Summary
In order to investigate the biotransformation of a new a2-adrenoceptor agonist, detomidine, metabolites were isolated from rat urine by solid phase extraction and purified by TLC. The isolated compounds were structurally analysed by1H-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.
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Salonen, J.S., Vuorilehto, L., Eloranta, M. et al. Metabolism of detomidine in the rat II. Characterisation of metabolites in urine. European Journal of Drug Metabolism and Pharmacokinetics 13, 59–65 (1988). https://doi.org/10.1007/BF03189930
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DOI: https://doi.org/10.1007/BF03189930