Complementary stable carbon isotope ratio and amount of substance measurements in sports anti‐doping

Cawley, Adam; George, Adrian V.

doi:10.1002/dta.1378

Cited by 16 publications

(9 citation statements)

References 123 publications

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“…The fact that the 7β‐hydroxy‐isomer showed no visible alteration in the concentration (for both volunteers) does not agree with previous publications about 7‐keto‐DHEA metabolism . The results obtained by GC–MS/MS are supported by the measurements in GC‐TOF, and no explanation as was observed for the 7α‐isomer could be found.…”

Section: Resultscontrasting

confidence: 78%

7‐keto‐DHEAmetabolism in humans. Pitfalls in interpreting the analytical results in the antidoping field

Brito

Torre

Colamonici

et al. 2019

Drug Testing and Analysis

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7‐keto‐DHEA (3β‐hydroxy‐androst‐5‐ene‐7,17‐dione) is included in section S1 of the World Antidoping Agency (WADA) List of Prohibited Substances. The detection of its misuse in sports needs special attention, since it is naturally present in urine samples. The main goal of this study is to investigate the in vivo metabolism of 7‐keto‐DHEA after a single administration to healthy volunteers and to better describe the relationship between arimistane (androst‐5‐ene‐7,17‐dione) and 7‐keto‐DHEA after the application of the common routine procedures to detect anabolic steroids in WADA accredited antidoping laboratories. Free, glucuro‐, and sulpho‐conjugated steroids extracted from urine samples obtained before and after the administration of 7‐keto‐DHEA were analyzed by different gas chromatographic (GC)–mass spectrometric (MS) techniques. Gas chromatography coupled to tandem MS to study the effect on the endogenous steroid profile, coupled to isotope ratio mass spectrometry (IRMS) to investigate the potential formation of androgens derived from DHEA and coupled to high resolution accurate mass spectrometry (HRMS) to investigate new diagnostic metabolites. The analysis by IRMS confirmed that there is no formation of DHEA from 7‐keto‐DHEA. Ten proposed metabolites, not previously reported, were described. These include reduced and hydroxylated structures that are not considered part of the steroid profile in antidoping analyses. They showed considerable responses in all fractions analyzed. Some deoxidation reactions (including arimistane formation) were found and most probably can be linked to the sample preparation or instrumental analysis. This is important when interpreting the results after the application of procedures to detect steroids in urine currently used in antidoping laboratories. 7‐keto‐DHEA metabolism in humans for antidoping purposes was studied and unexpected results were found. This could lead to a misinterpretation of the data, depending on the procedure applied and the analytical instrumentation used.

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Section: Resultscontrasting

confidence: 78%

7‐keto‐DHEAmetabolism in humans. Pitfalls in interpreting the analytical results in the antidoping field

Brito

Torre

Colamonici

et al. 2019

Drug Testing and Analysis

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“…[1,2] Besides other parameters that have been identified and established in the so-called steroid profile to detect T or T prohormone applications, the main biomarker remains the urinary concentration ratio of T over epitestosterone (17α-hydroxy-androst-4-en-3-one, E), both excreted glucuronidated (GLUC). [1,2] Besides other parameters that have been identified and established in the so-called steroid profile to detect T or T prohormone applications, the main biomarker remains the urinary concentration ratio of T over epitestosterone (17α-hydroxy-androst-4-en-3-one, E), both excreted glucuronidated (GLUC).…”

Section: Introductionmentioning

confidence: 99%

Genotype‐dependent metabolism of exogenous testosterone – new biomarkers result in prolonged detectability

