Population based evaluation of a multi-parametric steroid profiling on administered endogenous steroids in single low dose

Renterghem, Pieter Van; Eenoo, Peter Van; Delbeke, Frans

doi:10.1016/j.steroids.2010.06.013

Cited by 40 publications

(76 citation statements)

References 26 publications

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“…In our study, eight ratios between either the 6OH-Andros3G or 6OH-Etio3G and TG, EG, AndrosG and EtioG as well as the 6OH-Andros3G/6OH-Etio3G were After the oral administration of T undecanoate, TG/EG gave DWs for the detection of T that were between 12 h to 48 h for volunteers 1, 2, 4 and 5 ( Table 2). As expected, these DWs were greater than previously reported detection times based on population reference limits [14,34]. However, they can be considered within the expected ranges of detection when individual limits are used.…”

Section: Discussionsupporting

confidence: 69%

Evaluation of two glucuronides resistant to enzymatic hydrolysis as markers of testosterone oral administration

Kotronoulas

Gómez-Gómez

Segura

et al. 2017

The Journal of Steroid Biochemistry and Molecular Biology

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Testosterone (T) has traditionally been the most commonly reported doping agent by doping control laboratories. The screening of T misuse is performed by the quantification of six endogenous androgenic steroids and the ratio T/E included in the Athlete Biological Passport (ABP). The inclusion of additional metabolites can improve the screening capabilities of ABP. In this study, the potential of 3α-glucuronide-6β-hydroxyandrosterone (6OH-Andros3G) and 3α-glucuronide-6β-hydroxyetiocholanolone (6OH-Etio3G) as markers of T oral administration was evaluated. These glucuronides have been shown to be resistant to enzymatic hydrolysis and their quantification by means of liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was reported as the only way to obtain feasible results. Urine samples were collected from five volunteers before and after the oral administration of 40mg of T undecanoate and were analyzed by a LC-MS/MS method recently developed. Concentration of 6OH-Andros3G and 6OH-Etio3G compounds and those of the glucuronides of T (TG), epitestosterone (EG), androsterone and etiocholanolone were established and different concentration ratios were calculated. The detection windows (DWs) for the T administration obtained by each selected ratio were compared to the one of TG/EG. The results showed that four out of the nine tested markers presented DWs much larger for all volunteers than those obtained by the World Anti-Doping Agency established T/E marker or other alternative markers. The 6OH-Andros3G/EG, 6OH-Etio3G/EG, 6OH-Andros3G/TG and 6OH-Etio3G/TG markers were able to identify the T abuse up to 96h after the administration, extending our detection capability for the misuse up to 84h more than the classic marker. The importance of these markers was also highlighted by their prolonged capacity to detect the T misuse in the case of one volunteer whose TG/EG barely exceeded his individual threshold. As a consequence, the four markers presented in this study seem to have an exceptional potential as biomarkers of T oral administration.

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Section: Discussionsupporting

confidence: 69%

Evaluation of two glucuronides resistant to enzymatic hydrolysis as markers of testosterone oral administration

Kotronoulas

Gómez-Gómez

Segura

et al. 2017

The Journal of Steroid Biochemistry and Molecular Biology

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“…Collected data belonging to the same athlete are then integrated in a Bayesian algorithm that allows for the determination of physiological ranges tailored for each individual, drastically reducing the risk of false atypical analytical findings and improving the overall detection capacity of the anti-doping system [24]. In addition to this approach, several researchers have proposed to consider also other specific hydroxylated/oxydized metabolites of EAASs [25][26][27][28], with the aim of both obtaining supplementary information about the compound administered and extending its detection window in urine. In particular, physiological urinary concentrations of most of these EAAS metabolites (also formed in biotransformations involving cytochrome P450 enzymes, including CYP3A4 and CYP2C9 [29]) are normally low [30].…”

Section: Introductionmentioning

confidence: 99%

“…In particular, physiological urinary concentrations of most of these EAAS metabolites (also formed in biotransformations involving cytochrome P450 enzymes, including CYP3A4 and CYP2C9 [29]) are normally low [30]. In this regard, it has been reported that after the intake of either dehydroepiandrosterone (DHEA), T and/or its precursors, it is possible to observe a characteristic increase in the urinary levels of 7a/b-hydroxy(OH)-DHEA, 16a/b-OH-DHEA, 7-keto-DHEA, 3a,5-cyclo-5a-androstan-6b-ol-17-one, 7-keto-Andro, 6a-OH-androstenedione (ASD), 6b-OHAndro, 6b-OH-Etio, 6b-OH-epiandrosterone(EA), 16a-OH-Andro, 16a-OH-Etio, 16a-OH-ASD, 4-OH-ASD, 4-OH-T, and 6-OH-T [25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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

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“…Despite the fact of being resistant to enzymatic hydrolysis, basal levels of 6OH-Andros and 6OH-Etio have been reported by methods involving a hydrolysis step [12,13]. In addition, contrarily to the results obtained by the detection of the intact glucuronides, a previous study established that their concentrations remain unchanged after the administration of T [14]. In the latter cases, the results were obtained after the use of the gas chromatography-mass spectrometry (GCeMS) procedure required by World Anti-Doping Agency (WADA) for the quantification of steroids.…”

Section: Introductionmentioning

confidence: 99%

Ultra high performance liquid chromatography tandem mass spectrometric detection of glucuronides resistant to enzymatic hydrolysis: Implications to doping control analysis

Kotronoulas

Marcos

Segura

et al. 2015

Analytica Chimica Acta

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Population based evaluation of a multi-parametric steroid profiling on administered endogenous steroids in single low dose

Cited by 40 publications

References 26 publications

Evaluation of two glucuronides resistant to enzymatic hydrolysis as markers of testosterone oral administration

Evaluation of two glucuronides resistant to enzymatic hydrolysis as markers of testosterone oral administration

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

Ultra high performance liquid chromatography tandem mass spectrometric detection of glucuronides resistant to enzymatic hydrolysis: Implications to doping control analysis

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