当归芍药散入血成分的分析及药代动力学研究(英文)

Identification and Determination of Absorbed Components of Danggui-Shaoyao-San in Rat Plasma

目的:研究大鼠口服给药当归芍药散后体内的入血成分及其药代动力学。方法:大鼠灌胃给予当归芍药散提取物后,以HPLC-DAD-MSn分析含药血清中药物成分,并建立主要入血成分的HPLC测定方法以应用于药代动力学研究。结果:大鼠灌胃给予当归芍药散提取物后血清中检测到7个原型成分和1个代谢产物,并对大鼠血浆中芍药内酯苷、芍药苷、阿魏酸和藁本内酯进行了测定。方法学考察了线性范围(0.025-5.60μg·ml-1)、定量限(0.022-0.18μg·ml-1)、日内和日间精密度(<10.1%)、准确度(92.5%-111.5%)和回收率(>80%)。结论:芍药苷硫酸酯、芍药内酯苷、芍药苷、阿魏酸、川芎内酯I、藁本内酯和丁烯基苯酞为当归芍药散主要的入血成分。对大鼠血浆中芍药内酯苷、芍药苷、阿魏酸和藁本内酯建立的测定方法简便、准确、灵敏度高,适用于血药浓度测定及其药动学研究。

AIM： To investigate the absorbed components of Danggui-Shaoyao-San （DSS） in raft plasma and their pharmacokinetics. METHODS： Serum samples from rats with DSS extract administrated orally were analyzed by HPLC-DAD-MSn and an HPLC-DAD method was established for the determination. RESULTS： Seven prototypes and one metabolite were identified in rat serum, and albiflorin, paeoniflorin, ferulic acid and ligustilide in rat plasma were determined for pharrnacokinetic study. The proposed method was validated with a linear range of 0.025-5.60μg·ml^-1 and limit of quantitation （LOQ） at 0.022-0.180μg·ml^-1, respectively. The RSD of intra- and inter-day precision variations were less than 10.1% and the accuracies ranged from 92.5%-111.5%. The overall recovery was over 80%. CONCLUSION： Paeoniflorin sulfonate, albiflorin, paeoniflorin, ferulic acid, senkyunolide I, ligustilide and butylidenephthalide were found to be the potentially effective constituents in DSS. The method for determination is simple and sensitive, which is proved to be suitable for pharmacokinetic study of albiflorin, paeoniflorin, ferulic acid and ligustilide in DSS.