Received for publication March 14, 2006.
Revised May 17, 2006.
Accepted for publication May 17, 2006.

Quantitative Determination of Metabolic Products of 19-Norandrostenediol in Human Plasma using Gas Chromatography / Mass Spectrometry

Abstract

Prohormones such as 19-norandrostenediol (estr-4-ene-3,17-diol) have been added to the list of prohibited substances of the World Anti-Doping Agency as 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 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 (GC/MS). 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 tables 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 as plasma concentrations of nandrolone between 0.3-1.2 ng/mL have been reported to influence endocrinological parameters.

Key words: analytical chemistry, drug disposition, mass spectrometry, steroids

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