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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Jul 27

PMID 39063049

Authors

Omayema Taoussi

Giulia Bambagiotti

Prince Sellase Gameli

Gloria Daziani

Francesco Tavoletta

Anastasio Tini

Giuseppe Basile

Alfredo Fabrizio Lo Faro

Jeremy Carlier

Affiliations

Soon will be listed here.

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, -glucuronidation, and/or sulfation. The production of cyanophenol-sulfate might participate in the mechanism of ostarine liver toxicity. We suggest ostarine-glucuronide (CHONF, diagnostic fragments at / 118, 185, and 269) and hydroxybenzonitrile-ostarine-glucuronide (CHONF, diagnostic fragments at / 134, 185, and 269) in non-hydrolyzed urine and ostarine and hydroxybenzonitrile-ostarine (CHONF, diagnostic fragments at / 134, 185, and 269) in hydrolyzed urine as markers to document ostarine intake in doping.

Citing Articles

Bioanalytical methods in doping controls: a review.

Thomas A, Walpurgis K, Naumann N, Piper T, Thevis M Bioanalysis. 2025; 17(5):359-370.

PMID: 39916648 PMC: 11875490. DOI: 10.1080/17576180.2025.2460951.

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