Analysis of Hypaconitine’s Metabolites and Related Metabolic CYP Isoforms in Rat Liver Microsomal by UPLC-MS/MS

Hypaconitine (HA) is a diester-diterpene type aconitum alkaloid, a potential toxicity alkaloid extracted from Aconitum longtounense T. In this study, the hypaconitine’s metabolites in rat liver microsomes were determined by UPLC-MS/MS and a high resolution mass spectrogram (HRMS) method. Sulfaphenazole, α-naphthoflavone, quinidine, ketoconazole, ammonium diethyldithiocarbamate were applied as specific inhibitors for CYP3A、CYP1A2、CYP2D6、CYP3A and CYP2E1 in rat liver microsomes. The results show that seven metabolites of hypaconitine were found and characterized in rat liver microsomal incubations. These metabolites were deduced as 15-dehydrate-HA, 8-O-deacetyl-HA, 2-hydroxyl-HA, mesaconitine, 1-O-demethyl-HA, 18-O-demethyl-HA, hydroxyl-8-deacetyl-HA, respectively. Hypaconitine was mainly metabolized by CYP3A. CYP2C， CYP1A2，CYP2D and CYP2E1 were important CYP isoforms responsible for the metabolism reaction of hypaconitine.