Van Eenoo P, Delbeke F T, Roels K, Baert K
Doping Control Unit, Department Pharmacology, Pharmacy and Toxicology, Ghent University, Salisburylaan 133, B-9820, Merelbeke, Belgium.
J Pharm Biomed Anal. 2003 Mar 26;31(4):723-30. doi: 10.1016/s0731-7085(02)00687-8.
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 microg/ml tolmetin was present in plasma for 9-12 h post-administration. Maximum concentrations of 2.1+/-0.89 microg/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 microg/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 microg/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.
非甾体抗炎药（NSAIDs）被国际赛马管理机构联合会禁止使用，但在兽医实践中却常用。给6匹空腹未受过训练的标准品种母马口服1克剂量的NSAID托美丁后，采用高效液相色谱法并结合紫外检测来测定血浆和尿液中托美丁的浓度。给药后9至12小时血浆中托美丁的定量限（LOQ）为0.05微克/毫升。给药后0.7±0.25小时发现最大浓度为2.1±0.89微克/毫升。消除半衰期为2±1.25小时。浓度为0.25微克/毫升和2.5微克/毫升时血浆蛋白结合率分别为92±4.9%和84±4.2%。给药后1小时，在未水解的尿液中就能检测到托美丁，直至48小时仍可检测到（LOQ = 0.5微克/毫升）。最大浓度在给药后1.8±0.4小时出现。12小时内以未改变的托美丁形式排泄的剂量百分比为58±7.9%。在所研究的实验条件下未检测到结合物或代谢物。为了在兴奋剂检测中进行确证分析，开发了一种液相色谱 - 质谱法。分析在配备电喷雾离子化（ESI）探头的离子阱液相色谱 - 质谱系统上以正离子模式的二级质谱（MS(2)）进行。
