[关键词]
[摘要]
目的 基于中药质量标志物(Q-marker)概念,研究肉桂、栀子及两者配伍后的复方桂栀助眠方中主要成分在食蟹猴体内的药动学变化,为桂栀助眠方的Q-marker确定提供科学依据。方法 建立UPLC-MS/MS方法,对桂栀助眠方配伍前后7个主要成分肉桂酸、4-甲氧基肉桂酸、香豆素、栀子苷、京尼平、京尼平苷酸、绿原酸在食蟹猴中的药动学行为进行比较研究。结果 与肉桂、栀子单味药组相比,桂栀助眠方组食蟹猴血浆中肉桂酸、香豆素、京尼平苷酸、绿原酸的药时曲线下面积(AUC)、达峰浓度(Cmax)均显著增加;肉桂酸、4-甲氧基肉桂酸、香豆素消除半衰期(t1/2)明显降低;4-甲氧基肉桂酸、栀子苷的血药浓度达峰时间(tmax)延长。结论 配伍后桂栀助眠方能够显著改变复方中主要成分的体内暴露状态,7个主要成分可作为桂栀助眠方的Q-markers。
[Key word]
[Abstract]
Objective To study the effect of compatibility on pharmacokinetics of the main components of Guizhi Zhumian prescription (GZP) based on the concept of Q-marker and to provide evidences for the determination of the Q-markers of this prescription. Methods UPLC-MS/MS method was established for the study of the pharmacokinetics behaviors of seven main components, including cinnamic acid, 4-methoxycinnamic acid, coumarin, gardenoside, genipin, geniposidic acid, and chlorogenic acid, before and after the compatibility of GZP in plasma of cynomolgus monkeys. Results Compared with the pharmacokinetics parameters of Cinnamomum cassia and Gardenia jasminoides, the AUC and Cmax of cinnamic acid, coumarin, geniposidic acid, and chlorogenic acid in GZP were increased obviously; The t1/2 of cinnamic acid, 4-methoxycinnamic acid, and coumarin were decreased; And the tmax of 4-methoxycinnamic acid, and geniposide were prolonged. Conclusion Compatibility of GZP could significantly change the in vivo exposure status of the main components, and the seven main compounds were determined to be the Q-markers of GZP.
[中图分类号]
R285.5
[基金项目]
2017年广西中医药大学引进博士科研启动基金项目(2017BS044);2017年广西壮族自治区瑶药材质量标准项目(第二卷)——黄红钻(17-259-20);钻类瑶药抗肿瘤活性筛选与应用技术研究(桂科AB17195019);广西科技计划项目(AB17195O19);广西科技计划项目(AD17129010);广西科技计划项目(17-259-20);广西科技计划项目(AD17195025)