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.
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.
Sun
Xiaohong
X
Department of Analytical Chemistry, Shenyang Pharmaceutical University, PR China.
Niu
Lili
L
Li
Xiaoqin
X
Lu
Xiumei
X
Li
Famei
F
D000818:Animals; D001549:Benzamides / Q000097:blood / Q000378:metabolism*; D001646:Bile / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005243:Feces; D005765:Gastrointestinal Agents / Q000097:blood / Q000378:metabolism*; D008297:Male; D009025:Morpholines / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
D001549:Benzamides; D005765:Gastrointestinal Agents; D009025:Morpholines; C062720:mosapride