野黄芩素及其葡萄糖醛酸结合物在大鼠体内的药动学研究  

Pharmacokinetic studies of scutellarein and glucuronide scutellarin in rats

作　　者：刘跃[1] 黄勇[1] 董永喜[2] 王永林[1] 郑林[1] 

机构地区：[1]贵阳医学院药学院贵州省药物制剂重点实验室,贵州贵阳550004 [2]贵阳医学院民族药与中药开发应用教育部工程研究中心,贵州贵阳550004

出　　处：《中国药理学通报》2014年第5期711-715,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81060359);贵州省中药现代化科技产业专项项目(No黔科合中药字[2011]5029号);贵州省教育厅省长基金资助项目(No黔省专合字[2011]50号);贵州省中药现代化[No黔科合中药字(2011)5081号]

摘　　要：目的建立测定大鼠血浆中野黄芩素及其代谢产物葡萄糖醛酸结合物浓度的UPLC-MS／MS法，并讨论两者在大鼠体内的药代动力学过程。方法色谱采用Waters BEH C18色谱柱，流动相为0．1％甲酸乙腈-0．1％甲酸水溶液，梯度洗脱，质谱采用多反应监测（MRM）进行正离子检测野黄芩素。大鼠静脉给予野黄芩素，测定给药后不同时间的野黄芩素的血药浓度；采用酶解方式间接测定野黄芩素葡萄糖醛酸结合物的血药浓度，以DAS2．0软件获得药动学参数。结果野黄芩素在0．116—28．2mg·L-1呈良好线性相关，提取回收率为80．5％～90．0％，精密度、准确度、稳定性良好。药代动力学研究结果表明静脉给予野黄芩素后其原型及其葡萄糖醛酸结合物药代动力学过程均符合二室模型。结论本研究所建立的方法具有灵敏度高，重现性好，操作简便等特点，可用于同时测定野黄芩素及其葡萄糖醛酸结合物在体内的浓度，便于原型药物及其代谢物产物的药动学研究。Aims To establish a UPLC-MS/MS method for the determination of plasma concentration of scutellarein and its metabolite and to study their pharmacokinetics in rat plasma. Methods The analysis was achieved by BEH C18 column with a mobile phase composed of 0. 1% formic acid in acetonitrile and 0.1 % aqueous formic acid using step gradient elution. A TQD tandem mass spectrometry equipped with electrospray ionization source was used as detector and operated by multiple reaction monitoring（MRM） positive ion mode. After intravenous injection of scutellarein, the concentrations of scutellarein and its major metabolite glucuronide seutellarin in rat plasma were determined at different time points. The pharmacokinetic parameters were calculated by DAS 2.0 software. Results Good linearity was achieved for scutellarein, the extraction recovery was between 80.5 % to 90.5 %, the precisions and accuracy were good. The result showed the pharmacokinetic profiles of scutellarein and glucuronide scutellarin both fit to the two-compartment model. Conclusion The above mentioned method is specific, rapid, sensitive and suitable for the pharmacokinetic studies of scutellarein and its metabolite.

关 键 词：野黄芩素 野黄芩素葡萄糖醛酸结合物 大鼠 血药浓度 UPLC—MS MS 药动学 

分 类 号：R-332[医药卫生] R282.71