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The detection and biotransformation of guanabenz in horses: a preliminary report.

Abstract: Guanabenz (2,6-dichlorobenzylidene-amino-guanidine) is a centrally acting antihypertensive drug whose mechanism of action is via alpha2 adrenoceptors or, more likely, imidazoline receptors. Guanabenz is marketed as an antihypertensive agent in human medicine (Wytensin tablets, Wyeth Pharmaceuticals). Guanabenz has reportedly been administered to racing horses and is classified by the Association of Racing Commissioners International as a class 3 foreign substance. As such, its identification in a postrace sample may result in significant sanctions against the trainer of the horse. The present study examined liquid chromatographic/tandem quadrupole mass spectrometric (LC-MS/MS) detection of guanabenz in serum samples from horses treated with guanabenz by rapid i.v. injection at 0.04 and 0.2 mg/kg. Using a method adapted from previous work with clenbuterol, the parent compound was detected in serum with an apparent limit of detection of approximately 0.03 ng/ml and the limit of quantitation was 0.2 ng/ml. Serum concentrations of guanabenz peaked at approximately 100 ng/ml after the 0.2 mg/kg dose, and the parent compound was detected for up to 8 hours after the 0.04 mg/kg dose. Urine samples tested after administration of guanabenz at these dosages yielded evidence of at least one glucuronide metabolite, with the glucuronide ring apparently linked to a ring hydroxyl group or a guanidinium hydroxylamine. The LC-MS/MS results presented here form the basis of a confirmatory test for guanabenz in racing horses.
Publication Date: 2003-09-25 PubMed ID: 14506596
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Validation Study

Summary

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This study explores the detection and changes in the antihypertensive drug Guanabenz when administered to horses. Using chromatography and mass spectrometry methods, the research found that it is possible to detect Guanabenz in horse serum.

Research Overview

  • The research revolves around Guanabenz, a drug primarily used as an antihypertensive agent in humans. It has reportedly been administered to racing horses, which led to this study’s investigation into its quantification in horses’ serum and urine, and the changes it undergoes within the horse’s body.
  • The findings from this research are of significant importance to the horse racing industry, as the detection of class 3 foreign substances such as Guanabenz can result in severe penalties for the horse’s trainer.

Research Methodology

  • The study employed liquid chromatographic/tandem quadrupole mass spectrometric (LC-MS/MS) to detect Guanabenz in serum samples from horses treated with the drug via intravenous administration at varying dosages.
  • The researchers adapted a method previously used in work with another drug named Clenbuterol to make this detection possible and analyzable.
  • The researchers also tested urine samples after administering the drug to discover any metabolites of Guanabenz in the horses’ bodies.

Research Findings

  • The study found that the Guanabenz parent compound could be detected in horse serum with an apparent limit of detection of approximately 0.03 ng/ml and a limit of quantitation of 0.2 ng/ml.
  • Guanabenz concentrations in the serum peaked at around 100 ng/ml after a 0.2 mg/kg dose was administered, and the drug could still be detected up to eight hours post-administration of a 0.04 mg/kg dose.
  • The testing of urine samples revealed evidence of at least one glucuronide metabolite, suggesting that Guanabenz undergoes biotransformation within the horse’s body.

Conclusion

  • Through the research findings, the study has paved the way for developing a confirmatory test for the presence of Guanabenz in horse racing, which can potentially alleviate the industry’s concerns about illegal drug use and maintain ethical standards.

Cite This Article

APA
Harkins JD, Dirikolu L, Lehner AF, Hughes C, Schroedter D, Mayer B, Bratton C, Fisher MV, Tobin T. (2003). The detection and biotransformation of guanabenz in horses: a preliminary report. Vet Ther, 4(2), 197-209.

Publication

ISSN: 1528-3593
NlmUniqueID: 100936368
Country: United States
Language: English
Volume: 4
Issue: 2
Pages: 197-209

Researcher Affiliations

Harkins, J Daniel
  • Maxwell H. Gluck Equine Research Center and the Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.
Dirikolu, Levent
    Lehner, Andreas F
      Hughes, Charlie
        Schroedter, Dwight
          Mayer, Brent
            Bratton, Calvert
              Fisher, Mitzi V
                Tobin, Thomas

                  MeSH Terms

                  • Animals
                  • Antihypertensive Agents / administration & dosage
                  • Antihypertensive Agents / blood
                  • Antihypertensive Agents / pharmacokinetics
                  • Area Under Curve
                  • Chromatography, High Pressure Liquid / veterinary
                  • Female
                  • Guanabenz / administration & dosage
                  • Guanabenz / blood
                  • Guanabenz / pharmacokinetics
                  • Horses / metabolism
                  • Injections, Intravenous / veterinary
                  • Mass Spectrometry / standards
                  • Mass Spectrometry / veterinary
                  • Reference Standards
                  • Sports

                  Citations

                  This article has been cited 1 times.
                  1. Chen Y, Palczewska G, Mustafi D, Golczak M, Dong Z, Sawada O, Maeda T, Maeda A, Palczewski K. Systems pharmacology identifies drug targets for Stargardt disease-associated retinal degeneration. J Clin Invest 2013 Dec;123(12):5119-34.
                    doi: 10.1172/JCI69076pubmed: 24231350google scholar: lookup