Development of a GC/C/IRMS method – Confirmation of a novel steroid profiling approach in doping control

Renterghem, Pieter Van; Polet, Michaël; Brooker, Lance; Gansbeke, Wim Van; Eenoo, Peter Van

doi:10.1016/j.steroids.2012.05.009

Cited by 25 publications

(23 citation statements)

References 29 publications

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“…The results show that it was also one of the 5α‐metabolites, namely 5αAdiol, that was the best target compound for T gel detection by IRMS. This is in agreement with other studies investigating detectability of T gel by IRMS in healthy individuals, where primarily 5αAdiol and then T were shown to be the most sensitive target compounds (TC) . In contrast, we have shown that when administrating T through injection 5βAdiol as well as T were the best TCs for IRMS analysis …”

Section: Discussionsupporting

confidence: 92%

Sensitivity of doping biomarkers after administration of a single dose testosterone gel

Mullen

Börjesson

Hopcraft

et al. 2017

Drug Testing and Analysis

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Micro-doping with testosterone (T) is challenging to detect with the current doping tests. Today, the methods available to detect T are longitudinally monitoring of urine biomarkers in the Athlete Biological Passport (ABP) and measuring the isotopic composition of excreted biomarkers to distinguish the origin of the molecule. In this study, we investigated the detectability of a single dose of 100 mg T gel in 8 healthy male subjects. We also studied which biomarkers were most sensitive to T gel administration, including blood biomarkers. The ABP successfully detected T gel administration in all 8 subjects. The most sensitive ratio was 5αAdiol/E, however, all ratios showed atypical findings. Isotope ratio mass spectrometry (IRMS) was performed on 5 subjects and only 2 met all the criteria for a positive test according to the rules set by the World Anti-Doping Agency (WADA). The other 3 showed inconclusive results. Other markers that were affected by T gel administration, not used for this detection today, were serum dihydrotestosterone (DHT) and T as well as reticulocyte count and percentage in whole blood. miRNA-122 was not significantly affected by the single T dose. A single dose of 100 mg T gel is possible to detect with today's doping tests. Since a single dose of T gel has an impact on some hematological biomarkers, access to both modules of the ABP when evaluating the athletes' profiles will increase the possibility to detect micro-doses of T. In addition, serum DHT and T may be a useful addition to the future endocrine module of the ABP.

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Section: Discussionsupporting

confidence: 92%

Sensitivity of doping biomarkers after administration of a single dose testosterone gel

Mullen

Börjesson

Hopcraft

et al. 2017

Drug Testing and Analysis

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“…An aliquot of each urine sample was prepared to check the steroid profile according to routine sample preparation procedures (Van Eenoo et al ., ; De Brabanter et al ., ). The concentrations of the target compounds allowed us to calculate the necessary sample volume using the formula presented in previous work (Van Renterghem et al ., in press). This calculation was based upon a minimum final extract volume of 25 μL and a required extract concentration of 50 µg/mL, assuming 100% extraction recovery.…”

Section: Methodsmentioning

confidence: 97%

Development of a sensitive GC‐C‐IRMS method for the analysis of androgens

Polet

Gansbeke

Deventer

et al. 2012

Biomedical Chromatography

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The administration of anabolic steroids is one of the most important issues in doping control and is detectable through a change in the carbon isotopic composition of testosterone and/or its metabolites. Gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS), however, remains a very laborious and expensive technique and substantial amounts of urine are needed to meet the sensitivity requirements of the IRMS. This can be problematic because only a limited amount of urine is available for anti-doping analysis on a broad spectrum of substances. In this work we introduce a new type of injection that increases the sensitivity of GC-C-IRMS by a factor of 13 and reduces the limit of detection, simply by using solvent vent injections instead of splitless injection. This drastically reduces the amount of urine required. On top of that, by only changing the injection technique, the detection parameters of the IRMS are not affected and there is no loss in linearity.

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“…[26] Correction for acetate adducts The GC conditions were exactly the same as those described for full-scan GC-MS analysis.…”

Section: Gc-c-irmsmentioning

confidence: 99%

Studies on the minor metabolite 6a‐hydroxy‐androstenedione for doping control purposes and its contribution to the steroid profile

Polet

Renterghem

Gansbeke

et al. 2014

Drug Testing and Analysis

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Recent publications have shown that the concentrations of minor metabolites such as formestane and 6a-hydroxy-androstenedione (6aOHADION) are import parameters, capable of increasing the specificity and efficiency of steroid abuse screening. The importance of such minor metabolites has been recognized for some time, but setting up concentration thresholds is not that straightforward with a single quadrupole gas chromatograph mass spectrometer (GC-MS) because of the low concentrations; this is especially the case for 6aOH-ADION. The main aim of this study was to propose a concentration threshold above which the detected 6aOH-ADION is considered suspicious and isotope ratio mass spectrometry (IRMS) is recommended. Routine doping control samples (2128) from athletes that entered our lab and were not found suspicious for the intake of any doping substance were used to determine the baseline concentrations of 6a-OH-ADION. For this purpose, the more sensitive gas chromatography-tandem mass spectrometry (GC-MS/MS) was used, capable of quantifying these low concentrations with high reliability. A urinary concentration threshold of 5 ng/mL was set. Concentrations above this threshold are considered suspicious and are forwarded to IRMS for confirmation in routine practice. In addition, an IRMS method was developed, capable of determining the 13C value of 6aOH-ADION. If a urine sample has an elevated 6aOH-ADION concentration and normal 13C values for the traditional IRMS target compounds, we are still able to check the 13C value of 6aOH-ADION. Six excretion studies were executed to stress the applicability of the threshold by visualizing the concentration and δ13C value time profiles of 6aOH-ADION.

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Development of a GC/C/IRMS method – Confirmation of a novel steroid profiling approach in doping control

Cited by 25 publications

References 29 publications

Sensitivity of doping biomarkers after administration of a single dose testosterone gel

Sensitivity of doping biomarkers after administration of a single dose testosterone gel

Development of a sensitive GC‐C‐IRMS method for the analysis of androgens

Studies on the minor metabolite 6a‐hydroxy‐androstenedione for doping control purposes and its contribution to the steroid profile

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