积雪草酸大鼠体内药动学考察

Study on Pharmacokinetics of Asiatic Acid in Rats

关键词:  积雪草酸  血药浓度  固相萃取  一室模型

Key words:  asiatic acid  plasma concentration  solid phase extraction  one compartment model

摘要:

目的 建立大鼠血浆中积雪草酸(asiatic acid，AA)的柱前衍生化HPLC，探讨AA在大鼠体内的药动学。方法 SD大鼠，♂，尾静脉注射AA(10 mg?kg^-1)，于给药后不同时间采取血浆，经DIKMA Proelut PLS柱固相萃取，柱前衍生化HPLC测定血浆中AA浓度(以甘草次酸为内标)，药物统计软件(PKS 1.0)拟合统计药动学参数。结果 血药浓度在0.1~20 μg?mL^-1内线性良好(r=0.999 6)，平均提取回收率为71.1~79.9%，日内、日间精密度RSD均<13%，样品在?20 ℃放置，经2次冻融循环后基本稳定。AA在大鼠体内药-时曲线符合一室开放模型，主要药动学参数为：t_max=2.0 min，C_max=14.7 μg?mL^-1，t_1/2=35.1 min，AUC_0-t=217.0 μg?min?mL^-1，AUC_0-∞=234.3 μg?min?mL^-1。结论 AA在大鼠体内消除迅速，所建立的提取及柱前衍生化HPLC适用于体内AA的测定。

Abstract:

OBJECTIVE To establish a sensitive precolumn derivatization HPLC method for determination of plasma concentration of asiatic acid(AA) and evaluate its pharmacokinetics characteristics in rats. METHODS The male SD rats were intravenously administrated AA by 10 mg?kg^-1. The plasma samples were taken at different times, concentrated by SPE method and determined by precolumn derivatization RP-HPLC method, the glycyrrhetinic acid was used as an internal standard. The pharmaeokinetie parameters were accessed by PKS 1.0. RESULTS Excellent liner relationship was obtained in the range of 0.1 to 20 μg?mL^-1(r=0.999 6). The averang extraction recovery was 71.1%?79.9%. The intra- and inter-day RSDs were less than 13%. The samples were stabled at -20 ℃, and remained stable after twice freeze-thaw cycles. AA was fitted to a one compartment open model in rats, mainly pharmacokinetic parameters as follow: t_max=2.0 min, C_max=14.7 μg?mL^-1, t_1/2=35.1 min, AUC_0-t=217.0 μg?min?mL^-1, AUC_0-∞=234.3 μg?min?mL^-1. CONCLUSION AA is disposed extensively and rapidly in rats. The method can be used to determine the concentration and to investigate the pharmacokinetics of AA in rats.