Plasma and Urinary Elimination Profiles of Medetomidine Metabolites in Horses for the Purpose of Doping and Medication Control

Medetomidine, an α₂-adrenergic agonist, is widely used as a sedative in horses. While its pharmacological effects are established, limited data exist on elimination of its metabolites, 3'-hydroxy medetomidine (HMD) and 3'-carboxy medetomidine (CMD), which are of regulatory interest. HMD is currently targeted in plasma and urine under International Screening Limits (ISLs) established by the International Federation of Horseracing Authorities (IFHA). In this study, seven Thoroughbreds received 6.3 μg/kg of medetomidine intravenously. Blood and urine were collected for 96 h and analyzed by LC-MS/MS after solid-phase extraction with and without enzymatic hydrolysis. Parent drug was detectable in plasma up to 4 h but absent in urine. HMD was quantifiable in plasma to 48 h and urine to 72 h, while CMD, with a distinct profile, was measurable in plasma to 32 h and urine to 72 h. Based on the ISLs, the detection times (DTs) for both plasma and urine were 48 h. Pharmacokinetic modeling estimated clearance at 2.15 L/h/kg and steady-state distribution volume at 1.90 L/kg. These findings show rapid clearance of medetomidine and extended metabolite excretion. The DT of HMD aligns with loss of pharmacological effect, supporting current ISLs and reinforcing the rationale for targeting HMD, with CMD providing supplementary regulatory insight.