title: Development of criteria for the detection of adrenosterone administration by gas chromatography-mass spectrometry and gas chromatography-combustion-isotope ratio mass spectrometry for doping control.
abstract: Adrenosterone (androst-4-ene-3,11,17-trione, 11-oxoandrostenedione) is an endogenous steroid hormone that has been promoted as a dietary supplement capable of reducing body fat and increasing muscle mass. It is proposed that adrenosterone may function as an inhibitor of the 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11beta-HSD1), which is primarily responsible for reactivation of cortisol from cortisone. The urinary metabolism of adrenosterone was investigated, after a single oral administration in two male subjects, by gas chromatography-mass spectrometry (GC-MS) and gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Substantially increased excretion of 11beta-hydroxyandrosterone, 11beta-hydroxyetiocholanolone, 11-oxoandrosterone and 11-oxoetiocholanolone was observed. Minor metabolites such as 3alpha,17beta-dihydroxy-5beta-androstan-11-one, 3alpha-hydroxyandrost-4-ene-11,17-dione and 3alpha,11beta-dihydroxyandrost-4-en-17-one were also identified. The exogenous origin of the most abundant adrenosterone metabolites was confirmed by GC-C-IRMS according to World Anti-Doping Agency criteria. Through analysis of a reference population data set obtained from urine samples provided by elite athlete volunteers (n = 85), GC-MS doping control screening criteria are proposed: 11beta-hydroxyandrosterone concentration greater than 10 000 ng/mL (specific gravity adjusted to 1.020) or 11beta-hydroxyandrosterone/11beta-hydroxyetiocholanolone ratio greater than 20.Urine samples fulfilling these screening criteria may be subjected to GC-C-IRMS analysis for confirmation of adrenosterone administration.
authors.affiliation: Australian Sports Drug Testing Laboratory, National Measurement Institute, 1 Suakin Street, Pymble, NSW 2073, Australia.
authors.forename: Lance
authors.initials: L
authors.lastname: Brooker
authors.forename: Maria Kristina
authors.initials: MK
authors.lastname: Parr
authors.forename: Adam
authors.initials: A
authors.lastname: Cawley
authors.forename: Ulrich
authors.initials: U
authors.lastname: Flenker
authors.forename: Christopher
authors.initials: C
authors.lastname: Howe
authors.forename: Rymantas
authors.initials: R
authors.lastname: Kazlauskas
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Schänzer
authors.forename: Adrian
authors.initials: A
authors.lastname: George
mesh_terms: D000736:Androstenes / Q000493:pharmacokinetics / Q000592:standards* / Q000652:urine*; D056352:Athletes; D002247:Carbon Isotopes / Q000652:urine*; D019587:Dietary Supplements / Q000032:analysis; D004300:Doping in Sports; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D008297:Male; D012016:Reference Values; D013256:Steroids / Q000493:pharmacokinetics / Q000592:standards* / Q000652:urine*; D015813:Substance Abuse Detection / Q000379:methods* / Q000592:standards
chemical_list: D000736:Androstenes; D002247:Carbon Isotopes; D013256:Steroids; C011657:adrenosterone