Metabolic products and pathway of neferine in rat liver

The present study utilized LC-MS and HPLC approaches to characterize the metabolites of neferine in rat liver after an oral administration of 20 mg·kg~(-1),and investigated the involvement of CYP450 isoforms in the metabolism of neferine by their selective inhibitors in vitro,separately.In positive ionization mode,besides neferine,four metabolites(M_1-M_4) were detected.M_2(the major metabolite) and M_4 were identified as liensinine and isoliensinine by comparison with reference substances.Moreover,according to the analysis of metabolic rule of parent drug(neferine),M_1 and M_3 may be desmethyl-liensinine and desmethyl-isoliensinine,respectively.Furthermore,the metabolism of neferine in rat liver microsomes showed that the percentage inhibition of the major metabolism(liensinine) formation was 80.5% by quinidine(10(μmol·L~(-1)),selective CYP2D1 inhibitor) and 25.7% by ketoconazole((1 μmol·L~(-1)),selective CYP3A1 inhibitor).Neferine was mainly metabolized by CYP2D1 or CYP3A1 to liensinine,isoliensinine,desmethyl-liensinine and desmethyl-isoliensinine.