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Simultaneous quantification of imatinib and its main metabolite N‐demethyl‐imatinib in human plasma by liquid chromatography–tandem mass spectrometry and its application to therapeutic drug monitoring in patients with gastrointestinal stromal tumor
Author(s) -
Zhuang Wei,
Qiu HaiBo,
Chen XinMeng,
Yuan XiuHong,
Yang LiFang,
Sun XiaoWei,
Zhou XiaoJun,
Huang Min,
Wang XueDing,
Zhou ZhiWei
Publication year - 2017
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.4022
Subject(s) - chemistry , chromatography , selected reaction monitoring , formic acid , imatinib , mass spectrometry , tandem mass spectrometry , metabolite , imatinib mesylate , liquid chromatography–mass spectrometry , electrospray ionization , detection limit , therapeutic drug monitoring , active metabolite , analyte , pharmacokinetics , pharmacology , medicine , biochemistry , myeloid leukemia , immunology , biology
The aim of this study was to improve and validate a more stable and less time‐consuming method based on liquid chromatography and tandem mass spectrometry (LC‐ MS/MS) for the quantitative measurement of imatinib and its metabolite N‐ demethyl‐imatinib (NDI) in human plasma. Separation of analytes was performed on a Waters XTerra RP 18 column (50 × 2.1 mm i.d., 3.5 μm) with a mobile phase consisting of methanol–acetonitrile–water (65:20:15, v /v/v) with 0.05% formic acid at a flow‐rate of 0.2 mL/min. The Quattro MicroTM triple quadruple mass spectrometer was operated in the multiple‐reaction‐monitoring mode via positive electrospray ionization interface using the transitions m / z 494.0 → 394.0 for imatinib, m / z 479.6 → 394.0 for NDI and m / z 488.2 → 394.0 for IS. The method was linear over 0.01–10 μg/mL for imatinib and NDI. The intra‐ and inter‐day precisions were all <15% in terms of relative standard deviation, and the accuracy was within ±15% in terms of relative error for both imatinib and NDI. The lower limit of quantification was identifiable and reproducible at 10 ng/mL. The method was sensitive, specific and less time‐consuming and it was successfully applied in gastrointestinal stromal tumor patients treated with imatinib.