Gessner Lina, Thevis Mario, Rothschild Markus Alexander, Jübner Martin
Department of Toxicology, Institute of Legal Medicine, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany.
Center for Preventive Doping Research/Institute of Biochemistry, German Sport University Cologne, Cologne, Germany.
Drug Test Anal. 2022 Oct;14(10):1744-1761. doi: 10.1002/dta.3355. Epub 2022 Sep 2.
Situations of both, intentional and inadvertent or accidental doping, necessitate consideration in today's doping controls, especially in the light of the substantial consequences that athletes are facing in case of so-called adverse analytical findings. The aim of this study was to investigate, whether a transdermal uptake of doping substances would be possible. In addition to the period of detectability of the particular substances or respective characteristic metabolites, the possibility of deducing the route of administration by metabolite patterns was also assessed. Twelve male subjects were included in the study. Four common anabolic androgenic steroids (AAS) were dissolved in dimethylsulfoxide to facilitate transdermal administration on different skin regions. One half of the test persons received only oxandrolone (17α-methyl-2-oxa-4,5α-dihydrotestosterone), and the other half were applied a mixture of oxandrolone, metandienone (17β-hydroxy-17α-methylandrosta-1,4-dien-3-one), clostebol (4-chlorotestosterone-17β-acetate) and dehydrochloromethyltestosterone (DHCMT). Urine samples were collected 1 h, 6 h and one sample per day for the next 14 consecutive days. Measurements were conducted on a tandem-gas chromatography-mass spectrometry (GC-MS/MS) or tandem-liquid chromatography-MS/MS (LC-MS/MS) system. Substance findings were obtained at least 1 day after application on nearly all skin locations. The results indicated inter-individual variability in detection windows, also varying between the different analytes and possible impact of skin location and skin thickness, respectively. Nevertheless, a rapid and rather long detectability of all substances (or respective metabolites) was given, in some cases within hours after administration and for up to 10-14 days. Hence, the transdermal application or exposure to the investigated AAS is a plausible scenario that warrants consideration in anti-doping.
在当今的兴奋剂检测中，有意、无意或意外使用兴奋剂的情况都需要加以考虑，尤其是鉴于运动员在所谓的不利分析结果面前所面临的重大后果。本研究的目的是调查是否有可能通过皮肤吸收兴奋剂。除了特定物质或各自特征性代谢物的可检测期外，还评估了根据代谢物模式推断给药途径的可能性。12名男性受试者参与了该研究。将四种常见的合成代谢雄激素类固醇（AAS）溶解在二甲基亚砜中，以便在不同皮肤区域进行经皮给药。一半的测试者仅接受氧雄龙（17α-甲基-2-氧杂-4,5α-二氢睾酮），另一半则使用氧雄龙、美雄酮（17β-羟基-17α-甲基雄甾-1,4-二烯-3-酮）、氯睾酮（4-氯睾酮-17β-乙酸酯）和脱氢氯甲基睾酮（DHCMT）的混合物。在1小时、6小时时收集尿液样本，并在接下来连续14天每天收集一个样本。测量在串联气相色谱-质谱联用仪（GC-MS/MS）或串联液相色谱-质谱联用仪（LC-MS/MS）系统上进行。几乎在所有皮肤部位给药后至少1天就检测到了相关物质。结果表明，检测窗口存在个体差异，不同分析物之间也有所不同，并且分别受到皮肤部位和皮肤厚度的可能影响。尽管如此，所有物质（或各自的代谢物）都具有快速且相当长时间的可检测性，在某些情况下，给药后数小时内即可检测到，最长可达10 - 14天。因此，经皮应用或接触所研究的AAS是一种合理的情况，在反兴奋剂工作中值得考虑。
