Equine in vivo-derived metabolites of the SARM LGD-4033 and comparison with human and fungal metabolites

Annelie Hansson, Heather K Knych, Scott D Stanley, Emma Berndtson, Liora Jackson, Ulf Bondesson, Mario Thevis, Mikael Hedeland

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

LGD-4033 has been found in human doping control samples and has the potential for illicit use in racehorses as well. It belongs to the pharmacological class of selective androgen receptor modulators (SARMs) and can stimulate muscle growth, much like anabolic steroids. However, SARMs have shown superior side effect profiles compared to anabolic steroids, which arguably makes them attractive for use by individuals seeking an unfair advantage over their competitors. The purpose of this study was to investigate the metabolites formed from LGD-4033 in the horse in order to find suitable analytical targets for doping controls. LGD-4033 was administered to three horses after which plasma and urine samples were collected and analyzed for metabolites using ultra high performance liquid chromatography coupled to a high resolution mass spectrometer. In horse urine, eight metabolites, both phase I and phase II, were observed most of which had not been described in other metabolic systems. Six of these were also detected in plasma. The parent compound was detected in plasma, but not in non-hydrolyzed urine. The longest detection times were observed for unchanged LGD-4033 in plasma and in urine hydrolyzed with β-glucuronidase and is thus suggested as the analytical target for doping control in the horse. The metabolite profile determined in the horse samples was also compared to those of human urine and fungal incubate from Cunninghamella elegans. The main human metabolite, dihydroxylated LGD-4033, was detected in the horse samples and was also produced by the fungus. However, it was a not a major metabolite for horse and fungus, which highlights the importance of performing metabolism studies in the species of interest.

Original languageEnglish (US)
Pages (from-to)91-98
Number of pages8
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume1074-1075
DOIs
StatePublished - Feb 1 2018

Fingerprint

Androgen Receptors
Metabolites
Modulators
Horses
Urine
Testosterone Congeners
Plasmas
Doping (additives)
Fungi
Cunninghamella
Glucuronidase
High performance liquid chromatography
Mass spectrometers
Metabolism
Muscle
High Pressure Liquid Chromatography
Pharmacology
Muscles
Growth

Keywords

  • Doping
  • LGD-4033, Horse
  • Mass Spectrometry
  • Metabolite
  • SARM
  • Selective Androgen Receptor Modulator

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology

Cite this

Equine in vivo-derived metabolites of the SARM LGD-4033 and comparison with human and fungal metabolites. / Hansson, Annelie; Knych, Heather K; Stanley, Scott D; Berndtson, Emma; Jackson, Liora; Bondesson, Ulf; Thevis, Mario; Hedeland, Mikael.

In: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, Vol. 1074-1075, 01.02.2018, p. 91-98.

Research output: Contribution to journalArticle

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abstract = "LGD-4033 has been found in human doping control samples and has the potential for illicit use in racehorses as well. It belongs to the pharmacological class of selective androgen receptor modulators (SARMs) and can stimulate muscle growth, much like anabolic steroids. However, SARMs have shown superior side effect profiles compared to anabolic steroids, which arguably makes them attractive for use by individuals seeking an unfair advantage over their competitors. The purpose of this study was to investigate the metabolites formed from LGD-4033 in the horse in order to find suitable analytical targets for doping controls. LGD-4033 was administered to three horses after which plasma and urine samples were collected and analyzed for metabolites using ultra high performance liquid chromatography coupled to a high resolution mass spectrometer. In horse urine, eight metabolites, both phase I and phase II, were observed most of which had not been described in other metabolic systems. Six of these were also detected in plasma. The parent compound was detected in plasma, but not in non-hydrolyzed urine. The longest detection times were observed for unchanged LGD-4033 in plasma and in urine hydrolyzed with β-glucuronidase and is thus suggested as the analytical target for doping control in the horse. The metabolite profile determined in the horse samples was also compared to those of human urine and fungal incubate from Cunninghamella elegans. The main human metabolite, dihydroxylated LGD-4033, was detected in the horse samples and was also produced by the fungus. However, it was a not a major metabolite for horse and fungus, which highlights the importance of performing metabolism studies in the species of interest.",
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AU - Thevis, Mario

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