Isolation and identification of the glucuronide of 4-(3H-1,2-dihydro-1-pyrrolizinone-2-methylamino)benzoic acid from rabbit urine.
The metabolic profile of 3H-1,2-dihydro-2-(4-methylphenylamino)methyl-1-pyrrolizinone (SFZ-47), a putative non-steroidal anti-inflammatory pro-drug, has been studied in rabbit urine. Semi-preparative reversed-phase HPLC of 24 h urine from two rabbits given single oral doses of SFZ-47 (200 mg) allowed the separation of SFZ-47 together with the oxidative metabolite 4-(3H-1,2-dihydro-1-pyrrolizinone-2-methylamino)benzoic acid (SFZ-47-COOH) and its glucuronide conjugate. The glucuronide was characterized by ESI-MS(n) and (1)H NMR and shown to be the 1-O-acyl beta-D-glucuronide conjugate of SFZ-47-COOH. The method gave excellent resolution of the glucuronide from endogenous constituents in urine and may be suitable for the preparation of glucuronide metabolites of other drugs.
Dong
Qingguang
Q
Laboratory of Drug Metabolism, College of Life Science, Jilin University, Jiefang Road 123, Changchun, 130023, China.
Gu
Jingkai
J
Zhong
Dafang
D
Paul Fawcett
J
J
Chu
Dafeng
D
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000652:urine*; D020719:Glucuronides / Q000652:urine*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011758:Pyrroles / Q000652:urine*; D011817:Rabbits; D021241:Spectrometry, Mass, Electrospray Ionization
C460139:3H-1,2-dihydro-2-(4-methylphenylamino)methyl-1-pyrrolizinone; D000894:Anti-Inflammatory Agents, Non-Steroidal; D020719:Glucuronides; D011758:Pyrroles