超高效液相色谱-质谱法测定人血浆中伊马替尼的浓度

Determination of imatinib in human plasma by UPLC-MS/MS

目的建立超高效液相色谱-质谱(UPLC-MS/MS)法测定血浆中伊马替尼浓度的方法。方法以卡马西平为内标,用蛋白沉淀前处理方法。色谱柱为ACQUITY UPLC BEH C_(18)(100 mm×2.1 mm,1.7μm),流动相为乙腈-0.1%甲酸水溶液(25∶75),流速为0.4 m L·min^(-1),正离子模式多反应监测(MRM)扫描分析,并考察专属性、标准曲线与定量下限、精密度与回收率、基质效应和稳定性。结果血浆中伊马替尼线性范围为0.1~20.0μg·m L^(-1)(r=0.996),定量下限为0.1μg·m L^(-1),提取回收率在95.25%~98.21%,日内、日间精密度相对标准偏差(RSD)均小于15%。结论该法操作简便快速,特异性强,灵敏度高,可用于伊马替尼的治疗药物浓度监测。

Objective To establish the UPLC- MS / MS method for the determination of imatinib in human plasma. Methods The plasma procedure involved a single- step protein precipitation by acetonitrile.The samples were separated by a ACQUITY UPLC BEH C_（18） column（ 100 mm × 2. 1 mm,1. 7 μm） using a mobile phase consisted of acetonitrile- 0. 1% formic acid（ 25： 75） at a flow rate of 0. 4 m L · min^-1. The protonated ions of analytes were detected in positive ionization in multiple reaction monitoring mode（ MRM）. The specificity,standard curve,lower limit of quantitation,precision,recovery rate and stability as well as the matrix effect were investigated. Results The calibration curve was linear over a concentration range of 0. 1 to 20. 0 μg · m L^-1（ r = 0. 996） and the low limit of quantitation was 0. 1 μg·m L^-1. The extraction recovery rates were ranged from 95. 25% to 98. 21%,with- day RSD and between- day RSD were all less than 15%.Conclusion The method is simple and quick,with high specificity and sensitivity, and suitable for clinical therapeutic drug monitoring of imatinib.