Characterization of the Metabolic Profile of Evodiamine in Human Liver Microsomes and Hepatocytes by UHPLC-Q Exactive Mass Spectrometer.

Evodiamine is an indoloquinazoline alkaloid isolated from the fruit of , which has a wide range of pharmacological effects like anti-tumor and anti-inflammatory effects. This study was intended to investigate the metabolic characteristics of evodiamine in human liver microsomes and hepatocytes by ultra-high performance liquid chromatography coupled with a Q Exactive mass spectrometer. A total of 12 phase I metabolites were detected in human liver microsomes; whereas in human hepatocytes 19 metabolites, including seven phase II metabolites were detected. The structures of the metabolites were characterized based on their accurate masses, fragment ions, and chromatographic retention times. Four metabolites (M1, M2, M5, and M7) were further unambiguously confirmed by matching their retention times, accurate masses, and fragment ions with those of their reference standards. Among these metabolites, 12 metabolites are first identified (M2, M5-M8, M10-M13, and M17-M19). The current study revealed that oxygenation, -demethylation, dehydrogenation, glucuronidation, and GSH conjugation were the major metabolic pathways for evodiamine. This study elucidated the detailed metabolite profiles of evodiamine, which is helpful in predicting metabolism of evodiamine in human and in understanding the elimination mechanism of evodiamine and in turn, the effectiveness and toxicity.