Identification of Selected in vitro-Generated Phase-I Metabolites of the Steroidal Selective Androgen Receptor Modulator MK-0773 for Doping Control Purposes

2016 ◽  
Vol 22 (2) ◽  
pp. 49-59 ◽  
Author(s):  
Andreas Lagojda ◽  
Dirk Kuehne ◽  
Oliver Krug ◽  
Andreas Thomas ◽  
Tina Wigger ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Phase I ◽  
Doping Control ◽  
Selective Androgen Receptor Modulator ◽  
Receptor Modulator

Mass spectrometric characterization of the selective androgen receptor modulator (SARM) YK-11 for doping control purposes

2017 ◽  
Vol 31 (14) ◽  
pp. 1175-1183 ◽  
Author(s):  
Mario Thevis ◽  
Thomas Piper ◽  
Josef Dib ◽  
Andreas Lagojda ◽  
Dirk Kühne ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Mass Spectrometric ◽  
Doping Control ◽  
Selective Androgen Receptor Modulator ◽  
Receptor Modulator

Detection of the selective androgen receptor modulator andarine (S-4) in a routine equine blood doping control sample

2015 ◽  
Vol 8 (2) ◽  
pp. 257-261 ◽  
Author(s):  
Adam T. Cawley ◽  
Corrine Smart ◽  
Candace Greer ◽  
Marcus Liu Lau ◽  
John Keledjian
Keyword(s):  
Androgen Receptor ◽  
Control Sample ◽  
Doping Control ◽  
Blood Doping ◽  
Selective Androgen Receptor Modulator ◽  
Receptor Modulator

scholarly journals Investigation of Equine In Vivo and In Vitro Derived Metabolites of the Selective Androgen Receptor Modulator (SARM) ACP-105 for Improved Doping Control

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 85
Author(s):  
Malin Nilsson Broberg ◽  
Heather Knych ◽  
Ulf Bondesson ◽  
Curt Pettersson ◽  
Scott Stanley ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
High Performance ◽  
Metabolite Profile ◽  
In Vitro Models ◽  
Doping Control ◽  
Cunninghamella Elegans ◽  
In Vivo Experiments ◽  
Receptor Modulator

Selective Androgen Receptor Modulators (SARMs) have anabolic properties but less adverse effects than anabolic androgenic steroids. They are prohibited in both equine and human sports and there have been several cases of SARMs findings reported over the last few years. The aim of this study was to investigate the metabolite profile of the SARM ACP-105 (2-chloro-4-[(3-endo)-3-hydroxy-3-methyl-8-azabicyclo[3.2.1]oct-8-yl]-3-methylbenzonitrile) in order to find analytical targets for doping control. Oral administration of ACP-105 was performed in horses, where blood and urine samples were collected over a time period of 96 h. The in vivo samples were compared with five in vitro incubation models encompassing Cunninghamella elegans, microsomes and S9 fractions of both human and equine origin. The analyses were performed using ultra-high performance liquid chromatography coupled to high resolution Q ExactiveTM OrbitrapTM mass spectrometry (UHPLC-HRMS). A total of 21 metabolites were tentatively identified from the in vivo experiments, of which several novel glucuronides were detected in plasma and urine. In hydrolyzed urine, hydroxylated metabolites dominated. The in vitro models yielded several biotransformation products, including a number of monohydroxylated metabolites matching the in vivo results. The suggested analytical target for equine doping control in plasma is a dihydroxylated metabolite with a net loss of two hydrogens. In urine, the suggested targets are two monohydroxylated metabolites after hydrolysis with β-glucuronidase, selected both due to prolongation of the detection time and the availability of reference material from the in vitro models.

scholarly journals Investigations into the elimination profiles and metabolite ratios of micro-dosed selective androgen receptor modulator LGD-4033 for doping control purposes

2021 ◽  
Author(s):  
Felicitas Wagener ◽  
Sven Guddat ◽  
Christian Görgens ◽  
Yiannis S. Angelis ◽  
Michael Petrou ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Limit Of Detection ◽  
Solid Phase ◽  
Doping Control ◽  
Urine Samples ◽  
Selective Androgen Receptor Modulator ◽  
Receptor Modulator ◽  
In Doping ◽  
Qualitative Detection ◽  
Result Management

AbstractLGD-4033 (ligandrol) is a selective androgen receptor modulator (SARM), which is prohibited in sports by the World Anti-Doping Agency (WADA) and led to 62 adverse analytical findings (AAFs) in 2019. But not only deliberate doping with LGD-4033 constitutes a problem. In the past years, some AAFs that concerned SARMs can be attributed to contaminated dietary supplements (DS). Thus, the urgency to develop methods to differentiate between inadvertent doping and abuse of SARMs to benefit from the performance-enhancing effect of the compound in sports is growing. To gain a better understanding of the metabolism and excretion patterns of LGD-4033, human micro-dose excretion studies at 1, 10, and 50 µg LGD-4033 were conducted. Collected urine samples were prepared for analysis using enzymatic hydrolysis followed by solid-phase extraction and analyzed via LC-HRMS/MS. Including isomers, a total of 15 phase I metabolites were detected in the urine samples. The LC-HRMS/MS method was validated for qualitative detection of LGD-4033, allowing for a limit of detection (LOD) of 8 pg/mL. The metabolite M1, representing the epimer of LGD-4033, was synthesized and the structure elucidated by NMR spectroscopy. As the M1/LGD-4033 ratio changes over time, the ratio and the approximate LGD-4033 concentration can contribute to estimating the time point of drug intake and dose of LGD-4033 in doping control urine samples, which is particularly relevant in anti-doping result management. Graphical abstract

Structural elucidation of major selective androgen receptor modulator (SARM) metabolites for doping control

2018 ◽  
Vol 16 (5) ◽  
pp. 698-702 ◽  
Author(s):  
Neeraj Garg ◽  
Annelie Hansson ◽  
Heather K. Knych ◽  
Scott D. Stanley ◽  
Mario Thevis ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Structural Elucidation ◽  
Doping Control ◽  
Selective Androgen Receptor Modulator ◽  
Drug Metabolites ◽  
Receptor Modulator

Elucidated and validated structure of the major SARM doping drug metabolites.

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