杞荷分清饮中12种成分在正常及糖尿病模型大鼠体内药动学的比较研究

Comparison of in vivo pharmacokinetics of twelve constituents in Qihe Fenqing Yin in normal rats and diabetic rats

研究杞荷分清饮中12种活性成分(琥珀酸、新绿原酸、绿原酸、隐绿原酸、原儿茶醛、咖啡酸、5-O-阿魏酰奎宁酸、对香豆酸、荷叶碱、槲皮素、齐墩果酸、熊果酸)在正常和糖尿病模型大鼠体内的药动学差异。采用高脂饲料喂养联合腹腔注射链脲佐菌素建立糖尿病大鼠模型,建立超高效液相色谱-三重四极杆-线性离子阱质谱(UHPLC-QTRAP-MS/MS)方法,同时测定正常大鼠和模型大鼠分别单次灌胃给予杞荷分清饮后血浆中12种成分的含量。结果显示,所建立的分析方法对12种所测定成分线性关系良好,专属性、准确度、精密度、稳定性等方法学均符合要求。采用DAS 3.2.8软件拟合计算药动学参数结果表明,模型组中除咖啡酸、5-O-阿魏酰奎宁酸、齐墩果酸外其余9种成分半衰期时间(t1/2)相对正常组延长;隐绿原酸、对香豆酸、熊果酸、齐墩果酸药时曲线下面积(AUC0-t)模型组相对正常组增加,且平均驻留时间(MRT)延迟;正常组中槲皮素、荷叶碱出现“双峰”现象,模型组未见,提示疾病状态下药物的药动学参数出现明显差异。

This paper aims to study the pharmacokinetic differences of twelve effective constituents(succinic acid,neochlorogenic acid,chlorogenic acid,cryptochlorogenic acid,protocatechuic aldehyde,caffeic acid,5-O-ferulogeninic acid,p-coumaric acid,nuciferine,quercetin,oleanolic acid,and ursolic acid)in Qihe Fenqing Yin in normal and diabetic rats.The diabetic rat model was established by a high-fat diet combined with intraperitoneal injection of streptozocin.A UHPLC-QTRAP-MS/MS method was established for the simultaneous determination of 12 constituents in the plasma of normal rats and model rats after a single intragastric administration of Qihe Fenqing Yin.The results show that the established analytical method has a good linear relationship with the 12 components,and the specificity,accuracy,precision,and stability meet the requirements.The computational pharmacokinetic parameters are fitted by DAS 3.2.8 software,and the results show that the half-life time(t1/2)of the other nine components in the model group was longer than that in the normal group except for caffeic acid,5-O-ferulogeninic acid,and oleanolic acid.The area under curve(AUC0-t)of cryptochlorogenic acid,p-coumaric acid,ursolic acid,and oleanolic acid increases compared with the normal group.Meanwhile,mean residence time(MRT)delays.The"double peaks"of quercetin and nuciferine in the normal group are not observed in the model group,suggesting that the pharmacokinetic parameters of the drugs in the disease state are significantly different.