Piper

Schänzer

Thevis

2016

Drug Testing and Analysis

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Testosterone (T) misuse still represents a major problem in sports drug testing. Many strategies have been developed and applied to routine doping controls in recent years to enable both to identify suspicious samples in initial testing procedures and to confirm the exogenous origin of urinary T by means of carbon isotope ratio (CIR) determinations. Depending on the tested individual's genotype of UGT2B17, significantly different amounts of T are glucuronidated and excreted, which results in unaffected T/epitestosterone ratios after T misuse in those subjects with the deletion/deletion polymorphism (del/del). The aim of this study was to investigate differences in metabolic pathways of orally administered T between persons of del/del and insertion/insertion (ins/ins) genetic polymorphism. Therefore, a recently established method using hydrogen isotope ratios together with high-resolution and high-accuracy mass spectrometry was applied after administration of deuterated T to n = 4 subjects including both genotypes. Participants collected urine specimens directly before and for up to 8 days after the application. Urine aliquots were prepared to yield unconjugated, glucuronidated, and sulphoconjugated fractions of urinary steroids. Besides the significant difference in the excretion of T-glucuronide, all measured metabolites varied rather on an individual basis than due to a genotype difference. New T metabolites (both methylated and de-methylated) were detected and investigated regarding their potential to enhance the screening for T misuse. Sulphoconjugated epiandrosterone was further identified as the biomarker allowing for a prolonged retrospective detection of T misuse by means of CIR determinations for up to 5 days compared to 1 day if currently applied sports drug testing procedures were used. Copyright © 2016 John Wiley & Sons, Ltd.

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“…[129] Fürd ie quantitative LC-MS/MS-Analyse eines Analyten in einer komplexen Matrix (Blut, Urin, Gallensekret usw.) [136] Ebenso werden isotopenmarkierte,i nterne MS-Standards bei der Analyse von legalen und illegalen Drogen, [137] bei Antidopingtests, [138] fürd as Biomonitoring beim Menschen [139] und in großem Umfang in der Umweltanalytik, etwa in der Ökotoxikologie sowie der Luft- [140] und Grundwasseranalyse, [141] bençtigt. Sie kompensieren Matrixeffekte, [130] z.…”

Section: Isotopeneffekte Bei Nicht-kovalenten Wechselwirkungenunclassified

Deuterium‐ und tritiummarkierte Verbindungen: Anwendungen in den modernen Biowissenschaften

Atzrodt¹,

Derdau²,

Kerr

et al. 2018

Angewandte Chemie

108

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Wasserstoffisotope sind einzigartige Werkzeuge zur Identifizierung und Erforschung biologischer oder chemischer Vorgänge. Wasserstoffisotopenmarkierungen erlauben den spurlosen und direkten Einbau einer zusätzlichen Masseneinheit oder eines radioaktiven Markers in ein organisches Molekül, und dies praktisch ohne Änderungen der chemischen Struktur, der physikalischen Eigenschaften oder der biologischen Aktivität. Die Verwendung von deuteriummarkierten Isotopologen zur Untersuchung der spezifischen massenspektrometrischen (MS) Muster, die von Gemischen biologisch relevanter Moleküle hervorgerufen werden, ermöglicht eine drastische Vereinfachung der Analyse. Solche Methoden ermöglichen nun tiefe Einblicke in einen großen, kontinuierlich anwachsenden Bereich von Anwendungen in den Biowissenschaften und darüber hinaus. Speziell Tritium (3H) wird zunehmend eingesetzt, insbesondere in der pharmazeutischen Wirkstoffsuche. Aufwand und Kosten der Synthese markierter Verbindungen werden durch die hohe Empfindlichkeit der Analyse und hohe Zuverlässigkeit der erhaltenen Daten mehr als ausgeglichen. In diesem Aufsatz werden Fortschritte bei der Verwendung von Wasserstoffisotopen in den Biowissenschaften beschrieben.

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Complementary stable carbon isotope ratio and amount of substance measurements in sports anti‐doping

Cited by 16 publications

References 123 publications

7‐keto‐DHEAmetabolism in humans. Pitfalls in interpreting the analytical results in the antidoping field

7‐keto‐DHEAmetabolism in humans. Pitfalls in interpreting the analytical results in the antidoping field

Genotype‐dependent metabolism of exogenous testosterone – new biomarkers result in prolonged detectability

Deuterium‐ und tritiummarkierte Verbindungen: Anwendungen in den modernen Biowissenschaften

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