Evidence for electrophilic properties of N2-methyl-9-hydroxy ellipticinium acetate (Celiptium) from human biliary metabolites.

The human biliary metabolism of the antitumor agent N2-methyl-9-hydroxyellipticinium acetate is described. Three major compounds have been identified by high-performance liquid chromatography and comparison with synthetic reference derivatives: the unchanged drug, the O-glucuronide conjugate and the cysteinyl-ellipticinium adduct. The latter one is the expected detoxification compound of an intermediate electrophilic quinone-imine derivative generated in vivo. This result provides a further evidence that hydroxylated forms of ellipticine derivatives might be activated by a biooxidation route.