Doping Control Research Group, Catalonian Antidoping Laboratory, Barcelona, Spain.
Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
Drug Test Anal. 2019 Mar;11(3):392-402. doi: 10.1002/dta.2529. Epub 2018 Nov 20.
The detection of testosterone (T) misuse is performed using the steroid profile that includes concentrations of T and related metabolites excreted free and glucuronoconjugated, and the ratios between them. In this work, the usefulness of 14 endogenous steroid sulfates to improve the detection capabilities of oral T administration has been evaluated. Quantitation of the sulfate metabolites was performed using solid-phase extraction and analysis by liquid chromatography-tandem mass spectrometry. Urine samples were collected up to 144 hours after a single oral dose of T undecanoate (120 mg) to five Caucasian male volunteers. Detection times (DTs) of each marker were estimated using reference limits based on a population study and also monitoring the individual threshold for each volunteer. High inter-individual variability was observed for sulfate metabolites and, therefore, better DTs were obtained using individual thresholds. Using individual threshold limits, epiandrosterone sulfate (epiA-S) improved the DT with respect to testosterone/epitestosterone (T/E) ratio in all volunteers. Androsterone, etiocholanolone, and two androstanediol sulfates also improved DTs for some volunteers. Principal component analysis was used to characterize the sample cohort, obtaining 13 ratios useful for discrimination. These ratios as well as the ratio epiA-S/dehydroepiandrosterone sulfate were further examined. The most promising results were obtained using ratios between sulfates of epiA, androsterone, or androstanediol 1 and E, and also sulfates of epiA or androstanediol 1, and dehydroandrosterone. These selected ratios prolonged the DT of oral T administration up to 144 hours, which corresponded to a significantly higher retrospectivity compared to those obtained using concentrations or the conventional T/E ratio.
睾酮（T）滥用的检测是通过类固醇谱来进行的，该谱包括 T 和相关代谢物的浓度，这些代谢物以游离形式和葡萄糖醛酸结合形式排泄，并评估了 14 种内源性类固醇硫酸盐在提高口服 T 给药检测能力方面的有用性。硫酸盐代谢物的定量使用固相萃取和液相色谱-串联质谱分析进行。对五名白种男性志愿者单次口服十一酸睾酮（120mg）后 144 小时内的尿液样本进行了收集。使用基于人群研究的参考限值和监测每个志愿者的个体阈值来估计每个标志物的检测时间（DT）。硫酸盐代谢物的个体间变异性很大，因此使用个体阈值可以获得更好的 DT。使用个体阈值限制，表雄酮硫酸盐（epiA-S）提高了所有志愿者中 T/E 比值的 DT。雄酮、表雄烷酮和两种雄烷二醇硫酸盐也提高了一些志愿者的 DT。主成分分析用于表征样本队列，获得了 13 个用于区分的有用比值。还进一步检查了这些比值以及 epiA-S/脱氢表雄酮硫酸盐的比值。使用 epiA、雄酮或雄烷二醇 1 和 E 的硫酸盐之间的比值以及 epiA 或雄烷二醇 1 和脱氢表雄酮的硫酸盐之间的比值得到了最有前途的结果。这些选定的比值将口服 T 给药的 DT 延长至 144 小时，与使用浓度或常规 T/E 比值相比，回溯时间显著延长。
