积雪草酸大鼠体内药动学考察

Study on Pharmacokinetics of Asiatic Acid in Rats

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0.1~20μg.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：tmax=2.0 min,Cmax=14.7μg.mL-1,t1/2=35.1 min,AUC0-t=217.0μg.min.mL 1,AUC0∞=234.3μg.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。

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 10mg·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·m L-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： tmax=2.0min,Cmax=14.7 μg·m L-1,t1/2=35.1min,AUC0-t=217.0 μg·min·m L-1,AUC0-∞=234.3 μg·min·m L-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.