1. Academic Validation
  2. 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

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

  • Biomed Chromatogr. 2016 Jul;30(7):1150-1154. doi: 10.1002/bmc.3642.
Hideki Hayashi 1 2 Yutaro Kita 1 Hirotoshi Iihara 1 2 Koumei Yanase 3 Yasushi Ohno 3 Chiemi Hirose 2 Maya Yamada 2 Kenichiro Todoroki 4 Kiyoyuki Kitaichi 5 Shinya Minatoguchi 3 Yoshinori Itoh 2 Tadashi Sugiyama 1
Affiliations

Affiliations

  • 1 Laboratory of Pharmacy Practice and Social Science, Gifu Pharmaceutical University, Gifu, Japan.
  • 2 Department of Pharmacy, Gifu University Hospital, Gifu, Japan.
  • 3 Second Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
  • 4 Department of Analytical and Bio-Analytical Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
  • 5 Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan.
Abstract

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 C18 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 nm in plasma with a lower limit of quantification of 0.01 or 0.05 nm 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.

Keywords

LC-MS/MS; afatinib; erlotinib; gefitinib; therapeutic drug monitoring.

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