Quantitative determination of metabolic products of 19-norandrostenediol in human plasma using gas chromatography/mass spectrometry

Prohormones were available as nutritional supplements for over-the-counter (OTC) sales in the United States until the commencement of the Anabolic Steroid Control Act of 2004. In 1999 nandrolone prohormones 19-norandrostenedione (estr-4-ene-3,17-dione) and 19-norandrostenediol (estr-4-ene-3ß,17ß-diol, NDiol) 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. In 2001 results of a pilot study dealing with the in vivo conversion of 19-norandrostenedione were published. But so far, no studies on the metabolism and in vivo conversion of 19-norandrostenediol have been reported, nor have quantified data on resulting plasma nandrolone levels. To investigate the in vivo biotransformation of NDiol, an evaluation of plasma levels of 19-norsteroids, in particular of unconjugated nandrolone, was performed within an open label crossover phase I-clinical trial with eight healthy male volunteers. To gain information if the route of administration affects the metabolic rate of the compound, NDiol was tested formulated as capsules as well as sublingual tablets. Volunteers administered a 100 mg NDiol capsule and a 25 mg sublingual tablet, respectively, separated by a period of at least two weeks. Blood samples (10 mL) were collected immediately before supplementation and at 10, 20, 30, 45, 60, 90 minutes, 2 h, 3 h, 4 h, 6 h, 8 h and 24 h after administration. 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). Verf.-Referat (gekürzt)