 7, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Ying LiGuohui Li
Jul 5, 2021·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Nikunj TannaRobert S Plumb
Dec 31, 2021·Journal of Proteome Research·Robert S PlumbIan D Wilson

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