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

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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液相色谱-串联质谱法同时定量人血浆中伊马替尼及其主要代谢物N-去甲基伊马替尼及其在胃肠道间质瘤患者治疗药物监测中的应用

DOI:
10.1002/bmc.4022
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发表时间:
2017-12-01
影响因子:
1.8
通讯作者:
Zhou, Zhi-Wei
Zhou, Zhi-Wei
中科院分区:
医学4区
文献类型:
--
作者:
Zhuang, Wei;Qiu, Hai-Bo;Zhou, Zhi-Wei

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本研究旨在改进和验证一种更稳定、更省时的液相色谱-串联质谱(LC- MS/MS)定量测定人血浆中伊马替尼及其代谢物n -去甲基伊马替尼(NDI)的方法。色谱柱为Waters XTerra RP18 (50x2.1mm,直径3.5m),流动相为甲醇-乙腈-水(65:20:15,v/v/v),流速为0.05%甲酸,流速为0.2mL/min。Quattro MicroTM三重四重质谱联用仪采用正电喷雾电离界面,以m/z 494.0394.0(伊马替尼)、m/z 479.6394.0 (NDI)和m/z 488.2394.0 (IS)为过渡段,在多反应监测模式下运行。伊马替尼和NDI在0.01 ~ 10g/mL范围内线性关系良好。一天之内和一天之间的精确度都是
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