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Detection of urinary metabolites of arimistane in humans by gas chromatography coupled to high-accuracy mass spectrometry for antidoping analyses.
Rapid Communications in Mass Spectrometry ( IF 2 ) Pub Date : 2019-12-30 , DOI: 10.1002/rcm.8529
Dayamin Martinez Brito 1 , Xavier de la Torre 1 , Francesco Botrè 1, 2
Affiliation  

RATIONALE The selection of the most appropriate metabolites of the substances included in the Prohibited List of the World Anti-Doping Agency (WADA) is fundamental for setting up methods allowing the detection of their intake by mass spectrometric methods. The aim of this work is to investigate the metabolism of arimistane (an aromatase inhibitor included in the WADA list) in order to improve its detection capacity among the antidoping community. METHODS Urinary samples collected after controlled single administration of arimistane in three healthy volunteers were analysed using the common routine sample preparation in antidoping laboratories to determine the steroid profile parameters considered in the steroid module of the Athlete Biological Passport by gas chromatography coupled to tandem mass spectrometry (GC/MS/MS). For the elucidation of the proposed metabolites, GC coupled to high-accuracy MS (GC/qTOFMS) was used. Both mass spectrometers were operated in electron ionization mode. Non-conjugated (free), glucuronated and sulfated fractions were analysed separately. RESULTS No relevant effects on the steroid profile could be detected after a single oral dose (25 mg). Up to 15 metabolites, present only in the post-administration samples, were detected and some structures were postulated. These metabolites are mainly excreted as glucuro-conjugated into urine and only minor amounts of two metabolites are also excreted unconjugated or as sulfates. CONCLUSIONS Arimistane itself was not observed in the free or glucuronated fractions, but only in the sulfate fraction. The peaks showing mass spectra in agreement with hydroxylated metabolites did not match with those for 7-keto-DHEA, 7α- or 7β-hydroxy-DHEA. This suggests that the first hydroxylation did not occur on C3, but on C2. These newly described metabolites allow the specific detection of arimistane misuse in sports.

中文翻译:

气相色谱与高精度质谱联用检测人体内阿里斯汀的尿代谢产物,以进行反掺杂分析。

理由选择世界反兴奋剂机构(WADA)禁用清单中所含物质的最合适代谢物是建立可通过质谱法检测其摄入量的方法的基础。这项工作的目的是研究arimistane(WADA列表中包括的一种芳香酶抑制剂)的代谢,以提高其在反兴奋剂界的检测能力。方法采用反兴奋剂实验室的常规常规样品制备方法,对三名健康志愿者进行单次控制的金刚烷烷单次给药后收集的尿液样品进行分析,以测定气相色谱-串联质谱法在运动员生物护照的类固醇模块中考虑的类固醇谱参数( GC / MS / MS)。为了阐明拟议的代谢物,使用了与高精度质谱联用的GC(GC / qTOFMS)。两种质谱仪均以电子电离模式运行。非结合的(游离的),葡萄糖醛酸化的和硫酸化的部分分别进行分析。结果单次口服剂量(25 mg)对类固醇激素没有相关影响。仅在给药后样品中最多检测到15种代谢物,并推测了一些结构。这些代谢物主要通过葡萄糖尿素共轭物排泄到尿液中,并且只有少量的两种代谢物也以非共轭物或硫酸盐的形式排泄。结论在游离或葡萄糖醛酸馏分中未观察到金刚烷本身,仅在硫酸盐馏分中观察到。质谱图中与羟基化代谢产物一致的峰与7-酮-DHEA,7α-或7β-羟基-DHEA的峰不匹配。这表明第一次羟基化不是发生在C3上,而是发生在C2上。这些新近描述的代谢物可以特异性检测出体育中对金刚烷滥用的情况。
更新日期:2019-11-21
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