HPLC-MS/MS法同时测定大鼠血浆中水飞蓟宾A和水飞蓟宾B及其药代动力学研究  

HPLC-MS/MS study on pharmacokinetics of silybin A and silybin B in rat plasma

作　　者：罗学军[1,2] 李伟[2] 韩建平[2] 褚杨[2] 黄艳萍[1] 

机构地区：[1]天津医科大学药学院,天津300070 [2]天津天士力集团研究院,天津300410

出　　处：《药物分析杂志》2009年第12期2002-2006,共5页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立大鼠血浆中水飞蓟宾A和水飞蓟宾B的测定法,并用于大鼠体内的药代动力学研究。方法:采用静脉给药方式,蛋白沉淀法快速制备样品;分析柱为Agilent Zorbax Eclipse XDB-C18(150mm×2.1mm,5μm),流动相为甲醇-0.1%的甲酸溶液(48∶52);质谱条件为ESI(-)电离方式,扫描方式为选择性反应监测(SRM),范围m/z481.1→300.9(水飞蓟宾A和B)和m/z579.2→271.1(内标)。结果:分析方法的线性范围水飞蓟宾A和B均为20～50000ng·mL-1,样品的检出限均为20ng·mL-1,日内和日间精密度均≤9.1%,准确度在±5.8%之内,方法的回收率均在90%以上。药代动力学研究结果表明水飞蓟宾A和B在大鼠体内的动力学过程均符合二室模型。对参数计算结果进行非参数检验,显示其在水飞蓟宾A和B间均无显著性差异,表明二者在大鼠体内有相似的药代动力学行为。结论:本方法简单、灵敏、稳定可靠,适合于水飞蓟宾、水飞蓟素及其制剂的药代动力学研究。Objective：To establish an LC-MS/MS method for determination of silybin A and silybin B to study their pharmacokinetics in rat plasma.Method：Intravenous administration was used and a simplified protein precipitation with acetonitrile was employed for the rapid sample preparation;The separation was achieved on a Zorbax Eclipse XDB-C18 column（150 mm×2.1 mm,5 μm）,using methanol-water containing 0.1% formic acid （48∶52） as the mobile phase.With negative electrospray ionization;The mass spectrometer was operated in selected reaction monitoring （SRM） mode using the transition m/z 481.1→300.9 for both silybin A and silybin B and m/z 579.2→271.1 for naringin,respectively.Result：Linear calibration curves were obtained in the concentration range of 20-50000 ng·mL-1 with a lower limit of quantitation of 20 ng·mL-1 for both silybin A and silybin B,respectively;The intra-and inter-day precision values were below 9.1% and accuracy was within ±5.8% at all three quality control levels,and the recovery of assay were above 90% for both silybin A and silybin B,respectively;Mean plasma concentration-time curves of both silybin A and silybin B were best fitted to two-compartment models in rat.The pharmacokinetic parameters between silybin A and B were no significant difference.It shows that there is a similar pharmacokinetic behavior between silybin A and B in rats plasma.Conclusion：The validated method is simple,sensitive,selective and reproducible for the study of the pharmaeokineties of silybin,silymarin or their preparations.

关 键 词：水飞蓟宾A 水飞蓟宾B 液-质联用 药代动力学 

分 类 号：R917[医药卫生—药物分析学]