In vitro Identification of Spinosin Metabolites in Human Liver Microsomes Using a Simple and Sensitive UHPLC-Q-TOF-MS/MS Method

Abstract

Background: Spinosin is one of the major bioactive constituents among the total flavonoids in semen ziziphi spinosae, which has sedation and hypnosis actions. Methods: A simple and rapid high-resolution ultra-high-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) method was developed and validated for predicting the structures of its spinosin metabolic products. This paper presents the first research focused on the metabolites of spinosin in human liver microsomes. Results: Based on the analytical strategy, 8 spinosin metabolites were detected in human liver microsome incubation samples, and the metabolic pathways required to generate these metabolites were proposed. However, no phase II metabolites were found. The cytochrome P450 enzyme is the main metabolic enzyme involved in drug metabolism, accounting for approximately 75% of the total number of different metabolic reactions. Conclusion: The in vitro metabolism of spinosin was proposed. These results allow us to learn about spinosin metabolism, leading to a better understanding of drug biotransformation and providing a basis for clinical applications. Moreover, this study laid the foundation for developing new pharmaceutical drugs.