title: Metabolism of detomidine in the rat. II. Characterisation of metabolites in urine.
abstract: In order to investigate the biotransformation of a new alpha 2-adrenoceptor agonist, detomidine, metabolites were isolated from rat urine by solid phase extraction and purified by TLC. The isolated compounds were structurally analysed by 1H-NMR, MS and GC-MS as such or as their methyl and/or silyl derivatives. In addition to detomidine, which was found in trace amounts, four major metabolites were identified: hydroxymethyldetomidine, the corresponding O-glucuronide, detomidine carboxylic acid, and detomidine mercapturate. Together the identified components make up about 80% of urinary detomidine derived compounds. On the basis of these findings a major biotransformation pathway could be suggested. The reaction sequence is initiated by a hydroxylation. Subsequent glucuronidation, glutathione conjugation or secondary oxidation divide the route into three branches each producing one of the other three identified metabolites.
authors.affiliation: Farmos Group Ltd., Research Center, Turku, Finland.
authors.forename: J S
authors.initials: JS
authors.lastname: Salonen
authors.forename: L
authors.initials: L
authors.lastname: Vuorilehto
authors.forename: M
authors.initials: M
authors.lastname: Eloranta
authors.forename: A
authors.initials: A
authors.lastname: Karjalainen
mesh_terms: D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D006993:Hypnotics and Sedatives / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine; D007093:Imidazoles / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D011919:Rats, Inbred Strains; D012015:Reference Standards
chemical_list: D006993:Hypnotics and Sedatives; D007093:Imidazoles; C041255:detomidine