title: [Isolation and identification of a major metabolite of SFZ-47 in the rabbit urine].
abstract: OBJECTIVE
  To isolate and identify a glucuronide metabolite of SFZ-47 [3H-1,2-dihydro-2-(4-methyl-phenylamino)methyl-1-pyrrolizinone], which is difficult to synthesize because it undergoes hydrolysis and intramolecular acyl migration at physiological pH, in rabbit urine.
  
  
  METHODS
  Two rabbits were ig 200 mg doses of SFZ-47. Urine was collected for 24 h, adjusted to pH 4.0 with acetic acid and lyophilized. The residues were reconstituted in 25 mL methanol and centrifuged at 5,000 r.min-1 for 10 min. The supernatant was filtered (0.45 micron) and then isolated with semi-preparative reversed phase HPLC. The eluent collected from individual peaks was evaporated by rotary evaporation and freeze-drying. Compounds were then identified with electrospray ion trap mass spectrometry and 1HNMR spectroscopy.
  
  
  RESULTS
  The 1HNMR and ESI-MSn results indicate that the metabolite is the 1-O-acyl beta-D-glucuronide conjugate of 4-(3H-1,2-dihydro-1-pyrrolizinone-2-methylamino) benzoic acid.
  
  
  CONCLUSIONS
  This method was shown to be rapid and simple and gave excellent resolution from endogenous constituents in urine, and it is suitable for preparation of the glucuronide metabolites of SFZ-47 and its analogues.
authors.affiliation: Laboratory of Drug Metabolism, College of Life Science, Jilin University, Changchun 130023, China. gujingkai@163.net
authors.forename: Qing-guang
authors.initials: QG
authors.lastname: Dong
authors.forename: Jing-kai
authors.initials: JK
authors.lastname: Gu
authors.forename: Da-fang
authors.initials: DF
authors.lastname: Zhong
authors.forename: Da-feng
authors.initials: DF
authors.lastname: Chu
authors.forename: Lu
authors.initials: L
authors.lastname: Sun
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D008297:Male; D015394:Molecular Structure; D011758:Pyrroles / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D011817:Rabbits; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: C460139:3H-1,2-dihydro-2-(4-methylphenylamino)methyl-1-pyrrolizinone; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011758:Pyrroles