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Aminorex and rexamino as metabolites of levamisole in the horse.
Abstract: Administration studies of levamisole in horses were carried out using two different levamisole preparations, namely, levamisole hydrochloride oral bolus and levamisole phosphate injectable solution. These preparations were analysed in detail for the presence of aminorex-like impurities. Both levamisole preparations were found to contain 1-(2-mercaptoethyl)-4-phenyl-2-imidazolidinone (I) and 4-phenyl-2-imidazolidinone (II) as degradation impurities, but neither aminorex nor rexamino was detected in these preparations. After the administration of these preparations to horses, aminorex, rexamino, in addition to levamisole and compound II, were detected in post-administration urine and plasma samples, among which compound II was found to have the longest detection time. Administration study of compound II was then performed on another horse to investigate whether it could be a metabolic precursor of aminorex and/or rexamino. However, no aminorex and rexamino was detected in the post-administration samples, suggesting that compound II was not a metabolic precursor of aminorex or rexamino. A metabolite (III) of compound II, tentatively identified to be a hydrolysis product of compound II, was observed instead. It has been established unequivocally that the normal use of levamisole products in horses can lead to the presence of aminorex, rexamino and 4-phenyl-2-imidazolidinone (II) in their urine and blood samples. As compound II has the longest detection time, the detection of aminorex (and in some cases rexamino) in some of the official samples from racehorses can be ascribed to the use of levamisole products as long as compound II is also present as a marker. These findings should be of direct relevance to the investigation of some of the cases of aminorex detection in official doping control samples from racehorses.
Publication Date: 2009-03-02 PubMed ID: 19298880DOI: 10.1016/j.aca.2009.02.033Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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The research examined the presence of aminorex and rexamino, substances related to banned stimulants, in horses after the administration of levamisole, a commonly used medication in equine health. Levamisole and its degradation impurities were studied and found to not be the metabolic precursors of aminorex or rexamino.
Study Details and Methods
- The researchers conducted administration studies of levamisole in horses using two different preparations – levamisole hydrochloride oral bolus and levamisole phosphate injectable solution.
- These levamisole preparations were analysed in detail for the presence of aminorex-like impurities.
- Both levamisole preparations were found to contain specific degradation impurities, but not aminorex or rexamino.
- After the administration of these preparations, the horses’ urine and plasma samples were analysed.
Findings
- Following the administration of levamisole to horses, aminorex, rexamino, in addition to levamisole and one of its degradation impurities, were detected in post-administration urine and plasma samples.
- One degradation impurity was found to persist longer in the horse’s system, marking the longest detection time.
- In another study, the researchers found no aminorex and rexamino in samples after compound II administration, indicating it wasn’t the metabolic precursor of aminorex or rexamino.
Implications
- The normal use of levamisole products in horses can lead to the presence of aminorex, rexamino, and the degradation impurity in their urine and blood samples.
- The presence of aminorex (and in some cases rexamino) in some of the official racehorse samples could be due to the use of levamisole products, supported by the presence of the long-lasting degradation impurity as a marker.
- The findings could have relevance to the investigation of some cases of aminorex detection in official doping control samples from racehorses.
Cite This Article
APA
Ho EN, Leung DK, Leung GN, Wan TS, Wong AS, Wong CH, Soma LR, Rudy JA, Uboh C, Sams R.
(2009).
Aminorex and rexamino as metabolites of levamisole in the horse.
Anal Chim Acta, 638(1), 58-68.
https://doi.org/10.1016/j.aca.2009.02.033 Publication
Researcher Affiliations
- Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N.T., Hong Kong, China. emmie.nm.ho@hkjc.org.hk
MeSH Terms
- Administration, Oral
- Aminorex / analysis
- Aminorex / blood
- Aminorex / urine
- Animals
- Chromatography, Liquid
- Doping in Sports
- Gas Chromatography-Mass Spectrometry
- Horses / metabolism
- Levamisole / administration & dosage
- Levamisole / analysis
- Levamisole / metabolism
- Stereoisomerism
- Tandem Mass Spectrometry
- Tin Compounds / chemistry
Citations
This article has been cited 9 times.- Kudrimoti S, Machin J, Arojojoye AS, Awuah SG, Eisenberg R, Fenger C, Maylin G, Lehner AF, Tobin T. Synthesis and characterization of d(5) -barbarin for use in barbarin-related research. Drug Test Anal 2023 Jan;15(1):42-46.
- Campillo JT, Eiden C, Boussinesq M, Pion SDS, Faillie JL, Chesnais CB. Adverse reactions with levamisole vary according to its indications and misuse: A systematic pharmacovigilance study. Br J Clin Pharmacol 2022 Mar;88(3):1094-1106.
- Maylin G, Fenger C, Machin J, Kudrimoti S, Eisenberg R, Green J, Tobin T. Aminorex identified in horse urine following consumption of Barbarea vulgaris; a preliminary report. Ir Vet J 2019;72:15.
- Solomon N, Hayes J. Levamisole: A High Performance Cutting Agent. Acad Forensic Pathol 2017 Sep;7(3):469-476.
- Maier J, Mayer FP, Brandt SD, Sitte HH. DARK Classics in Chemical Neuroscience: Aminorex Analogues. ACS Chem Neurosci 2018 Oct 17;9(10):2484-2502.
- Lewis JA, Yakel JL, Pandya AA. Levamisole: A Positive Allosteric Modulator for the α3β4 Nicotinic Acetylcholine Receptors Prevents Weight Gain in the CD-1 Mice on a High Fat Diet. Curr Pharm Des 2017;23(12):1869-1872.
- Arora NP, Jain T, Bhanot R, Natesan SK. Levamisole-induced leukocytoclastic vasculitis and neutropenia in a patient with cocaine use: an extensive case with necrosis of skin, soft tissue, and cartilage. Addict Sci Clin Pract 2012 Sep 24;7(1):19.
- Gulati S, Donato AA. Lupus anticoagulant and ANCA associated thrombotic vasculopathy due to cocaine contaminated with levamisole: a case report and review of the literature. J Thromb Thrombolysis 2012 Jul;34(1):7-10.
- Gutierrez J, Eisenberg RL, Koval NJ, Armstrong ER, Tharappel J, Hughes CG, Tobin T. Pemoline and tetramisole 'positives' in english racehorses following levamisole administration. Ir Vet J 2010 Aug 1;63(8):498.
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