Gandou Decoction (GDD), a well-known traditional Chinese medicine prescription, has been widely used for decades in clinical practice to treat Wilson's disease (WD) in China. However, due to lack of in vivo metabolism research, the absorbed components and metabolites of GDD have not been fully elucidated. In this study, a rapid and high-throughput ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MSE) was applied to rapidly identify prototypes and metabolites after oral administration of GDD. On this basis, the possible metabolic pathways of the main prototypes were proposed between normal and copper-laden rats. As a result, a total of 89 GDD-related xenobiotics were detected in normal dosed rats, including 83 (36 prototypes and 47 metabolites) in plasma and 52 (21 prototypes and 31 metabolites) in liver; a total of 77 GDD-related xenobiotics were detected in copper-laden dosed rats, including 68 (31 prototypes and 37 metabolites) in plasma and 42 (19 prototypes and 23 metabolites) in liver. Our findings showed that anthraquinones, alkaloids and protostane triterpenoids as well as a few saponins, flavonoids, tannins and curcuminoids were the main absorbed chemical components of GDD in rat plasma; anthraquinones, protostane triterpenoids and curcuminoids were the major components in rat liver. Glucuronidation and sulfation were deduced to be the predominant metabolic pathways of GDD. Methylation, acetylation, reduction, hydroxylation, demethylation and deglycosylation were often occurred in the metabolic process. Furthermore, the holistic metabolic profile of GDD revealed that copper-laden rats and normal rats had certain differences in drug absorption and metabolism. This study offered a solid basis for ascertaining bioactive components and action mechanism of GDD.
Keywords: Copper-laden model; Gandou decoction; Metabolic profiling; UPLC-Q-TOF-MS(E).
Copyright © 2019 Elsevier B.V. All rights reserved.