Drug-drug interactions and masking effects in sport doping: influence of miconazole administration on the urinary concentrations of endogenous anabolic steroids

Abstract

We have investigated the influence of oral\ud miconazole administration on the urinary concentrations of\ud endogenous anabolic androgenic steroids of doping relevance,\ud specifically considering all these compounds routinely monitored in doping control analysis, in the framework of the\ud steroidalmodule of the ‘‘athlete biologicalpassport’’, and other\ud steroids, including dehydroepiandrosterone, 5a-dihydrotestosterone, and the hydroxylated metabolites recently\ud proposed as additional markers of the intake of testosteronerelated steroids (16a-hydroxy-androsterone, 16a-hydroxyetiocholanolone, 6b-hydroxy-androsterone, 6b-hydroxy-etiocholanolone, 7a-hydroxy-dehydroepiandrosterone, and 7bhydroxy-dehydroepiandrosterone). Urinary concentrations of\ud the final metabolic products of the glucocorticoid biosynthetic\ud pathways (11b-hydroxy-androsterone and 11b-hydroxy-etiocholanolone, the formerly used as an endogenous reference\ud compound for the gas chromatography–combustion-isotope\ud ratio mass spectrometry confirmation analysis) were also\ud monitored. Two healthy Caucasian volunteers exhibiting\ud physiologically high testosterone/epitestosterone ratios and\ud elevated concentrations of the main target steroids were\ud selected for the study. Miconazole was administered orally\ud (500 mg/day) for 1 week. Multiple urine samples were\ud collected for 1 week before and during the treatment, and\ud analyzed according to a validated analytical procedure based\ud on gas chromatography–electron ionization-mass spectrometry in selected ion monitoring mode. Our results indicated that\ud oral administration of miconazole decreased the urinary concentrations of androsterone, and to a lesser extent, of etiocholanolone (both detected as the sum of free and glucuronated\ud steroids), and consequently the androsterone/testosterone and\ud androsterone/etiocholanolone ratios. Furthermore, the urinary\ud concentrations of 16a-hydroxy-etiocholanolone, 16a-hydroxy-androsterone, 7b-hydroxy-dehydroepiandrosterone,\ud 6b-hydroxy-etiocholanolone, 7a-hydroxy-dehydroepiandrosterone, 6b-hydroxy-androsterone, 11b-hydroxy-androsterone,\ud and 11b-hydroxy-etiocholanolone were significantly suppressed. This evidence suggests the potential intake of\ud miconazole whenever the urinary steroid profile is characterized by abnormally low concentrations of the above-mentioned steroids

Detection of urinary metabolites of arimistane in humans by gas chromatography coupled to high‐accuracy mass spectrometry for antidoping analyses

“…The steroid profile parameters monitored in ABP were determined following the procedure routinely used, and under the WADA and ISO17025 accreditation of our laboratory (Laboratorio Antidoping FMSI of Rome, Italy). The trimethylsilyl derivatives of the endogenous steroids in free plus glucuronated fraction in urine were measured …”

“…The data acquisition was performed in multiple reaction monitoring mode. This already published method is used for the determination of the steroid profile as defined in the WADA technical document TD2018EAAS, used routinely by the WADA accredited laboratory of Rome and under the ISO17025 scope of the same laboratory. The steroid profile included the quantitation of T, E, A, Etio, 5αAdiol and 5βAdiol, and the ratios T/E, A/Etio, A/T, 5αAdiol/5βAdiol and 5αAdiol/E.…”

Detection of 5α‐reductase inhibitors by UPLC–MS/MS: Application to the definition of the excretion profile of dutasteride in urine

“…According to WADA guidelines, the presence of dutasteride in urine samples collected during doping control tests has to be checked. For this reason, the possibility of including dutasteride in the analytical procedures (mainly based on the use of liquid/liquid extraction at controlled pH using TBME, or on the use of cation exchange cartridges) already in use in our WADA‐accredited laboratory was considered . In detail, the extraction protocol currently adopted by our laboratory to screen for more than 300 prohibited compounds by LC–MS was selected.…”

Drug–drug interaction and doping: Effect of non‐prohibited drugs on the urinary excretion profile of methandienone

“…The urine samples utilized in this study were from previous research carried out in our laboratory . [The administration studies were approved by the Local Ethical Committee (approval code: Prot.…”

“…In previous studies, by in vitro experiments carried out on human liver microsomes (HLM) and single CYP or uridine 5′‐diphospho‐glucuronosyl‐transferase (UGT) isoforms, we observed that the metabolic profile of other compounds included in the WADA prohibited list (ie, toremifene, stanozolol and 19‐nortestosterone) was extensively altered in the presence of both antifungals and antidepressants …”