5 alpha-reductase inhibitors: Evaluation of their potential confounding effect on GC-C-IRMS doping analysis

5 alpha-reductase inhibitors (5-ARIs) are considered by the World Anti-doping Agency as potential confounding factors in evaluating the athlete steroid profile, since they may interfere with the urinary excretion of several diagnostic compounds. We herein investigated 5 alpha-reductase inhibitors from a different perspective, by verifying their influence on the carbon isotopic composition of 5 alpha- and 5 beta-reduced testosterone and nandrolone metabolites. The GC-C-IRMS analysis was performed on a set of urine samples collected from three male Caucasian volunteers after the acute and chronic administration of finasteride in combination with the intake of 19-norandrostenedione, a nandrolone precursor. The excretion and the isotopic profile of androsterone (A), etiocholanolone (Etio) 5 alpha-androstane-3 alpha,17 beta-diol (5 alpha Adiol), and 5 beta-androstane-3 alpha,17 beta-diol (5 beta Adiol) were determined as well as those of 19-norandrosterone (19-NA) and 19-noretiocholanolone (19-NE). Pregnanediol (PD) and pregnanetriol (PT) were also measured as endogenous reference compounds to define the individual endogenous isotopic profile. Our results confirmed the impact of finasteride, especially if chronically administered, on the enzymatic pathway of testosterone and nandrolone, and pointed out the influence of 5-ARIs on delta C-13 values of the selected target compounds determined in the IRMS confirmation analysis.