LC-MS/MS测定大鼠血浆中咖啡酸、绿原酸及其药代动力学研究

Study on determination of caffeic acid,chlorogenic acid in rat plasma and their pharmacokinetics with LC-MS /MS

该研究建立大鼠血浆中咖啡酸、绿原酸的LC-MS/MS测定方法,并用于大鼠体内的药代动力学研究。6只SD大鼠,单剂量静脉注射（4 mLkg-1）灯盏细辛注射液,以替硝唑为内标,用LC-MS/MS测定给药后血浆中的药物浓度,并用DAS 1.0软件计算药动学参数。咖啡酸、绿原酸的线性范围分别为2~128 μgL-1（r = 0.998 1）,3~384 μgL-1（r = 0.998 7）。方法学考察均符合要求。日内、日间变异系数（RSD）均小于10%,精密度和准确度等均符合生物样品分析的要求。大鼠体中咖啡酸药代动力学参数：t1/2β为（130.9138.77） min,AUC0-t为（4.890.96） mgminL-1,CL为（0.120.02） Lmin-1kg-1;绿原酸药代动力学参数：t1/2β为（49.388.85） min,AUC0-t为（9.540.95） mgminL-1,CL为（0.090.003） Lmin-1kg-1。该研究建立的LC-MS/MS分析方法准确灵敏,适于咖啡酸、绿原酸的药代动力学研究。

To establish a LC-MS/MS method to determine caffeic acid, chlorogenic acid in rat plasma and study their pharmacokinetics in rats. Six Sprague-Dawley rats were intravenously injected with 4 mLkg-1 of Dengzhanxixin injection, respectively. Their drug plasma concentration was determined by LC-MS/MS, with tinidazole as an internal standard. The pharmacokinetic parameters were calculated by DAS 1.0. The linear concentration ranges of caffeic acid, and chlorogenic acid were 2-128 μgL-1 （r=0.998 1） and 3-384 μgL-1 （r=0.998 7）, respectively. The methodological test showed conformance to the requirements. The intraday and inter-day variable coefficients were both less than 10.0%, indicating that both of legitimate precise and accuracy were in conformity with the requirements of biological sample analysis.For caffeic acid, the pharmacokinetic parameter t1/2β, AUC0-t, and CL were （130.9138.77） min, （4.890.96） mgminL-1 and （0.120.02） Lmin-1kg-1, respectively. For chlorogenic acid, the pharmacokinetic parameter t1/2β, AUC0-t and CL were （49.388.85） min, （9.540.95） mgminL-1 and （0.090.003） Lmin-1kg-1, respectively. The LC-MS/MS analysis method established in this study was proved to be so accurate and sensitive that it can be applied to the pharmacokinetic study of caffeic acid and chlorogenic acid.keywords：Dengzhanxixin injection