title: The detection of androstenedione abuse in sport: a mass spectrometry strategy to identify the 4-hydroxyandrostenedione metabolite.
abstract: Studies have shown that the administration of androstenedione (ADIONE) significantly increases the urinary ratio of testosterone glucuronide to epitestosterone glucuronide (T/E) - measured by gas chromatography/mass spectrometry (GC/MS) - in subjects with a normal ( approximately 1) or naturally high (>1) initial values. However, the urinary T/E ratio has been shown not to increase in subjects with naturally low (<1) initial values. Such cases then rely on the detection of C(6)-hydroxylated metabolites shown to be indicative of ADIONE administration. While these markers may be measured in the routine GC/MS steroid profile, their relatively low urinary excretion limits the use of gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) to specifically confirm ADIONE administration based on depleted (13)C content. A mass spectrometry strategy was used in this study to identify metabolites of ADIONE with the potential to provide compound-specific detection. C(4)-hydroxylation was subsequently shown to be a major metabolic pathway following ADIONE administration, thereby resulting in urinary excretion of 4-hydroxyandrostenedione (4OH-ADIONE). Complementary analysis of 4OH-ADIONE by GC/MS and GC/C/IRMS was used to confirm ADIONE administration.
authors.affiliation: Australian Sports Drug Testing Laboratory (ASDTL), National Measurement Institute (NMI), Pymble NSW 2073, Australia. Adam.Cawley@measurement.gov.au
authors.forename: Adam T
authors.initials: AT
authors.lastname: Cawley
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Trout
authors.forename: Rymantas
authors.initials: R
authors.lastname: Kazlauskas
authors.forename: Adrian V
authors.initials: AV
authors.lastname: George
mesh_terms: D000328:Adult; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000652:urine*; D002849:Chromatography, Gas / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D004300:Doping in Sports; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013055:Spectrophotometry, Infrared; D015813:Substance Abuse Detection / Q000379:methods*; D055815:Young Adult
chemical_list: D000735:Androstenedione; C014594:formestane