雷公藤甲素温敏凝胶在大鼠体内的药代动力学研究

Research on pharmacokinetic of triptolide thermosensitive gel for rats

建立LC-MS测定雷公藤甲素(TP)在大鼠体内血药浓度方法,并计算药代动力学参数。采用Agilent ZORBAX SB-C18(2.1 mm×50 mm,1.8μm)色谱柱;流动相为甲醇(A)-水溶液(B)梯度洗脱;流量为0.3 mL/min;柱温35℃;进样量5μL;多反应监测(MRM),离子化方式为负模式。SPF级SD大鼠18只,分为空白、温敏凝胶和溶液组,采用单剂量关节腔注射给药。给药后大鼠尾部静脉取血,LC-MS测定各时间点血浆药物浓度,DAS3.0计算药代动力学参数。在0.1~2.0μg/L浓度范围内,TP与内标阿魏酸峰面积比值与浓度的线性关系良好。温敏凝胶和溶液组主要药动力学参数t1/2、Tmax和AUC分别为:27.506 h、0.75 h、3.972μg/L·h和16.967 h、0.5 h、2.283μg/L·h。该方法可用于TP关节腔注射给药在大鼠体内药代动力学研究,为TP温敏凝胶制剂开发提供理论依据。

This paper established a LC-MS method for determining the plasma concentration of triptolide(TP)in rats and to calculate pharmacokinetic parameters.An Agilent ZORBAX SB-C18(2.1 mm×50 mm,1.8μm)chromatographic column was used;the mobile phase was methanol(A)-aqueous solution(B)gradient elution;the flow rate was 0.3 mL/min;the column temperature was 35℃;the injection volume 5μL;Multiple Reaction Monitoring(MRM),ionization mode was negative mode.18 SPF grade SD rats were divided into blank,temperature-sensitive gel and solution groups,and were administered by single-dose intra-articular injection.After administration,blood was collected from the tail vein of rats,and the plasma drug concentration was determined by LC-MS at each time point.DAS3.0 was used to calculate the pharmacokinetic parameters.Within the concentration range of 0.1-2.0μg/L,the linear relationship between the ratio of TP and internal standard ferulic acid peak area and concentration was good.The main pharmacokinetic parameters t1/2,Tmax and AUC of the temperature-sensitive gel and solution groups were:27.506 h,0.75 h,3.972μg/L·h and 16.967 h,0.5 h,2.283μg/L·h.This method can be used to study the pharmacokinetics of TP articular injection in rats,and provided a theoretical basis for the development of TP temperature-sensitive gel formulations.