In Vivo Metabolic Studies of 2‐Hydroxyethyl Salicylate in Horses

ABSTRACT 2‐Hydroxyethyl salicylate (2HES), a nonsteroidal anti‐inflammatory drug (NSAID), is a medication to treat musculoskeletal injuries and inflammation swelling of humans and horses. Its misuse could affect the performance of horses and mask injuries, which could pose significant health risks. In horseracing, it is reported as an adverse finding once detected in competition. The metabolism of 2HES in either human or horse has not been reported, and therefore, little is known about its metabolic fate. This paper describes the in vivo metabolism of 2HES in horse with an objective to identify the most appropriate target(s) for detecting 2HES administration. To study the elimination and biotransformation of 2HES, topical administrations were performed by giving three castrated horses (geldings) each a total of 100‐g Tensolvet gel (equivalent to 5 g of 2HES). The postulated in vivo metabolites included glucuronide‐conjugated 2HES (2HES‐Glu) and sulphate‐conjugated 2HES (2HES‐SO 4 ) from Phase II conjugation possibly at hydroxyethyl moiety and salicylic acid (SA) from hydrolysis of 2HES. To control the misuse of 2HES in horses effectively, 2HES was found to be the most suitable target. Total 2HES could be detected for up to 10 days in urine, whereas free 2HES could be detected for 16 h in plasma. As the maximum concentration of SA in postadministration urine and plasma sample did not exceed its corresponding international thresholds, monitoring the amount of SA could not be used as an indicator for possible 2HES exposure.