Investigations Into the Urinary Metabolite Elimination Profile of the Selective Androgen Receptor Modulator S-23 in Studies Mimicking Contaminated Product Ingestion for Doping Control Purposes

Selective androgen receptor modulators (SARMs) have repeatedly been reason of adverse analytical findings (AAFs) in routine doping controls. Among these, S-23 has been identified in five AAFs reported in 2022. In addition to intentional doping, inadvertent exposure through contaminated dietary supplements has emerged as a significant concern, purportedly as well as evidently contributing to AAFs involving SARMs. Thus, the differentiation of inadvertent intake and intentional abuse of S-23 is of growing relevance. This study aimed at investigating the urinary concentration profile of microdosed S-23 and to characterize the elimination pattern. Single and multidose administration studies with 1, 10, and 50 μg of S-23 were conducted, and collected urine samples were analyzed by LC-MS/MS following enzymatic hydrolysis and solid-phase extraction. The analytical method was validated for a semiquantitative detection of S-23 and characterized by a limit of detection of 1 pg/mL. A total of 18 metabolites was detected in human in vivo samples following oral administration of microdosed S-23. Moreover, the study demonstrated that a single dose of 1 μg can be detected for an average of up to 253 h, while a single dose of 50 μg can be detected up to 544 h on average.