Premium
Detecting the misuse of 7‐oxo‐DHEA by means of carbon isotope ratio mass spectrometry in doping control analysis
Author(s) -
Piper Thomas,
Fusshöller Gregor,
Geyer Hans,
Toboc Ani,
Dănilă MădălinGeorge,
Thevis Mario
Publication year - 2020
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.8776
Subject(s) - chemistry , metabolite , isotope ratio mass spectrometry , urinary system , dehydroepiandrosterone , urine , mass spectrometry , chromatography , endocrinology , medicine , hormone , androgen , biochemistry
Rationale The misuse of 7‐oxo‐DHEA (3β‐hydroxyandrost‐5‐ene‐7,17‐dione) is prohibited according to the World Anti‐Doping Agency (WADA) code. Nevertheless, it is easily available as a dietary supplement and from black market sources. In two recent doping control samples, significant amounts of its main metabolite 7β‐OH‐DHEA were identified, necessitating further investigations. Methods As both 7‐oxo‐DHEA and 7β‐OH‐DHEA are endogenously produced steroids and no concentration thresholds applicable to routine doping controls exist, the development and validation of a carbon isotope ratio (CIR) mass spectrometry method ha been desirable. Excretion studies encompassing 7‐oxo‐DHEA, 7‐oxo‐DHEA‐acetate, and in‐house deuterated 7‐oxo‐DHEA were conducted and evaluated with regard to urinary CIR and potential new metabolites of 7‐oxo‐DHEA. Results Numerous urinary metabolites were identified, some of which have not been reported before, while others corroborate earlier findings on the metabolism of 7‐oxo‐DHEA. The CIRs of both 7‐oxo‐DHEA and 7β‐OH‐DHEA were significantly influenced for more than 50 h after a single oral dose of 100 mg, and a novel metabolite (5α‐androstane‐3β,7β‐diol‐17‐one) was found to prolong this detection time window by approximately 25 h. Applying the validated method to routine doping control specimens presenting atypically high urinary 7β‐OH‐DHEA levels clearly demonstrated the exogenous origin of 7‐oxo‐DHEA and 7β‐OH‐DHEA. Conclusions As established for other endogenously produced steroids such as testosterone, the CIR allows for a clear differentiation between endo‐ and exogenous sources of 7‐oxo‐DHEA and 7β‐OH‐DHEA. The novel metabolites detected after administration may help to improve the detection of 7‐oxo‐DHEA misuse and simplify its detection in doping control specimens.