Microbial metabolism of evodiamine by Penicillium janthinellum and its application for metabolite identification in rat urine

Microbial metabolism of evodiamine by Penicillium janthinellum AS 3.510 was investigated. Two metabolites were isolated from the broth and their structures were identified as 10-hydroxyevodiamine and 11-hydroxyevodiamine, by means of their IR, MS and NMR spectral data. Both of the metabolites were proved to be new compounds and showed strong cytotoxic activity in cytotoxicity assay. A major in vivo metabolite of evodiamine was detected in rat urine after oral administration of evodiamine and its structure was proved to be identical with that of the microbial metabolite 10-hydroxyevodiamine by HPLC–MS/MS analysis and comparison with the reference standard. The time course of microbial transformation of evodiamine and its urinary excretion in rat was proposed.