采用超高效液相色谱-串联质谱(UHPLC-MS/MS)技术同时测定正常大鼠和糖尿病模型大鼠血浆中补骨脂素、异补骨脂素、补骨脂酚、补骨脂查尔酮、补骨脂二氢黄酮甲醚、补骨脂宁、补骨脂甲素、补骨脂乙素、新补骨脂异黄酮、巴库查尔酮及corylifol A 11种有效成分，以阐明补骨脂香豆素类、黄酮类及单萜酚类在正常和糖尿病模型大鼠体内的药代动力学特征。以高糖高脂饲料结合每2d注射一次1％链脲佐菌素诱导2型糖尿病(T2DM)大鼠模型，灌胃给予补骨脂后采集不同时间点血浆，血浆样品经乙酸乙酯沉淀蛋白，以UHPLC-MS/MS测定血浆中补骨脂11种成分的血药浓度，采用DAS 3。0软件计算药动学参数。结果显示，雌、雄性T2DM大鼠灌胃给予补骨脂，补骨脂素、异补骨脂素、补骨脂酚、补骨脂二氢黄酮甲醚等8种受试成分的药动学行为与正常大鼠存在显著性差异。其中香豆素类成分补骨脂素、异补骨脂素、补骨脂宁在雌性与雄性T2DM大鼠体内均出现入血暴露水平降低，但黄酮类成分如补骨脂二氢黄酮甲醚、corylifol A、巴库查尔酮以及单萜酚类成分补骨脂酚在雌性T2DM大鼠体内的暴露减少，而在雄性患病大鼠体内暴露增多，提示补骨脂在临床用药时针对不同性别患者应合理调整服用剂量。
Pharmacokinetics of 11 active components of Psoraleae Fructus in normal and diabetic rats
A total of 11 active ingredients including psoralen,isopsoralen,bakuchiol,bavachalcone,bavachinin,corylin,coryfo-lin,isobavachalcone,neobavaisoflavone,bakuchalcone,and corylifol A from Psoraleae Fructus in the plasma samples of diabetic and normal rats were simultaneously determined by UHPLC-MS/MS.The pharmacokinetic parameters were calculated to elucidate the phar-macokinetic profiles of coumarins,flavonoids,and monoterpene phenols in normal and diabetic rats.The rat model of type 2 diabetes mellitus(T2DM)was induced by a high-sugar and high-fat diet combined with injection of 1％streptozotocin every two days.The plas-ma samples were collected at different time points after the rats were administrated with Psoraleae Fructus.The proteins in the plasma samples were precipitated by ethyl acetate,and the plasma concentrations of the 11 components of Psoraleae Fructus were determined by UHPLC-MS/MS.The pharmacokinetic parameters were calculated by DAS 3.0.The results showed that the pharmacokinetic beha-viors of 8 components including psoralen,isopsoralen,bakuchiol,and bavachinin from Psoraleae Fructus in both female and male mo-del rats were significantly different from those in normal rats.Among them,the coumarins including psoralen,isopsoralen,and corylin showed lowered levels in the blood of both female and male model rats.The flavonoids(bavachinin,corylifol A,and bakuchalcone)and the monoterpene phenol bakuchiol showed decreased levels in the female model rats but elevated levels in the male model rats.It is suggested that the dosage of Psoraleae Fructus should be reasonably adjusted for the patients of different genders at the time of clini-cal administration.
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