title: 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.
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.
authors.affiliation: Laboratory of Pharmacy Practice and Social Science, Gifu Pharmaceutical University, Gifu, Japan.|Department of Pharmacy, Gifu University Hospital, Gifu, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Laboratory of Pharmacy Practice and Social Science, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Kita
authors.affiliation: Laboratory of Pharmacy Practice and Social Science, Gifu Pharmaceutical University, Gifu, Japan.|Department of Pharmacy, Gifu University Hospital, Gifu, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Iihara
authors.affiliation: Second Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Koumei
authors.initials: K
authors.lastname: Yanase
authors.affiliation: Second Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ohno
authors.affiliation: Department of Pharmacy, Gifu University Hospital, Gifu, Japan.
authors.forename: Chiemi
authors.initials: C
authors.lastname: Hirose
authors.affiliation: Department of Pharmacy, Gifu University Hospital, Gifu, Japan.
authors.forename: Maya
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Department of Analytical and Bio-Analytical Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Todoroki
authors.affiliation: Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Kiyoyuki
authors.initials: K
authors.lastname: Kitaichi
authors.affiliation: Second Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Minatoguchi
authors.affiliation: Department of Pharmacy, Gifu University Hospital, Gifu, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Itoh
authors.affiliation: Laboratory of Pharmacy Practice and Social Science, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Sugiyama
mesh_terms: D000077716:Afatinib; D002138:Calibration; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy*; D002853:Chromatography, Liquid / Q000379:methods; D000069347:Erlotinib Hydrochloride / Q000097:blood*; D000077156:Gefitinib; D006801:Humans; D057230:Limit of Detection; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy*; D011799:Quinazolines / Q000097:blood*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D011799:Quinazolines; D000077716:Afatinib; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib
keywords: LC-MS/MS; afatinib; erlotinib; gefitinib; therapeutic drug monitoring