LC-MS/MS法测定乳腺癌患者血浆中拉帕替尼浓度  

Determination of lapatinib concentration in plasma of breast cancer patients by LC-MS/MS

作　　者：黄越[1] 项迎春[1] 韩奇[1] 李力[1] HUANG Yue;XIANG Ying-chun;HAN QI;LI Li(Depat merit of Pharmacy,Zhejiang Hospital,Hangzhou 310013,Zhejiang Province,China)

机构地区：[1]浙江医院药剂科,浙江杭州310013

出　　处：《中国临床药理学杂志》2022年第6期585-588,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家科技重大专项项目-老年病新药临床技术平台基金资助项目(2013ZX09303005);浙江省自然科学基金资助项目(LQ15H310003)。

摘　　要：目的建立一种快速、灵敏的液相色谱-串联质谱(LC-MS/MS)法检测乳腺癌患者血浆中拉帕替尼的浓度。方法以厄洛替尼为内标,血浆样品经乙腈直接沉淀蛋白后,经CAPCELL PAK-C;(50 mm×100 mm,3.5μm)色谱柱分离,流动相为乙腈-水(均含0.1%甲酸水)(88∶12,v/v),柱温30℃,分析时间3 min。用电喷雾离子化源,正离子方式,多反应监测(MRM)模式。方法验证内容包括专属性、标准曲线与定量下限、精密度与准确度、基质效应、稳定性。结果拉帕替尼在0.02~5.0μg·mL^(-1)线性关系良好(r=0.9943);标准曲线方程为Y=2.38X-4.85×10^(-3),最低定量下限和低、中、高浓度的准确度在94.0%~106.0%;批内和批间RSD均小于15%;拉帕替尼和内标的提取回收率85.2%~94.6%,低、中、高质量浓度的基质效应分别为96.0%,103.1%和105.0%,稳定性考察项目均符合要求。结论建立的LC-MS/MS方法特异性强,灵敏度高,可以满足临床药物监测及药代动力学研究的需要。Objective To devolope a liquid chromatography-tandem mass spectrometry(LC-MS/MS) method for the determination of lapatinib in breast cancer patients. Methods Erlotinib was used as the internal standard.The analyte and internal standard were extracted from plasma by protein precipitation with acetonitrile and chromatographedon CAPCELL PAK-C;(50 mm×100 mm, 3.5 μm),mobile phase was consisted of acetonitrile-water(both of containing 0.1% formic acid), The column temperature was 30 ℃,the whole analytical time was 3 min.Electrospray ionization(ESI) source was applied and operatedin the positive multiple reaction monitoring(MRM) mode. The selectivity standard curve, precision and accuracy, extraction recoveries, matrix effect and stability were investigated. Results The standard curves were demonstrated to be liner in the range of 0.02-5.0 μg·mL^(-1)(r=0.994 3), the RSD of inter-day and intra-day for four different concentration levels were less than 15%,The mean extract recoveries were between 85.2% and 94. 6%.The matrix effects of LQC, MQC and HQC were 96.0%,103.1% and 105.0% respectively, all stability tests met theacceptance criteria. Conclusion The method is specific, sensitive and suitable for clinical determination of lapatinib in breast patients plasma efficiently,suitable for the pharmacokinetic study of and the monitoring of plasma concentration.

关 键 词：拉帕替尼 液质联用法 血药浓度 

分 类 号：R97[医药卫生—药品]