Isotopic fractionation of endogenous anabolic androgenic steroids and its relationship to doping control in sports

The use of gas chromatography (GC)-combustion (C)-isotope ratio mass spectrometry (IRMS) demonstrates that a single oral administration of dehydroepiandrosterone (DHEA, 100 mg) to a male subject significantly lowers the 13C content of etiocholanolone (Et) and androsterone (A) in the subject's urine. The difference in carbon isotope ratio (δ 13C‰) values between Et and A increases from 1.6‰ at the time of administration to 5.1‰ at 26 h post-administration, indicating preferential metabolism of administered DHEA to form Et in relation to A. Multiple oral administrations of DHEA to a male subject reveals lower δ13C values during the excretion period of Et (-31.7‰ to -34.6‰) and A (-31.4‰ to -33.0‰) to that of the δ13C value of the administered DHEA (-31.3‰). Reference distributions of δ13C Et and δ13C A constructed from normal athlete populations within Australia and New Zealand show a small natural discrimination against 13C in the formation of Et relative to A (mean = 0.3‰, n = 167, p = 0.007). Amplified differences between δ13C Et and δ13C A, and in vivo 13C depletion measured by GC-C-IRMS are shown to be potentially useful for doping control.