Profiling of urinary formestane and confirmation by isotope ratio mass spectrometry.
Formestane (F, androst-4-en-4-ol-3,17-dione) is an irreversible aromatase inhibitor with the ability to suppress the estrogen production from anabolic steroids. Consequently, F is mentioned on the World Anti-Doping Agency (WADA) prohibited list and because studies have shown that F is produced endogenously in small amounts, a threshold for urinary excreted F of 150 ng/mL was introduced. Lower concentrations could be due to endogenous production and need further investigation to prove the exact origin through determination of the carbon isotope ratio. However, because the current screening methods are a lot more sensitive, F is detected in practically every urine sample. A strict implementation of this WADA rule would imply that almost every urine sample needs additional investigation to verify an exogenous or endogenous origin. The main aim of this study was to propose and introduce a lower concentration limit of 25 ng/mL beneath which the detected F is considered as being endogenous and no further investigation is needed. The data presented in this paper suggests that this threshold provides a good balance between a sufficiently large detection window and not having to perform isotope ratio mass spectrometry (IRMS) analyses on negative urine samples.
Ghent University, Department of Clinical Chemistry, Microbiology and Immunology, Doping Control Laboratory, Technologiepark 30 B, B-9052 Zwijnaarde, Belgium. Electronic address: michael.polet@UGent.be.
Michael
M
Polet
Pieter
P
Van Renterghem
Wim
W
Van Gansbeke
Peter
P
Van Eenoo
D000328:Adult; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000652:urine; D002247:Carbon Isotopes / Q000737:chemistry; D004300:Doping in Sports / Q000517:prevention & control; D005260:Female; D006801:Humans; D057230:Limit of Detection; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D015203:Reproducibility of Results; D016482:Urinalysis / Q000379:methods*; D055815:Young Adult
D002247:Carbon Isotopes; D000735:Androstenedione; C014594:formestane
Doping control; Formestane; GC–C-IRMS; Steroid profiling