Detection and disposition of tolmetin in the horse

Non-steroidal anti-inflammatory drugs (NSAIDs) are prohibited by the International Federation of Horse Racing Authorities but are commonly used in veterinary practice. Plasma and urinary concentrations of the NSAID tolmetin were determined by a high-performance liquid chromatographic procedure with UV detection following oral administration of a dose of 1 g to six fasted untrained standard bred mares. With a limit of quantitation (LOQ) of 0.05 μg/ml tolmetin was present in plasma for 9–12 h post-administration. Maximum concentrations of 2.1±0.89 μg/ml were found after 0.7±0.25 h. The elimination half-life was 2±1.25 h. Plasma protein binding at concentrations of 0.25 and 2.5 μg/ml was 92±4.9 and 84±4.2%, respectively. As early as 1 h after dosage, tolmetin could be detected in unhydrolysed urine and remained detectable up to 48 h (LOQ=0.5 μg/ml). The maximum concentrations occurred 1.8±0.4 h after administration. The percentage of the dose excreted as unchanged tolmetin within 12 h was 58±7.9%. Neither conjugates nor metabolites could be detected under the experimental conditions studied. For confirmatory analysis in doping control, an LC–MS method was developed. Analysis was performed on an ion trap LC–MS system equipped with an ESI probe in positive MS 2 mode.