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.

中文翻译：

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在掺杂控制分析中通过碳同位素比率质谱法检测7-氧-DHEA的滥用。

理由根据世界反兴奋剂机构（WADA）的规定，禁止滥用7-氧代-DHEA（3β-羟基和5--5-烯-7,17-二酮）。然而，它很容易从膳食和黑市中获得。在两个最近的掺杂对照样品中，鉴定出大量的主要代谢物7β-OH-DHEA，因此有必要进行进一步研究。方法由于7-氧代-DHEA和7β-OH-DHEA都是内源性类固醇，并且不存在适用于常规掺杂控制的浓度阈值，因此需要开发和验证碳同位素比（CIR）质谱法。进行了包括7-氧代-DHEA，7-氧代-DHEA-乙酸盐和内部氘代7-氧代-DHEA的排泄研究，并对尿液CIR和7-氧代-DHEA的潜在新代谢产物进行了评估。结果鉴定出许多尿代谢产物，其中一些以前未曾报道过，而另一些证实了7-氧代-DHEA代谢的早期发现。单次口服100 mg和一种新的代谢产物（5α-androstane-3β，7β-diol-17-one）后，超过7 h的7-oxo-DHEA和7β-OH-DHEA的CIR均受到显着影响。发现）可将此检测时间窗口延长约25小时。将经过验证的方法应用于表现出非典型尿液中高水平7β-OH-DHEA的常规掺杂对照标本中，可以清楚地证明7-oxo-DHEA和7β-OH-DHEA的外源性来源。结论正如针对其他内源性类固醇（例如睾丸激素）的建立一样，CIR可以使7-氧代-DHEA和7β-OH-DHEA的内源性和外源性源之间有明显的区别。