Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jul 17;25(14):7807.
doi: 10.3390/ijms25147807.

In Vitro and In Vivo Human Metabolism of Ostarine, a Selective Androgen Receptor Modulator and Doping Agent

Omayema Taoussi  1 , Giulia Bambagiotti  1 , Prince Sellase Gameli  1 , Gloria Daziani  1 , Francesco Tavoletta  1 , Anastasio Tini  1 , Giuseppe Basile  2 , Alfredo Fabrizio Lo Faro  1 , Jeremy Carlier  1
Affiliations

In Vitro and In Vivo Human Metabolism of Ostarine, a Selective Androgen Receptor Modulator and Doping Agent

Omayema Taoussi et al. Int J Mol Sci. .

Abstract

Ostarine (enobasarm) is a selective androgen receptor modulator with great therapeutic potential. However, it is also used by athletes to promote muscle growth and enhance performances without the typical adverse effects of anabolic steroids. Ostarine popularity increased in recent years, and it is currently the most abused "other anabolic agent" (subclass S1.2. of the "anabolic agents" class S1) from the World Anti-Doping Agency's (WADA) prohibited list. Several cases of liver toxicity were recently reported in regular users. Detecting ostarine or markers of intake in biological matrices is essential to document ostarine use in doping. Therefore, we sought to investigate ostarine metabolism to identify optimal markers of consumption. The substance was incubated with human hepatocytes, and urine samples from six ostarine-positive cases were screened. Analyses were performed via liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) and software-assisted data mining, with in silico metabolite predictions. Ten metabolites were identified with hydroxylation, ether cleavage, dealkylation, O-glucuronidation, and/or sulfation. The production of cyanophenol-sulfate might participate in the mechanism of ostarine liver toxicity. We suggest ostarine-glucuronide (C25H22O9N3F3, diagnostic fragments at m/z 118, 185, and 269) and hydroxybenzonitrile-ostarine-glucuronide (C25H22O10N3F3, diagnostic fragments at m/z 134, 185, and 269) in non-hydrolyzed urine and ostarine and hydroxybenzonitrile-ostarine (C19H14O4N3F3, diagnostic fragments at m/z 134, 185, and 269) in hydrolyzed urine as markers to document ostarine intake in doping.

Keywords: doping; enobasarm; human metabolism; liquid chromatography–high-resolution mass spectrometry (LC-HRMS); ostarine; selective androgen receptor modulator.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Ostarine high-resolution tandem mass spectrometry spectra after negative electrospray ionization and suggested fragmentation (a) and extracted-ion chromatogram in negative ionization mode of ostarine (dashed line, right y-axis) and metabolites (plain line, left y-axis) after ostarine incubation with 10-donor-pooled human hepatocytes (b). Mass tolerance, 5 ppm.
Figure 2
Figure 2
High-resolution tandem mass spectrometry spectra after negative electrospray ionization and suggested fragmentation of ostarine metabolites. Gluc, glucuronide; Sulf, sulfate; dashed box, uncertain position.
Figure 3
Figure 3
Extracted-ion chromatogram in negative ionization mode of ostarine and metabolites in authentic ostarine-positive urine samples without glucuronide hydrolysis. Mass tolerance, 5 ppm.
Figure 4
Figure 4
Ostarine suggested metabolic fate in humans (only main metabolites). Gluc, glucuronide; dashed box, uncertain position.
See this image and copyright information in PMC

References

    1. Kersey R.D., Elliot D.L., Goldberg L., Kanayama G., Leone J.E., Pavlovich M., Pope H.G. National Athletic Trainers’ Association Position Statement: Anabolic-Androgenic Steroids. J. Athl. Train. 2012;47:567–588. doi: 10.4085/1062-6050-47.5.08. - DOI - PMC - PubMed
    1. Christou M.A., Christou P.A., Markozannes G., Tsatsoulis A., Mastorakos G., Tigas S. Effects of Anabolic Androgenic Steroids on the Reproductive System of Athletes and Recreational Users: A Systematic Review and Meta-Analysis. Sports Med. 2017;47:1869–1883. doi: 10.1007/s40279-017-0709-z. - DOI - PubMed
    1. Todd T. Anabolic Steroids: The Gremlins of Sport. J. Sport. 1987;14:87–107. - PubMed
    1. Maravelias C., Dona A., Stefanidou M., Spiliopoulou C. Adverse Effects of Anabolic Steroids in Athletes: A Constant Threat. Toxicol. Lett. 2005;158:167–175. doi: 10.1016/j.toxlet.2005.06.005. - DOI - PubMed
    1. Pope H.G., Wood R.I., Rogol A., Nyberg F., Bowers L., Bhasin S. Adverse Health Consequences of Performance-Enhancing Drugs: An Endocrine Society Scientific Statement. Endocr. Rev. 2014;35:341–375. doi: 10.1210/er.2013-1058. - DOI - PMC - PubMed

LinkOut - more resources