Characterization of metabolic profile of mosapride citrate in rat and identification of two new metabolites: Mosapride N-oxide and morpholine ring-opened mosapride by UPLC-ESI-MS/MS.

Research paper by Xiaohong X Sun, Lili L Niu, Xiaoqin X Li, Xiumei X Lu, Famei F Li

Indexed on: 14 Apr '09Published on: 14 Apr '09Published in: Journal of Pharmaceutical and Biomedical Analysis


The identification and structure elucidation of metabolites of mosapride, a selective gastroprokinetic agent, was investigated in rats. After oral administration, samples of rat urine, bile, feces and plasma were collected and analyzed by a selective UPLC-ESI-MS/MS method. Altogether 18 metabolites were detected and at least 15 metabolites were reported in rat for the first time. Two new metabolites, mosapride N-oxide in rat bile, urine and plasma, morpholine ring-opened mosapride in plasma and feces, were identified by comparison with the reference standards. One known major mammalian metabolite, des-p-fluorobenzyl mosapride, was also identified. The molecular structures of nine phase I metabolites and six phase II metabolites of mosapride were elucidated based on the characteristics of their protonated molecular ions, product ions and chromatographic retention times. The phase I metabolites were mainly transformed by four main metabolism pathways, dealkylation, N-oxidation, morpholine ring cleavage and hydroxylation, with dealkylation as the predominant metabolic pathway, while phase II metabolites were mainly formed by glucuronidation. The relatively comprehensive metabolic pathway of mosapride was proposed.