No abstract

All 3 drugs showed similar effects in relation to anaesthetic induction and recovery qualities and cardiopulmonary responses. However, alfaxalone and thiopental prolonged recovery time compared with ketamine.

Rationale GW1516 is a peroxisome proliferator‐activated receptor‐δ agonist in the class of hormones and metabolic modulators. The use of GW1516 is banned in both horseracing and equestrian competitions. To the best of our knowledge, this is the first metabolic study of GW1516 in horses. Methods After protein precipitation of pre‐ and post‐administration plasma GW1516 samples, the supernatants were analyzed using liquid chromatography/electrospray ionization Q‐Exactive high‐resolution mass spectrometry to detect GW1516 and its metabolites. Monoisotopic ions of GW1516 and its metabolites were monitored from the full‐scan mass spectral data of pre‐ and post‐administration samples. Quantification methods were developed and validated to establish the elimination profiles of GW1516, its sulfoxide, and its sulfone in equine plasma. Results GW1516 and its four metabolites GW1516 sulfoxide, GW1516 sulfone, 5‐(hydroxymethyl)‐4‐methyl‐2‐(4‐trifluoromethylphenyl)thiazole (HMTT), and M1 were detected in post‐administration plasma samples. GW1516 sulfoxide, GW1516 sulfone, and HMTT were identified by comparison with their respective reference standards whereas M1 was tentatively identified as 4‐methyl‐2‐[4‐(trifluoromethyl)phenyl]‐1,3‐thiazole‐5‐carboxylic acid by mass spectral interpretation. GW1516 had the longest detection time in post‐administration plasma. The elimination profiles of GW1516, its sulfoxide, and its sulfone in plasma were established. Conclusions For the purpose of doping control, GW1516 is recommended as the target analyte to be monitored in equine plasma due to its long detection time (around 1 week) and the ready availability of its reference material.

The use of nicotine stimulants in horses is generally banned in horse racing and equestrian sports-accidental consumption of tobacco products is one of the possible causes of nicotine exposure in horses. The authors recently reported a comprehensive metabolic study of nicotine in equines, differentiating between nicotine exposure and sample contamination by means of a nicotine biomarker trans-3 0hydroxycotinine. To identify potential biomarkers for the differentiation of genuine nicotine administration and consumption of tobacco products, tobacco leaves (equivalent to 250 mg of nicotine) were nasoesophageally administered to three thoroughbred mares. Quantification methods of anatabine in plasma and urine were newly developed and validated and successfully applied to postadministration samples. Previously reported simultaneous quantification methods of eight target analytes including nicotine and its metabolites in plasma and urine were also applied to the samples.The results demonstrate that both trans-3 0 -hydroxycotinine and anatabine could be used as potential biomarkers in equine urine and plasma to indicate recent exposure to tobacco products in horses. As well, trans-3 0 -hydroxycotinine had the longest halflife as a detectable metabolite in urine and plasma. To our knowledge, this is the first report of a comprehensive study of tobacco product detection in horses.

Rationale GW1516 is a peroxisome proliferator‐activated receptor‐δ (PPAR‐δ) agonist that is banned in horseracing and equestrian sports. Long‐term detection and longitudinal distribution of GW1516 in the mane of a horse are reported for the first time and this hair analysis could prolong the detection window of GW1516 for doping control. Methods Mane hairs were divided into three segments (0–7, 7–15, and >15 cm from the cut end) and completely pulverized and homogenized for analysis. The pulverized hair samples were extracted with methanol followed by further purification and the extracts were analyzed by liquid chromatography/electrospray ionization high‐resolution mass spectrometry (LC/ESI‐HRMS) using a Q‐Exactive instrument. This method was successfully validated and applied to post‐administration samples to confirm the presence of GW1516 and its metabolites and estimate the uptake amounts of GW1516. Results After administration of 150 mg of GW1516 to a thoroughbred mare, GW1516 was detected in one of two segments of all mane hairs, and four metabolites, namely GW1516 sulfoxide, GW1516 sulfone, 5‐(hydroxymethyl)‐4‐methyl‐2‐(4‐trifluoromethylphenyl)thiazole (HMTT), and 4‐methyl‐2‐[4‐(trifluoromethyl)phenyl]‐1,3‐thiazole‐5‐carboxylic acid (MTTC), were also identified. The longitudinal distribution analysis results showed that the maximum uptake of GW1516 into hair (approximately 0.05 pg/mg) was observed at around 13 weeks post‐administration and GW1516 could be detected and confirmed up to 6 months post‐administration. Conclusions The parent drug GW1516 was identified as the most appropriate monitoring target in equine hair for controlling its misuse in horses. The use of hair analysis could extend the detection time of GW1516 to at least 6 months after the administration of 150 mg of GW1516 to a thoroughbred mare.