Investigation Into the Metabolism and Elimination Behavior of RU 58841, and Its Influence on the Steroid Profile in Humans

ABSTRACT

RU 58841 is a nonsteroidal antiandrogen, developed for the treatment of androgen‐dependent conditions. This study aimed to characterize the human metabolism of RU 58841 for the first time and to assess its systemic exposure following topical administration. In an initial in vitro metabolism study, six potential metabolites were identified using liquid chromatography–high resolution (tandem) mass spectrometry (LC‐HRMS/MS). Subsequently, an in vivo administration study was conducted with a RU 58841‐containing hair treatment product, applied once to the scalp of six healthy male volunteers. Dried blood spots (DBS) and urine samples were collected and analyzed by LC‐low resolution MS/MS. Five in vivo‐derived metabolites of RU 58841 were detected in human urine, including products formed via oxidation, N‐dealkylation, and glucuronidation of the parent compound and its phase I metabolites. In DBS, the parent compound and the oxidized metabolite were detected, indicating considerable systemic exposure to topically applied RU 58841. The steroid profile (SP) as part of the Athlete Biological Passport (ABP) was not affected by the administration. These findings provide information about the metabolism and the systemic exposure of RU 58841, and further indicate that a single topical dose of 30 mg does not interfere with SP parameter determinations in routine doping controls.