Identification and characterization of the absorbed components and metabolites of Gandouling tablets in rats' plasma, liver, and urine by UPLC-Q-TOF-MS.

Gandouling (GDL), a famous proprietary Chinese medicine, has been utilized in China's clinics for decades to treat Wilson's disease. However, its metabolism in vivo needs to be clarified. In this study, Ultra Performance Liquid Chromatography-quadrupole time-of-flight mass spectrometry-tandem (UPLC-Q-TOF-MS) was employed to analyze the metabolic pathways of these critical components in the rat after identifying the prototypes and metabolites of GDL in the plasma, liver, and urine of both normal and copper-loaded rats. As a result, 49 components were detected in the plasma of normally administered rats, including 29 prototype compounds and 20 metabolites; and 26 components were detected in the liver of normally administered rats, including 16 prototype compounds and 10 metabolites. 43 components were detected in the plasma of copper-laden administered rats, including 25 prototype compounds and 18 metabolites; and 23 components were detected in the liver of copper-laden administered rats, including 15 prototype compounds and 8 metabolites. A total of 73 GDL-related substances were detected in the urine of rats. The study results showed that the compositions in rats' plasma, liver, and urine were similar, mainly alkaloids and anthraquinones. The alkaloid components are mainly metabolized by phase I metabolism in vivo and the metabolic pathways are methylation, demethylation, etc. The anthraquinone components are mainly metabolized by phase II metabolism in vivo, and the metabolism modes are mainly glucuronidation and sulfation. The present study comprehensively analyses the metabolic properties of GDL and sets an essential basis for further investigations on the pharmacokinetics, in vivo bioactive components, and mechanism of action of GDL.