Hao Liu, Siyuan Guo, Shuyi Xi
Sep 13, 2022
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Biomedical chromatography : BMC
Abstract
Graveoline is a biologically active ingredient extracted from Ruta graveolens. Current work aimed at investigating in vitro metabolism of graveoline by rat or human liver microsomes and hepatocytes. Graveoline (20 μM) was incubated with NADPH-supplemented rat and human liver microsome as well as hepatocytes. Liquid chromatography coupled to photo diode array detector and quadrupole/time-of-flight tandem mass spectrometry was used to detect and identify the generated metabolites. The structures of the metabolites were identified by accurate mass, elemental composition as well as indicative fragment ions. A total of 12 metabolites were obtained, including 6 phase I and 6 phase II metabolites. The metabolic pathways included demethylenation, demethylation, hydroxylation, glucuronidation and GSH conjugation. The metabolite (M10) produced by opening ring of the methylenedioxyphenyl moiety was detected as the most abundant in both liver microsomes and hepatocytes, mainly catalyzed by CYP1A2, 2C8, 2C9, 2C19, 2D6, 3A4 and 3A5. This study provides valuable information with respect to the in vitro metabolism of graveoline, which is indispensable for further development and safety evaluation of this compound.