Longitudinal evaluation of the isotope ratio mass spectrometric data: towards the ‘isotopic module’ of the athlete biological passport?

Jardines, Daniel; Botrè, Francesco; Colamonici, Cristiana; Curcio, Davide; Procida, Gemma; Torre, Xavier de la

doi:10.1002/dta.2118

Cited by 11 publications

(24 citation statements)

References 24 publications

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“…Additionally, based on abnormal values or profiles, athletes can be targeted for traditional anti‐doping tests to detect prohibited substances or methods. Although the ABP was initially proposed to monitor haematological variables to primarily detect blood doping (haematological module), this approach will be also used to detect the misuse of growth factors and anabolic steroids . At present, the ABP is a key tool for carrying out target testing, especially in endurance sports disciplines .…”

Section: Athlete Biological Passportmentioning

confidence: 99%

Thirteen years of the fight against doping in figures

Aguilar

Muñoz‐Guerra²,

Plata³

et al. 2017

Drug Testing and Analysis

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Every year, the World Anti-Doping Agency (WADA) publishes the main statistics reported by the accredited laboratories, which provide very valuable information for assessing changes in the patterns of doping in sports over time. Using the information provided since 2003 as the basis for the analysis, the evolution of doping/anti-doping figures over the last decade can be examined in reasonable detail, at least in reference to samples analyzed and categories of substances more commonly found in athletes' samples. This brief analysis of the WADA statistical reports leads us to the following outcomes: the increase in anti-doping pressure from 2003 to 2015, as evidenced by increased numbers of samples analyzed and banned substances, has not directly produced a higher frequency of adverse/atypical findings. Although this could be interpreted as steady state in the capacity to detect doping through this whole period, it also resulted in a significant increase in the absolute number of samples catalogued as doping (from 2247 in 2003 to 5912 in 2015). Anabolic agents have been the most common doping substances detected in all statistics reports while the remaining groups of substances are much less frequently found in doping control samples. Given that one might have expected the enhancement of the anti-doping programme led by WADA over this last decade to have increased the percentage of adverse/atypical findings, the fact that it did not might indicate the need to take another step in sampling strategies, such as 'more intelligent testing' based on the differences in the prevalence of doping substances among sports. Copyright © 2017 John Wiley & Sons, Ltd.

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Section: Athlete Biological Passportmentioning

confidence: 99%

Thirteen years of the fight against doping in figures

Aguilar

Muñoz‐Guerra²,

Plata³

et al. 2017

Drug Testing and Analysis

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“…[17] In other words, our confirmation capacity in much better than our capacity to detect suspicious samples at the screening level. In addition, recent studies have demonstrated that the delta values of a single individual have a much lower variability compared to the current parameters of the ABP, and that the evaluation of the absolute delta values or the delta-delta values relative to an ERC may improve the detection capacity of the method since the acceptance limits would be almost half of the current population based ones.…”

Section: Resultsmentioning

confidence: 98%

“…[17] If this is applied, this could eventually detect those synthetic preparations with delta values close to the endogenous values region. [18] To do so, the throughput of the current IRMS strategy must be improved, permitting the application of IRMS on a larger scale.…”

Section: Introductionmentioning

confidence: 99%

Fast IRMS screening of pseudoendogenous steroids in doping analyses

Torre

Colamonici

Curcio

et al. 2017

Drug Testing and Analysis

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The detection of the abuse of pseudoendogenous steroids (testosterone and/or its precursors) is currently based, when possible, on the application of the steroid module of the World Anti-Doping Agency (WADA), athlete biological passport (ABP), implemented through the global database, ADAMS. When a suspicious sample is detected, the confirmation by isotope ratio mass spectrometry (IRMS) is required. It is well known that this confirmation procedure is time consuming and expensive and can be only applied on a reduced number of samples. In previous studies we have demonstrated that the longitudinal evaluation of the IRMS data is able to detect positive samples that otherwise will be evaluated as negative, improving the efficacy of the fight against doping in sport. This would require the analysis of a much larger volume of samples by IRMS. The aim of the present work is to describe an IRMS screening method allowing to increase the throughput of samples that can be analyzed by IRMS. The detection efficacy of the method is compared with the confirmation method in use, and to assess its robustness and applicability, all the samples of a major cycling stage competition were analyzed, with the agreement of the testing authority, under routine conditions and response times. The results obtained permit to conclude that the IRMS screening method here proposed has adequate selectivity and produces results that overlap with the already validated method currently in use permitting to analyze a much higher volume of samples even during a major event without compromising the detection capacity.

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“…The stability of the delta values of the pseudoendogenous steroids, including the ERC necessary for their evaluation, could also be assessed if an evaluation of the delta values was made longitudinally as part of a module of the Athlete Biological Passport (ABP) as we suggested recently …”

Section: Discussionmentioning

confidence: 99%

Isotope ratio mass spectrometry in antidoping analysis: The use of endogenous reference compounds

Torre

Jardines

Curcio

et al. 2019

Rapid Comm Mass Spectrometry

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Rationale Isotope ratio mass spectrometry (IRMS) is an analytical technique required by the World Antidoping Agency (WADA) before releasing of an adverse finding for the abuse of pseudoendogenous steroids (i.e. testosterone). For every single individual, the delta 13C values (‰) of the selected target compounds (TCs, i.e. testosterone and/or its precursors/metabolites) are compared with those of endogenous reference compounds (ERCs). The aim of this work is to investigate the individual variation in the delta values of four different commonly used ERCs to establish the maximum acceptable variation, in order to detect potential outliers. Methods Routine urine samples collected for antidoping purposes were submitted to IRMS confirmation. After a specific liquid chromatographic purification of the analytes of interest, the final extracts were analyzed by gas chromatography/combustion (GC/C)‐IRMS. The selected ERCs monitored were pregnanediol, pregnanetriol, 11‐keto‐etiocholanolone and 11β‐hydroxyandrosterone. The obtained 13C delta values were statistically analyzed to evaluate their inter‐ and intra‐individual distribution. Results The delta values of the ERCs studied showed a normal distribution and no major differences among genders were observed. As expected, there are differences depending on the geographical origin of the samples, reflecting different dietary habits and food sources. The intra‐individual dispersion, expressed as the standard deviation (SD) of the values of the studied ERCs, did not greatly exceed the instrumental error (0.5‰), demonstrating the good preservation of the delta values along the metabolic pathway. Conclusions For the selected ERCs of non‐sporting volunteers and the urinary specimens from more than 1000 sportsmen, we can propose a maximum SD of 0.54‰ and range of 1.2‰ for delta 13C values as acceptance criteria to detect potential outliers. These cases can be caused by the external masking effect of the administration of a substance modifying the delta values or outliers due to unforeseen procedural artifacts.

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Longitudinal evaluation of the isotope ratio mass spectrometric data: towards the ‘isotopic module’ of the athlete biological passport?

Cited by 11 publications

References 24 publications

Thirteen years of the fight against doping in figures

Thirteen years of the fight against doping in figures

Fast IRMS screening of pseudoendogenous steroids in doping analyses

Isotope ratio mass spectrometry in antidoping analysis: The use of endogenous reference compounds

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