Metabolism of detomidine in the rat. II. Characterisation of metabolites in urine.
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.
Salonen
J S
JS
Farmos Group Ltd., Research Center, Turku, Finland.
Vuorilehto
L
L
Eloranta
M
M
Karjalainen
A
A
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
D006993:Hypnotics and Sedatives; D007093:Imidazoles; C041255:detomidine