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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

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机构: [1]Sun Yat Sen Univ, Inst Clin Pharmacol, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China; [2]Sun Yat Sen Univ, State Key Lab Oncol South China, Dept Gastr & Pancreat Surg, Collaborat Innovat Ctr Canc Med,Canc Ctr, Guangzhou, Guangdong, Peoples R China; [3]Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China; [4]Dept Gastr & Pancreat Surg, Collaborat Innovat, State Key Lab Oncol S China, Guangzhou, Guangdong, Peoples R China
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关键词: GIST imatinib LC-MS/MS N-demethyl-imatinib pharmacokinetics

摘要:
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 (50x2.1mm i.d., 3.5m) 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 0.2mL/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 494.0394.0 for imatinib, m/z 479.6394.0 for NDI and m/z 488.2394.0 for IS. The method was linear over 0.01-10g/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 10ng/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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出版当年[2017]版:
大类 | 4 区 生物
小类 | 4 区 生化研究方法 4 区 生化与分子生物学 4 区 分析化学 4 区 药学
最新[2023]版:
大类 | 4 区 医学
小类 | 4 区 生化研究方法 4 区 生化与分子生物学 4 区 分析化学 4 区 药学
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第一作者机构: [1]Sun Yat Sen Univ, Inst Clin Pharmacol, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China;
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通讯机构: [1]Sun Yat Sen Univ, Inst Clin Pharmacol, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China; [2]Sun Yat Sen Univ, State Key Lab Oncol South China, Dept Gastr & Pancreat Surg, Collaborat Innovat Ctr Canc Med,Canc Ctr, Guangzhou, Guangdong, Peoples R China; [4]Dept Gastr & Pancreat Surg, Collaborat Innovat, State Key Lab Oncol S China, Guangzhou, Guangdong, Peoples R China
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