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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 a method for the determination of silybin A and silybin B in rat plasma and to study the pharmacokinetics in rats. Methods: The samples were rapidly prepared by intravenous administration and protein precipitation method. The analytical column was Agilent Zorbax Eclipse XDB-C18 (150mm × 2.1mm, 5μm) with a mobile phase of methanol-0.1% formic acid solution (48:52) The conditions were ESI (-) ionization and scanning mode was selective reaction monitoring (SRM) in the range of m / z 481.1 → 300.9 (silybin A and B) and m / z 579.2 → 271.1 (internal standard). Results: The linear range of the analytical method was 20 ~ 50000 ng · mL-1 for silybin A and 20 ng · mL-1 for the silybin. The intra-and inter-day precision was ≤9.1%, and the accuracy Within ± 5.8%, the recovery rates of the methods are above 90%. Pharmacokinetic study results showed that silybin A and B in rats kinetics are in line with the two-compartment model. Nonparametric tests on the calculated results of the parameters showed that there was no significant difference between silybin A and B, indicating that they have similar pharmacokinetic behavior in rats. Conclusion: The method is simple, sensitive, stable and reliable, suitable for silybin, silymarin and its pharmacokinetics studies.