Remifentanil (4-methoxycarbonyl-4-[(1-oxopropyl)phyenylamino]-1- piperidinepropionic acid methyl ester) is a μ-opioid receptor agonist with considerable abuse potential in racing horses. The identification of its major equine urinary metabolite, 4-methoxycarbonyl-4-[(1- oxopropyl)phenylamino]-1-piperidinepropionic acid, an ester hydrolysis product of remifentanil is reported. Administration of remifentanil HCl (5 mg, intravenous) produced clear-cut locomotor responses, establishing the clinical efficacy of this dose. ELISA analysis of postadministration urine samples readily detected fentanyl equivalents in these samples. Mass spectrometric analysis, using solid-phase extraction and trimethylsilyl (TMS) derivatization, showed the urine samples contained parent remifentanil in low concentrations, peaking at 1 h. More significantly, a major peak was identified as representing 4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]-1- piperidinepropionic acid, arising from ester hydrolysis of remifentanil. This metabolite reached its maximal urinary concentrations at 1 h and was present at up to 10-fold greater concentrations than parent remifentanil. Base hydrolysis of remifentanil yielded a carboxylic acid with the same mass spectral characteristics as those of the equine metabolite. In summary, these data indicate that remifentanil administration results in the appearance of readily detectable amounts of 4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]- 1-piperidinepropionic acid in urine. On this basis, screening and confirmation tests for this equine urinary metabolite should be optimized for forensic control of remifentanil.
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Supported by grants entitled "Development of a Test for Remifentanil in Horses" from the Association of Racing Commissioners international (ARCI) and research supported by The Equine Drug Council and The Kentucky Racing Commission, Lexington, KY and by research support from the National, Florida and Nebraska Horsemen's Benevolent and Protective Associations and Mrs. John Hay Whitney.
Publication #270 from the Equine Pharmacology and Experimental Therapeutics Program at the Maxwell H. Gluck Equine Research Center and the Department of Veterinary Science, University of Kentucky.
Published as Kentucky Agricultural Experiment Station Article #99-07-145 with the approval of the Dean and Director, College of Agriculture and Kentucky Agricultural Experiment Station.
Lehner, A. F.; Almeida, P.; Jacobs, J.; Harkins, J Daniel; Karpiesiuk, W.; Woods, W. E.; Dirikolu, L.; Bosken, Jeffrey M; Carter, W. G.; Boyles, J.; Holtz, C.; Heller, T.; Nattrass, C.; Fisher, M.; and Tobin, Thomas, "Remifentanil in the Horse: Identification and Detection of its Major Urinary Metabolite" (2000). Maxwell H. Gluck Equine Research Center Faculty Publications. 82.