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目的:研究葛根芩连汤中各味药材的主要成分葛根素、黄芩苷、小檗碱与甘草酸联合给药后在大鼠体内的代谢产物化学结构。方法:健康大鼠灌胃给药,收集0～24 h的尿样,尿样经C18固相小柱分离纯化后,经UPLC-Q-TOF-MS分析鉴定其中的代谢产物。代谢物的结构鉴定主要依据各代谢物与对照品的一级质谱电离规律、裂解规律间的关联性和相关文献的数据。结果:灌胃给药(葛根素、小檗碱、黄芩苷和甘草酸)后,在大鼠尿液中鉴定了16个代谢产物的化学结构,其中6个来自葛根素,分别为葛根素、大豆苷、大豆苷元、二氢大豆苷元、葛根素硫酸酯结合产物和葛根素葡萄糖醛酸结合产物;2个来自黄芩苷,分别为baicalin-6-O-β-glucose-7-O-β-glucopyranuronoside,baicalin-6-O-β-glucopyranuronoside-7-O-β-glucopyranuronoside;8个来自小檗碱,分别为thalifendine,berberrubine,demethyleneberberine,jatrorrhizine,demethyleneberberine葡萄糖醛酸结合物,jatrorrhizine葡萄糖醛酸结合物,berberrubine-9-O-β-D-glucuronide,demethyleneberberine-2,3-O-β-D-glucuronide。结论:主要成分联合给药后,代谢产物主要以苷元或以葡萄糖苷、葡萄糖醛酸结合物为主,也有以原型排出;甘草酸生物利用度低,有明显的首过效应,且经尿液排泄量极少,未检出代谢产物。
OBJECTIVE: To study the chemical structure of metabolites in Puerarin, baicalin, berberine and glycyrrhizin, the main components of Gegen Qinlian Decoction. Methods: The healthy rats were intragastrically administrated and the urine sample was collected for 0-24 h. The urine samples were separated and purified by C18 solid phase column. The metabolites were identified by UPLC-Q-TOF-MS. The structure identification of metabolites is mainly based on the first-order mass spectrometry ionization laws of each metabolite and the reference substance, the correlation between the cracking laws and the data of related literatures. Results: The chemical structures of 16 metabolites were identified in rat urine after intragastric administration (puerarin, berberine, baicalin and glycyrrhizic acid), of which 6 were from puerarin, puerarin, Daidzein, daidzein, dihydrodaidzein, puerarin sulfate binding products and puerarin glucuronic acid binding products; two from baicalin, baicalin-6-O-β-glucose-7-O- β-glucopyranuronoside, baicalin-6-O-β-glucopyranuronoside-7-O-β-glucopyranuronoside; 8 from berberine respectively thalifendine, berberrubine, demethyleneberberine, jatrorrhizine, demethyleneberberine glucuronic acid conjugate, jatrorrhizine glucuronic acid Conjugate, berberrubine-9-O-β-D-glucuronide, demethyleneberberine-2,3-O-β-D-glucuronide. Conclusion: After the combination of the main components, the main metabolites are mainly aglycone or glucoside and glucuronic acid conjugates, which are also excreted as prototypes. The bioavailability of glycyrrhizin is low and has obvious first pass effect. Very little fluid excretion, no detectable metabolites.