Résumé
ObjectiveTo evaluate the metabolic stability of lucidin by incubating liver microsomes and liver S9 from 4 species， and to compare the species differences in metabolism of lucidin in vitro. MethodA qualitative and quantitative method of lucidin based on ultra-high performance liquid chromatography-high resolution mass spectrometry （UHPLC-HRMS） was established and verified. Lucidin was incubated with rat， mouse， beagle dog， human liver microsomes and liver S9 to investigate the metabolic stability parameters， metabolites， metabolic pathways. ResultHepatic clearance （CLh） of lucidin was in order of mouse>rat>beagle dog>human in both phase Ⅰ and phase Ⅱ incubation system. Its metabolic stability was good in rat， beagle dog and human， while it showed metabolic instability and moderate metabolic stability in mouse microsomes and liver S9， respectively. A total of 5 metabolites were rapidly identified， including 3 oxidation metabolites of phase Ⅰ and 2 sulfation metabolites of phase Ⅱ. The production rate of metabolites was consistent with the results of metabolic stability. ConclusionThe established UHPLC-HRMS is simple and specific， which can be used for the study on the metabolic stability and metabolites of lucidin. Its metabolic stability and metabolite production rate in vitro are significantly different among species， the metabolic characteristics of rat and beagle dog are similar to human， which provides an important reference for subsequent research in vivo， safety evaluation and animal model selection of lucidin.