Use of an Electrochemically Synthesised Metabolite of a Selective Androgen Receptor Modulator for Mass Spectrometry-Based Sports Drug Testing

Abstract

The elucidation of the metabolism of new therapeutics is a major task for pharmaceutical companies and of great interest for drug testing laboratories. The latter in particular need to determine the presence or absence of drugs or their metabolic products in urine to test for a misuse of these compounds. Commonly, in vitro or animal models are used to mimic the human metabolism and produce potential targets in amounts allowing for method development. An alternative route based on electrochemical reactions of drugs was reported to allow for the generation of selected metabolites. The utility of this approach for doping control purposes was demonstrated with a novel class of anabolic agents termed selective androgen receptor modulators (SARMs). An arylpropionamide-derived drug candidate was subjected to electrochemical “metabolism” and a major phase-I-metabolite, resulting from the elimination of a substituted phenol residue as identified in in vitro experiments, was generated and characterised using liquid chromatography/nuclear magnetic resonance spectroscopy and high resolution/high accuracy mass spectrometry. The metabolite was included in routine doping control procedures based on liquid chromatography/tandem mass spectrometry and has served as a reference compound for 5000 doping control specimens.