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Simultaneous and rapid determination of gefitinib, erlotinib and afatinib plasma levels using liquid chromatography/tandem mass spectrometry in patients with non‐small‐cell lung cancer
Author(s) -
Hayashi Hideki,
Kita Yutaro,
Iihara Hirotoshi,
Yanase Koumei,
Ohno Yasushi,
Hirose Chiemi,
Yamada Maya,
Todoroki Kenichiro,
Kitaichi Kiyoyuki,
Minatoguchi Shinya,
Itoh Yoshinori,
Sugiyama Tadashi
Publication year - 2016
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.3642
Subject(s) - afatinib , chemistry , chromatography , erlotinib , tandem mass spectrometry , lung cancer , pharmacokinetics , protein precipitation , electrospray ionization , mass spectrometry , liquid chromatography–mass spectrometry , therapeutic drug monitoring , pharmacology , epidermal growth factor receptor , oncology , medicine , biochemistry , receptor
A simultaneous, selective, sensitive and rapid liquid chromatography/tandem mass spectrometry method was developed and validated for the quantification of gefitinib, erlotinib and afatinib in 250 μL samples of human blood plasma. Diluted plasma samples were extracted using a liquid‐phase extraction procedure with tert ‐butyl methyl ether. The three drugs were separated by high‐performance liquid chromatography using a C 18 column and an isocratic mobile phase running at a flow rate of 0.2 mL/min for 5 min. The drugs were detected using a tandem mass spectrometer with electrospray ionization using imatinib as an internal standard. Calibration curves were generated over the linear concentration range of 0.05–100 n m in plasma with a lower limit of quantification of 0.01 or 0.05 n m for all compounds. Finally, the validated method was applied to a clinical pharmacokinetic study in patients with nonsmall‐cell lung cancer (NSCLC) following the oral administration of afatinib. These results indicate that this method is suitable for assessing the risks and benefits of chemotherapy in patients with NSCLC and is useful for therapeutic drug monitoring for NSCLC treatment. As far as we know, this is the first report on LC‐MS/MS method for the simultaneous quantification of NSCLC tyrosine kinase inhibitor plasma concentrations including afatinib. Copyright © 2015 John Wiley & Sons, Ltd.