Detomidine, an α2-adrenergic receptor agonist, is widely employed in horses due to its effective sedative and analgesic properties. The International Federation of Horseracing Authorities prohibits the administration of detomidine during periods that may affect racing performance. It has established the International Screening Limits in plasma at 0.02 ng/mL of its metabolites, 3-hydroxy detomidine. The biotransformation of detomidine involves aliphatic hydroxylation, generating 3-hydroxy detomidine, which subsequently undergoes an additional dehydrogenation reaction to produce 3-carboxy detomidine. Therefore, the detection of 3-carboxy detomidine following 3-hydroxy detomidine suggests a potential enhancement in doping control detection capability. In this study, we investigated the pharmacokinetics of detomidine, and its metabolites following intravenous administration and monitored drug profiles in plasma to prevent substance abuse for doping control. For assessment, the LC-MS/MS method was employed, and the validity of the analytical method was evaluated. The results demonstrated detectable concentrations of detomidine above the lower limit of quantification for 8 hours, and both metabolites were consistently detected throughout the experimental period (48 hours). Monitoring both 3-hydroxy detomidine and 3-carboxy detomidine is considered advantageous for detomidine abuse control. In particular, the calculated long half-life of 3-carboxy detomidine demonstrates its potential as a substance useful for doping tests.

Keywordsdetomidine, 3-hydroxy detomidine, 3-carboxy detomidine, pharmacokinetics, LC-MS, doping control