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

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

in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, Jahrgang 1074-1075, 01.02.2018, S. 91-98.

Publikationen: Beitrag in FachzeitschriftZeitschriftenaufsätzeForschungBegutachtung

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@article{c28169a7440c4f30af3671531cb2fef9,
title = "Equine in vivo-derived metabolites of the SARM LGD-4033 and comparison with human and fungal metabolites",
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.",
keywords = "Animals, Cunninghamella, Horses, Humans, Limit of Detection, Nitriles, Pyrrolidines, Solid Phase Extraction, Journal Article",
author = "Annelie Hansson and Heather Knych and Scott Stanley and Emma Berndtson and Liora Jackson and Ulf Bondesson and Mario Thevis and Mikael Hedeland",
note = "Copyright {\textcopyright} 2017 Elsevier B.V. All rights reserved.",
year = "2018",
month = feb,
day = "1",
doi = "10.1016/j.jchromb.2017.12.010",
language = "English",
volume = "1074-1075",
pages = "91--98",
journal = "Journal of chromatography. B, Analytical technologies in the biomedical and life sciences",
issn = "1570-0232",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Equine in vivo-derived metabolites of the SARM LGD-4033 and comparison with human and fungal metabolites

AU - Hansson, Annelie

AU - Knych, Heather

AU - Stanley, Scott

AU - Berndtson, Emma

AU - Jackson, Liora

AU - Bondesson, Ulf

AU - Thevis, Mario

AU - Hedeland, Mikael

N1 - Copyright © 2017 Elsevier B.V. All rights reserved.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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.

AB - 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.

KW - Animals

KW - Cunninghamella

KW - Horses

KW - Humans

KW - Limit of Detection

KW - Nitriles

KW - Pyrrolidines

KW - Solid Phase Extraction

KW - Journal Article

U2 - 10.1016/j.jchromb.2017.12.010

DO - 10.1016/j.jchromb.2017.12.010

M3 - Journal articles

C2 - 29334634

VL - 1074-1075

SP - 91

EP - 98

JO - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences

JF - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences

SN - 1570-0232

ER -

ID: 3562768