目的 考察大鼠ig芎汤超临界提取部位后,其有效成分藁本内酯、洋川芎内酯A、正丁基苯酞在大鼠体内的药动学规律。方法 将芎汤超临界提取部位SD大鼠ig给药后,采集不同时间点的大鼠血浆样品,采用高效液相色谱法测定其中藁本内酯、洋川芎内酯A、正丁基苯酞的血药浓度,并采用PKSolver 2.0药动学软件计算其药动学参数,建立其药物代谢曲线。结果 藁本内酯、洋川芎内酯A、正丁基苯酞分别在0.416～16.640、0.40～16.05、0.52～31.50 μg/mL线性关系良好,回收率均大于84%,日内、日间精密度RSD均小于5%。藁本内酯主要药动学参数:t_1/2为(2.082 0±0.637 6)h、C_max为(3.272 5±0.955 5)μg/mL、AUC_0~t为(15.400±1.812)μg·h/mL;洋川芎内酯A和正丁基苯酞的药动学参数与藁本内酯基本相似。结论 建立的芎汤3种有效成分在大鼠血浆中的HPLC测定方法专属性强、灵敏度高,可用于大鼠血浆中藁本内酯、洋川芎内酯A、正丁基苯酞血药浓度的测定及药动学研究。

Objective To investigate the pharmacokinetics of ligustilide, senkyunolide A, and butylphthalide in supercritical CO₂ extraction (SFE) fraction of Xiongqiong Decoction after ig administration in rats. Methods Plasma samples were collected according to different time periods after ig administration, and the concentration of ligustilide, senkyunolide A, and butylphthalide in plasma samples was determined by HPLC so as to calculate the pharmacokinetic parameters and establish the metabolism curves by PKSolver 2.0 pharmacokinetic software. Results Excellent liner relationship of ligustilide, senkyunolide A, and butylphthalide was obtained in the range of 0.416—16.640 μg/mL, 0.40—16.05 μg/mL, and 0.52—31.50 μg/mL, respectively. The recovery of the method was more than 84%, and the intra- and inter-day RSD values were less than 5%. The pharmacokinetics parameters of ligustilide were as follows: t_1/2 (2.082 0 ± 0.637 6) h, C_max (3.272 5 ± 0.955 5) μg/mL, AUC_0-t (15.400 ± 1.812) μg·h/mL, and the pharmacokinetics parameters of senkyunolide A and butylphthalide were similar to those of ligustilide. Conclusion The method for the determination of three effective components from Xiongqiong Decoction in plasma samples is precise, specific, and suitable for the pharmacokinetic study and determination of the three effective components simultaneously.

山东省自然科学基金项目(ZR2009CM055)