LC-MS/MS法测定人血浆中表柔比星浓度及其药动学研究

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0.506²02.4 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%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。

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

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.