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目的:建立一种同时测定人血浆中伊马替尼及其活性代谢产物N-去甲基伊马替尼的高效液相色谱串联质谱(HPLCMS/MS)法,并应用于检测胃肠间质瘤患者伊马替尼及代谢物的浓度。方法:血浆样品经甲醇沉淀蛋白后,以含0.1%甲酸的水溶液和甲醇溶液为流动相;采用梯度洗脱,Waters ACQUITY UPLC BEH C18(2.1 mm×50 mm,1.7μm)色谱柱进行分离,流速为0.3 m L·min~(-1);柱温为35℃。ESI离子源,正离子模式,多反应监测,用于定量分析的离子对为m/z 494.2→m/z 394.3(伊马替尼)、m/z 480.3→m/z 394.3(N-去甲基伊马替尼)、m/z 502.5→m/z 394.4(内标,伊马替尼-D8)。结果:伊马替尼和N-去甲伊马替尼的线性范围均为50~10 000 ng·mL~(-1),定量下限为50 ng·mL~(-1),伊马替尼及代谢物的准确度分别为97.9%~109.0%,95.5%~103.5%,日内和日间变异系数<10%。结论:本方法简便、准确、灵敏、专属性强,适用于人血浆中伊马替尼及其代谢物浓度的检测。
OBJECTIVE: To establish a high performance liquid chromatography tandem mass spectrometry (HPLCMS / MS) method for the simultaneous determination of imatinib and its active metabolite N-desmethyl-imatinib in human plasma and its application in the detection of gastrointestinal stromal Tumor patient imatinib and metabolites concentration. METHODS: The plasma samples were precipitated with methanol and eluted with 0.1% formic acid in water and methanol. The mobile phases were separated on a Waters ACQUITY UPLC BEH C18 (2.1 mm × 50 mm, 1.7 μm) 0.3 m L · min -1. The column temperature was 35 ℃. ESI ion source, positive ion mode, multiple reaction monitoring, ion pair for quantitative analysis m / z 494.2 → m / z 394.3 (imatinib), m / z 480.3 → m / z 394.3 Ki-Imatinib), m / z 502.5 → m / z 394.4 (internal standard, imatinib-D8). RESULTS: The linear range of imatinib and n-desmethyl-imatinib was 50 ~ 10 000 ng · mL -1, the lower limit of quantitation was 50 ng · mL -1, And the accuracy of metabolites were 97.9% -109.0% and 95.5% -103.5%, respectively. The intra-and inter-day coefficient of variation was <10%. Conclusion: The method is simple, accurate, sensitive and specific. It is suitable for the detection of imatinib and its metabolites in human plasma.