摘要
目的:建立LC-MS方法测定大鼠血浆中蒽醌成分含量,探讨5个大黄蒽醌成分(芦荟大黄素、大黄素、大黄酸、大黄酚、大黄素甲醚)三三配伍时在脑缺血大鼠模型中的药代动力学特征。方法:MCAO法制备大鼠局灶性脑缺血模型。模型大鼠随机分成11组,空白组1组,给药组10组。给药组将5个大黄蒽醌三三结合,给药剂量:芦荟大黄素(A)13.05 mg·kg^(-1),大黄素(B)34.65 mg·kg^(-1),大黄酸(C)17.25mg·kg^(-1),大黄酚(D)39.45 mg·kg^(-1),大黄素甲醚(E)26.4 mg·kg^(-1)。血浆样品经甲醇沉淀蛋白后,XBridge^(TM)C_(18)色谱柱分析,高分辨质谱检测。流动相为甲醇-3 mmol·L^(-1)乙酸铵,梯度洗脱。采用内标法测血药浓度,Kinetica 5.0药动学软件以非房室模型计算药代动力学参数。结果:当与不同的2个大黄蒽醌联用时,芦荟大黄素、大黄素、大黄酸、大黄酚和大黄素甲醚的药代动力学参数均存在差异。结论:本研究为这5个大黄蒽醌的作用机制研究提供理论基础,为其临床用药提供了实验参考。
Objective:To establish a LC-MS method to determine the content of 5 rhubarb anthraquinones in rat plasma and explore their pharmacokinetic characteristics in cerebral ischemia-reperfusion model rats when three kinds of the five anthraquinones were administrated in compatibility.Methods:A MCAO method was developed to establish focal cerebral ischemia rat model.The model rats were randomly divided into 11 groups,a blank group and the other 10 drug administration groups.In the drug administration group,three of five were compatibly administrated to treat rats with cerebral ischemia.Administration dose:aloe-emodin(A)13.05 mg·kg^(-1),emodin(B)34.65 mg·kg^(-1),rhein(C)17.25 mg·kg^(-1),chrysophanol(D)39.45 mg·kg^(-1),physcion(E)26.4 mg·kg^(-1).Plasma samples were precipitated with alcohol,analyzed on a XBridge^(TM)C_(18) column and detected using high-resolution mass spectrometry.The mobile phase was methanol-3 mmol·L^(-1) ammonium acetate with gradient elution.And the plasma concentration was measured by internal standard method,and Kinetica 5.0 pharmacokinetic software was applied to calculate the pharmacokinetic parameters with non-compartmental model.Results:When combined with two different rhubarb anthraquinones,the pharmacokinetic parameters of aloe-emodin,emodin,rhein,chrysophanol and physcion were all discrepant.Conclusion:This study provides a theoretical basis for the research on the mechanism of action of these five rhubarb anthraquinones,and provides an experimental reference for clinical medication.
作者
李荣荣
赵迪
冯素香
郝蕊
李焕茹
胡雁萍
刘学芳
LI Rong-rong;ZHAO Di;FENG Su-xiang;HAO Rui;LI H uan-ru;HU Yan-ping;LIU Xue-fang(Henan University of Chinese Medicine,Zhengzhou 450046,China;Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan&Education Ministry of P.R.,Zhengzhou 450046,China;Zhengzhou Key Laboratory of Chinese Medicine Quality Control and Evaluation,Zhengzhou 450046,China)
出处
《药物分析杂志》
CAS
CSCD
北大核心
2021年第3期427-435,共9页
Chinese Journal of Pharmaceutical Analysis
基金
河南省中医药大学博士基金科研项目(BSJJ-2016-01)。
关键词
液相质谱联用
大黄蒽醌
配伍
脑缺血大鼠模型
药代动力学特征
LC-MS
5 rhubarb anthraquinones
compatibility
cerebral ischemia-reperfusion model rats
pharmacokinetic characteristics
作者简介
通信作者:冯素香,Tel:13526403080,E-mail:fengsx221@163.com;第一作者:李荣荣,Tel:13838057402,E-mail:lirong_tg94@163.com。
