1,720,968 research outputs found
The effect of the WADA list on the activity of the antidoping laboratories: reconsidering the “traditional” organization of the GC-MS screenings
No full textMicrowave-assisted Derivatization: Application to the Analysis of Diuretics and Corticosteroids
No full textParallel analysis of stimulants in saliva and urine by gas chromatography/mass spectrometry: perspectives for "in competition" anti-doping analysis.
No full textStimulants are banned by the World Anti-Doping Agency (WADA) if used “in competition”.
Being the analysis of stimulants presently carried out on urine samples only, it might
be useful, for a better interpretation of analytical data, to discriminate between an early
intake of the substance and an administration specifically aimed to improve the sport
performance. The purpose of the study was to investigate the differences, in terms of
excretion/disappearance of drugs, between urine and oral fluid, a sample that can reflect
plasmatic concentrations.
Oral fluid and urine samples were collected following oral administration of the following
stimulants: modafinil (100 mg), selegiline (10 mg), crotetamide/cropropamide (50mg
each), pentetrazol (100 mg), ephedrine (12 mg), sibutramine (10 mg), mate de coca (a dose
containing about 3mg of cocaine); analysis of drugs/metabolites was carried out by gas
chromatography/mass spectrometry (GC/MS) in both body fluids.
Our results showthat both the absolute concentrations and their variation as a function of
time, in urine and in oral fluid, are generally markedly different, being the drugs eliminated
from urinemuch more slowly than from oral fluid. Our results also suggest that the analysis
of oral fluid could be used to successfully complement the data obtained from urine for “in
competition” anti-doping tests; in all those cases in which the metabolite(s) concentration
of a substance in urine is very low and the parent compound is not detected, it is indeed
impossible, relying on urinary data only, to discriminate between recent administrations of
small doses and remote administrations of higher doses
Metabolism of formestane in humans: identification of urinary biomarkers for antidoping analysis
Full text linkFormestane (4-hydroxyandrost-4-ene-3,17-dione, 4OH-AED) is an aromatase inhibitor prohibited in sports. In recent years, it has been demonstrated that it can also originate endogenously by the hydroxylation in C4 position of androstenedione. Thus, the use of isotope ratio mass spectrometry (IRMS) is mandatory according to the World Antidoping Agency (WADA) to discriminate endogenous from synthetic origin. In a previous work and after oral administrations of formestane (4OH-AED), the ratio between the main formestane metabolite (4α-hydroxyepiandrosterone; 4OH-EA) and formestane parent compound could help to identify the endogenous origin, avoiding unnecessary and costly IRMS confirmations. In the present work, we investigated whether the same criteria could also be applied after transdermal applications. Six volunteers were transdermally treated once with formestane. Urine samples were collected for 120 h postadministration and analyzed by gas chromatography coupled to mass spectrometry (GC-MS and GC-MS/MS). Formestane and its major metabolites were monitored. The kinetic profile of formestane and its main metabolites was found different between oral and transdermal application. A shift on the excretion of the metabolites compared to formestane itself that can be observed after the oral administration, is absent after the transdermal one. This makes that a simple criteria cannot be applied to differentiate the endogenous from the synthetic origin based on metabolic ratios. The ratio between 4-hydroxyepiandrosterone and 4-hydroxyandrosterone (4OH-A) can be used to differentiate the route of administration. Ratios higher than one (4OH-EA/4OH-A > 1) are diagnostic of an oral administration. This allows to correctly interpret the 4OH-EA/4OH-AED ratio as proposed in our previous investigation. The results of this work demonstrate that the use of appropriate biomarkers (metabolic ratios) helps to reach correct conclusions without using complex and costly instrumentation approaches
Isotope ratio mass spectrometry in antidoping analysis: The use of endogenous reference compounds
Full text linkRationale: 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 13 C 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 13 C 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 13 C 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
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Detection of formestane abuse by mass spectrometric techniques.
No full textFormestane (4-hydroxy-androstenedione) is an aromatase inhibitor prohibited in sports and included, since 2004, in the list of prohibited substances updated yearly by the World Anti-Doping Agency (WADA). Since the endogenous production of formestane has been described, it is mandatory for the anti-doping laboratories to use isotope ratio mass spectrometry (IRMS) to establish the exogenous origin before issuing an adverse analytical finding. The described IRMS methods for formestane detection are time-consuming, requiring usually two consecutive liquid chromatographic sample purifications in order to have final extracts of adequate purity before the mass spectrometric analysis. After establishing a procedure for the determination of the origin of formestane by IRMS without the need of derivatization, and integrated in the overall analytical strategy of the laboratory for pseudo-endogenous steroids, a mass spectrometric analysis by gas chromatography-mass spectrometry (GC-MS) and gas chromatography-tandem mass spectrometry (GC-MS/MS) of formestane metabolites was carried out in order to investigate whether other biomarkers of formestane abuse could be integrated in order to avoid time-consuming and expensive IRMS confirmations for formestane. From the metabolic studies performed, the inclusion of 3β,4α-dihydroxy-5α-androstan-17-one (4α-hydroxy-epiandosterone) in the routine GC-MS procedures has demonstrated to be diagnostic in order to reduce the number of unnecessary confirmations of the endogenous origin of formestane
Optimizing the cost/benefit ratio of the laboratory procedures: a way to match the WADA requirements (with the help of microwaves).
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