Doping-control analysis of the 5alpha-reductase inhibitor finasteride: determination of its influence on urinary steroid profiles and detection of its major urinary metabolite.

摘要

5alpha-Reductase inhibitors such as finasteride are prohibited in sports according to the World Anti-Doping Agency. This class of drugs is used therapeutically to treat benign prostatic hyperplasia, as well as male baldness, by decreasing 5alpha-reductase activity. Accordingly, metabolic pathways of endogenous as well as synthetic steroids are influenced, which complicates the evaluation of steroid profiles in sports drug testing. The possibility of manipulating steroid excretion profiles and, presumably, to mask steroid abuse was investigated in 5 administration studies with use of finasteride at different doses, with and without coadministration of 19-norandrostenedione. The evaluation of urinary steroid profiles demonstrated the intense effect of finasteride on numerous crucial analytical parameters, in particular the production of 5alpha-steroids such as androsterone and 5alpha-androstane-3alpha,17beta-diol, which was significantly reduced. In addition, the excretion of the main metabolite of norandrostenedione, norandrosterone, was significantly suppressed, by up to 84%, in elimination studies. For doping-control analysis the use of 5alpha-reductase inhibitors causes considerable problems because steroid profile parameters, which are commonly considered stable, are highly affected and complicate the detection of steroid abuse. In addition, the suppression of production and renal excretion of 5alpha-steroids such as 19-norandrosterone generated from anabolic agents such as 19-norandrostenedione may lead to false-negative doping-control results, because urine specimens are reported positive only when a threshold level of 2 ng/mL is exceeded. Finally, a method for the determination of the major urinary metabolite of finasteride (carboxy-finasteride) in routine doping-control screening with use of liquid chromatography-tandem mass spectrometry is described, allowing the detection of carboxy-finasteride for up to 94 hours in urine specimens collected after an oral administration of 5 mg of finasteride.