丹酚酸B及二甲酯在人肝微粒体中代谢稳定性研究及代谢产物鉴定  

Metabolic stability of salvianolic acid B and dimethyl lithospermate B in human liver microsomes and metabolite identification

作　　者：袁春平[1,2] 侯惠民[1] 曾杉[2] 

机构地区：[1]中国医药工业研究总院药物制剂国家工程研究中心,上海201203 [2]国药集团广东环球制药有限公司,佛山528305

出　　处：《中国新药杂志》2016年第13期1543-1549,共7页Chinese Journal of New Drugs

摘　　要：目的:对比丹酚酸B(SAB)和丹酚酸B二甲酯(DMB)在人肝微粒体中的代谢稳定性,并鉴定DMB的代谢产物。方法:应用体外人肝微粒体孵育体系,采用HPLC-MS/MS法测定两者的剩余浓度,考察SAB和DMB的代谢稳定性,并鉴定代谢产物。结果:SAB在人肝微粒体孵育中不代谢;DMB在人肝微粒体和空白孵育液中各得到了4个代谢产物,其中有2个产物相同。结论:SAB在人肝微粒体中稳定;DMB在人肝微粒体和空白孵育液中均不稳定,且人肝微粒体中的代谢速率比空白孵育液快,代谢主要途径为酯键水解。Objective： To study the metabolic stability of salvianolic acid B（ SAB） and dimethyl lithospermate B（ DMB） in human liver microsomes（ HLM） and identify the metabolites of DMB. Methods： A liquid chromatography-tandem mass spectrometry（ LC-MS / MS） method was used to determine the remaining concentrations and identify the metabolites of SAB and DMB in HLM. Results： SAB didn＇t show any trend of metabolism during incubation with HLM and NADPH reaction system,but DMB showed significant decline when incubating with HLM. The metabolic trends of DMB were similar in the presence of or without NADPH. Four metabolites were detected both in HLM and blank incubation with DMB,and two metabolites were the same.Conclusion： SAB is stable both in HLM and blank incubation medium,but DMB is on the contrary. The metabolic rate of DMB is faster in HLM than in blank incubation medium,with estelysis as the main metabolic way.

关 键 词：丹酚酸B 丹酚酸B二甲酯 人肝微粒体 代谢稳定性 产物鉴定 

分 类 号：R286.2[医药卫生—中药学]