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QUANTITATIVE DETERMINATION OF METABOLIC PRODUCTS OF 19-NORANDROSTENEDIOL IN HUMAN PLASMA USING GAS CHROMATOGRAPHY/MASS SPECTROMETRY

German Sport University Cologne, Institute of Biochemistry, Cologne, Germany

Prohormones such as 19-norandrostenediol (estr-4-ene-3ß,17ß-diol) have been added to the list of prohibited substances of the World Anti-Doping Agency because they are metabolized to the common nandrolone metabolites norandrosterone and noretiocholanolone. So far, no studies on the metabolism and in vivo conversion of 19-norandrostenediol after oral or sublingual administration have been reported nor have had quantified data on resulting plasma nandrolone levels. In the present study, an open-label crossover trial with eight healthy male volunteers was conducted. After application of capsules or sublingual tablets of 19-norandrostenediol plasma concentrations of 19-norandrostenediol, nandrolone as well as major metabolites (19-norandrosterone and 19-noretiocholanolone) were determined using a validated assay based on gas chromatography/mass spectrometry. The administration of 100-mg capsules of 19-norandrostenediol yielded maximum plasma total concentrations (i.e., conjugated plus unconjugated compounds) of 1.1 ng/ml (±0.7) for 19-norandrostenediol, 4.0 ng/ml (±2.6) for nandrolone, 154.8 ng/ml (±130.8) for 19-norandrosterone, and 37.7 ng/ml (±6.9) for 19-noretiocholanolone. The use of 25-mg sublingual tablets resulted in 3.3 ng/ml (±1.0) for 19-norandrostenediol, 11.0 ng/ml (±6.4) for nandrolone, 106.3 ng/ml (±40.1) for 19-norandrosterone, and 28.5 ng/ml (±20.8) for 19-noretiocholanolone. Most interestingly, the pharmacologically active unconjugated nandrolone was determined after administration of sublingual tablets (up to 5.7 ng/ml) in contrast to capsule applications. These results demonstrate the importance of prohibiting prohormones such as 19-norandrostenediol, in particular, since plasma concentrations of nandrolone between 0.3 to 1.2 ng/ml have been reported to influence endocrinological parameters.

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