RESUMO
Guizhi Fuling capsule (GZFL), a traditional Chinese medicine formulation, is widely used in China to relieve pain from dysmenorrhea and is now in a Phase II clinical trial in the USA. Due to the low exposure of the five main medicative ingredients (amygdalin, cinnamic acid, gallic acid, paeoniflorin and paeonol) of GZFL in human, a strategy was built to qualitatively and quantitatively identify the possible metabolites of GZFL and to describe the pharmacokinetic profiles of GZFL in human. In this strategy, LC-Q-TOF/MS was used to identify and structurally elucidate the possible metabolites of GZFL in vivo; and a time-based metabolite-confirming step (TBMCs) was used to confirm uncertain metabolites. The simultaneously quantitation results by LC-MS/MS showed low exposure of the five medicative ingredients. According to the strategy we built, a total of 36 metabolites were found and structurally elucidated. The simultaneously semi-quantitative analysis by LC-MS/MS showed that obvious time-concentration curves could be established for 12 of the metabolites, and most of them showed a relatively higher exposure. This study provides a better understanding of the metabolic processes of GZFL in human.
Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Acetofenonas/administração & dosagem , Acetofenonas/química , Acetofenonas/farmacocinética , Amigdalina/administração & dosagem , Amigdalina/química , Amigdalina/farmacocinética , Cápsulas , Cromatografia Líquida de Alta Pressão/métodos , Cinamatos/administração & dosagem , Cinamatos/química , Cinamatos/farmacocinética , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Feminino , Ácido Gálico/administração & dosagem , Ácido Gálico/química , Ácido Gálico/farmacocinética , Glucosídeos/administração & dosagem , Glucosídeos/química , Glucosídeos/farmacocinética , Voluntários Saudáveis , Humanos , Masculino , Estrutura Molecular , Monoterpenos/administração & dosagem , Monoterpenos/química , Monoterpenos/farmacocinética , Espectrometria de Massas em Tandem/métodosRESUMO
Drug metabolism studies, including in vivo and in vitro metabolism studies, are significant in the design of candidate compounds and screening of lead compounds at drug discovery/development stages. Compared with in vivo metabolism studies, in vitro metabolism studies have the advantages of rapidity, simplicity, without consumption of large amounts of samples and animals. Moreover, it is convenient for researchers to observe the selective interaction between compound and target. Therefore, in vitro metabolism studies are appropriate for high throughput screening of compounds which are lack of metabolism information and have been widely used during drug discovery stages. This article briefly introduced the application of in vitro drug metabolism studies based on the metabolic stability, reaction phenotyping and metabolic drug-drug interactions, aiming to raise valuable evaluation strategies for innovative drug discovery in China.