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Metabolic study of GW1516 in equine urine using liquid chromatography/electrospray ionization Q‐Exactive high‐resolution mass spectrometry for doping control
Author(s) -
Ishii Hideaki,
Shibuya Mariko,
Leung Gary NgaiWa,
Yamashita Shozo,
Yamada Masayuki,
Kushiro Asuka,
Kasashima Yoshinori,
Okada Jun,
Kawasaki Kazumi,
KijimaSuda Isao
Publication year - 2021
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.9028
Subject(s) - chemistry , chromatography , sulfone , sulfoxide , mass spectrometry , urine , electrospray ionization , metabolite , thiazole , organic chemistry , biochemistry
Rationale The use of GW1516, a peroxisome proliferator‐activated receptor δ (PPAR δ) agonist, is strictly prohibited in both horseracing and equestrian competitions. However, little is known about its metabolic fate in horses. To the best of our knowledge, this is the first reported metabolic study of GW1516 in equine urine. Methods Urine samples obtained from a thoroughbred after nasoesophageal administration with GW1516 were protein‐precipitated and the supernatants were subsequently analyzed by liquid chromatography/electrospray ionization high‐resolution mass spectrometry (LC/ESI‐HRMS) with a Q‐Exactive mass spectrometer. Monoisotopic ions of GW1516 and its metabolites were monitored from the full‐scan mass spectral data of pre‐ and post‐administration samples. A quantification method was developed and validated to establish the excretion profiles of GW1516, its sulfoxide, and its sulfone in equine urine. Results GW1516 and its nine metabolites [including GW1516 sulfoxide, GW1516 sulfone, 5‐(hydroxymethyl)‐4‐methyl‐2‐(4‐trifluoromethylphenyl)thiazole (HMTT), methyl 4‐methyl‐2‐[4‐(trifluoromethyl)phenyl]‐1,3‐thiazole‐5‐carboxylate (MMTC), 4‐methyl‐2‐[4‐(trifluoromethyl)phenyl]‐1,3‐thiazole‐5‐carboxylic acid (MTTC), and M1 to M4] were detected in post‐administration urine samples. GW1516 sulfoxide and GW1516 sulfone showed the longest detection times in post‐administration urine samples and were therefore recommended as potential screening targets for doping control purposes. Quantitative analysis was also conducted to establish the excretion profiles of GW1516 sulfoxide and GW1516 sulfone in urine. Conclusions For the purposes of doping control of GW1516, the GW1516 sulfoxide and GW1516 sulfone metabolites are recommended as the target analytes to be monitored in equine urine due to their high specificities, long detection times (1 and 4 weeks, respectively), and the ready availability of their reference materials.