LC-MS/MS法测定人血浆中表柔比星浓度及其药动学研究  

Determination of Epirubicin Concentration in Human Plasma by LC-MS/MS and Its Pharmacokinetic Study

作　　者：杨润祥[1] 冯恩富[2] 董超[1] 杨芳[1] 董丽春[2] 贺建昌[2] 

机构地区：[1]云南省肿瘤医院肿瘤内二科,昆明650118 [2]成都军区昆明总医院药学部,昆明650032

出　　处：《中国药房》2014年第46期4355-4357,共3页China Pharmacy

摘　　要：目的：建立测定人血浆中表柔比星浓度的方法并研究其药动学行为。方法：以液-液萃取法进行样品前处理,采用液-质联用法进样测定。色谱柱为Zorbax Eclipse XDB-C18,流动相为甲醇-水（含0.1%甲酸）（55∶45）,流速为0.3 ml/min。电喷雾离子化电离源（ESI）,正离子方式检测,扫描方式为多反应监测（MRM）,用于定量的离子分别为表柔比星m/z 544.2→397.1和柔红霉素（内标）m/z 528→321。结果：表柔比星血药浓度在0.506~202.4 ng/ml范围内线性关系良好,最低定量限（LLOQ）为0.506 ng/ml;提取回收率均〉80%,方法回收率为95.09%~112.93%,日内、日间精密度良好（RSD〈4%）。4名患者应用表柔比星治疗后,药动学参数cmax、t1/2、tmax、AUC0-144 h分别为（37.54±21.13）μg/L、（38.02±7.63）h、（47.00±8.25）h、（1 132.81±414.92）μg·h/L。结论：本方法经考察符合生物样品的分析要求,可以应用于临床上血浆中表柔比星浓度的测定和药动学研究。OBJECTIVE： To develop a method for the determination of epirubicin concentration in human plasma and study its pharmacokinetics. METHODS： After liquid-liquid extraction, plasma samples were determined by LC-MS/MS. The determination was performed on Zorbax Eclipse XDB-C18 column with mobile phase consisted of methanol-water （containing 0.1% formic acid） （55：45） at the flow rate of 0.3 ml/min. The analytes were detected by positive ion electrospray ionization （ESI） in multiple reaction monitoring （MRM） mode, monitoring the transitions m/z 544.2→397.1 and m/z 528→321 for epirubicin and daunorubicin （IS）, re- spectively. RESULTS： The linear range of epirubicin was 0.506-202.4 ng/ml, with lowest limit of quantitation （LLOQ） of 0.506 ng/ ml. The extraction recovery was more than 80%. RSDs of intra-day and inter-day were 4%. Pharmacokinetic parameters of epirubi- cin were as follows： Cmax was （37.54± 21.13）μg/L; t1/2 was （38.02±7.63）h; tmax was（47.00± 8.25）h and AUC0-144h was （1 132.81 ± 414.92） μg·h/L. CONCLUSIONS： The method is in line with the requirements of biological sample analysis and can be used for the determination of plasma concentration and pharmacokinetic study of epirubicin.

关 键 词：液-质联用法 表柔比星 微量泵入 药动学 血药浓度 

分 类 号：R969.1[医药卫生—药理学]