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

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EarlyView Article

  • Published: Aug 7, 2017
  • Author: Wei Zhuang, Hai‐Bo Qiu, Xin‐Meng Chen, Xiu‐Hong Yuan, Li‐Fang Yang, Xiao‐Wei Sun, Xiao‐Jun Zhou, Min Huang, Xue‐Ding Wang, Zhi‐Wei Zhou
  • Journal: Biomedical Chromatography


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 RP18 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.

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