摘要
目的:研究真武汤在大鼠体内的入血成分及其代谢物,并对4种入血成分进行药动学研究。方法:采用超高效液相色谱-四极杆/静电场轨道阱高分辨质谱(UPLC-Q-Orbitrap HRMS)技术结合Compound Discover 3.0软件,通过对比真武汤样品、空白血浆、给药血浆色图谱,鉴定并推测真武汤在大鼠血浆中的原型化合物及代谢物。在此基础上,对苯甲酰新乌头原碱、白术内酯Ⅲ、芍药苷、6-姜酚进行药动学研究。结果:共鉴定了24种原型化合物和18种代谢物,主要代谢途径为氧化、还原、水解、去甲基、去亚甲基、去苯甲酰基、葡萄糖醛酸化等。药动学结果显示,4种成分的C_(max)在131.7~351.1 ng·mL^(-1),t_(max)在0.53~1.58 h,t_(1/2)在4.82~7.24 h,AUC_(0~24)在804.1~1980.7 ng·h·mL^(-1),AUC_(0~∞)在882.7~2108.8 ng·h·mL^(-1),MRT_(0~24)在5.47~6.89 h,MRT_(0~∞)在6.58~9.36 h。结论:分析了真武汤的入血成分并进行药动学研究,对真武汤体内药效物质基础及其临床应用研究提供实验依据。
OBJECTIVE To study the absorbed components and metabolites of Zhenwu Decoction in rat plasma,and to study the pharmacokinetics of the four absorbed components.METHODS Ultra-high performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry(UPLC-Q-Orbitrap HRMS)technology combined with Compound Discover 3.0 software was used to identify and speculate the prototype compounds and metabolites of Zhenwu Decoction in rat plasma by comparing the chromatograms of Zhenwu Decoction samples,blank plasma and administration plasma.On this basis,the pharmacokinetics of benzoylneaconitine,atractylideⅢ,paeoniflorin and 6-gingerol were studied.RESULTS A total of 24 prototype compounds and 18 metabolites were identified.The main metabolic pathways were oxidation,reduction,hydrolysis,demethylation,demethylene,debenzoyl,and glucuronidation.The results of pharmacokinetic parameters showed that the C_(max)of the four components was 131.7-351.1 ng·mL^(-1),t_(max)was 0.53-1.58 h,t_(1/2)was 4.82-7.24 h,AUC_(0~24)was 804.1-1980.7 ng·h·mL^(-1),AUC_(0~∞)was at 882.7-2108.8 ng·h·mL^(-1),MRT_(0~24)at 5.47-6.89 h,MRT_(0~∞)at 6.58-9.36 h.CONCLUSION The absorbed components of Zhenwu Decoction in plasma were analyzed and the conducts pharmacokinetic research were studied,which could provide experimental basis for the research on the pharmacodynamic material basis of Zhen-wu-tang decoction and its clinical application.
作者
田萍
安鸿志
位恒超
张薇
王世冉
梁瑞峰
古耘
马开
韩德恩
TIAN Ping;AN Hongzhi;WEI Hengchao;ZHANG Wei;WANG Shiran;LIANG Ruifeng;GU Yun;MA Kai;HAN Deen(Institute of Chinese Medicine,Henan Integrative Medicine Hospital/Henan Academy of Chinese Medicine,Henan Zhengzhou 450004,China;College of Pharmacy,Henan University of Chinese Medicine,Henan Zhengzhou 450046,China;Henan Research Center for Special Processing Technology of Chinese Medicine,Henan Zhengzhou 450046,China)
出处
《中国医院药学杂志》
CAS
北大核心
2023年第22期2478-2483,共6页
Chinese Journal of Hospital Pharmacy
基金
国家自然科学基金资助项目(编号:81473368)
河南省中医药科学研究专项课题(编号:2017ZY2036)
河南省中医药研究院基本科研业务费课题(编号:2004826)。