Mass spectrometry in sports drug testing: Structure characterization and analytical assays

Thevis, Mario; Schänzer, Wilhelm

doi:10.1002/mas.20107

Cited by 176 publications

(141 citation statements)

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“…As can be seen in Table 2, the accurate mass measurements for these two peaks (109.0648 and 97.0644) corresponded to the formulas C 7 H 9 O and C 6 H 9 O, respectively (mass errors less than 1 mDa). These ions are characteristic for 3-oxo-4-ene anabolic steroids and have been described for several related compounds (Williams et al, 1999;Thevis and Schänzer, 2007).…”

Section: Resultsmentioning

confidence: 70%

Detection and Characterization of a New Metabolite of 17α-Methyltestosterone

Pozo¹,

Eenoo²,

Deventer³

et al. 2009

Drug Metab Dispos

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ABSTRACT:The misuse of the anabolic steroid methyltestosterone is currently routinely monitored in doping control laboratories by gas chromatography-mass spectrometry (GC-MS) of two of its metabolites: 17␣-methyl-5␤-androstane-3␣,17␤-diol and 17␣-methyl-5␣-androstane-3␣,17␤-diol. Because of the absence of any easy ionizable moiety, these metabolites are poorly detectable using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI). In this study, the metabolism of methyltestosterone has been reinvestigated by the use of a precursor ion scan method in LC-ESI-MS/MS. Two metabolites have been detected using this method. Both compounds have been confirmed in postadministration urine samples of an urokinase plasminogen activator-severe combined immunodeficiency (uPA-SCID) mouse with humanized liver and were characterized by LC-MS/MS and GC-MS using both quadrupole and time of flight analyzers. From the detailed study of the fragmentation, these metabolites were proposed to be epimethyltestosterone and a dehydrogenated compound. Epimethyltestosterone has previously been described as a minor metabolite, whereas the occurrence of the oxidized metabolite has not been reported. Comparison with the synthesized reference revealed that the structure of the dehydrogenated metabolite is 6-ene-epimethyltestosterone. A selected reaction monitoring method including three transitions for each metabolite has been developed and applied to samples from an excretion study and to samples declared positive after GC-MS analysis. 6-Ene-epimethyltestosterone was found in all samples, showing its applicability in the detection of methyltestosterone misuse.Anabolic androgenic steroids are among the most frequently misused compounds by athletes (WADA Laboratory Statistics, 2009, http://www.wada-ama.org/en/dynamic.ch2?pageCategory.idϭ335). 17␣-Methyltestosterone (17␤-hydroxy-17␣-methylandrost-4-en-3-one) has been one of the most detected compounds in doping analysis during the past few years (WADA Laboratory Statistics, 2009, http:// www.wada-ama.org/en/dynamic.ch2?pageCategory.idϭ335). 17␣-Methyltestosterone is rapidly metabolized in humans, and therefore the monitoring of the misuse of this steroid is normally performed by the detection of its metabolites. Two main metabolites were identified in the metabolism of 17␣-methyltestosterone in human: 17␣-methyl-5␣-androstane-3␣,17␤-diol (A2) and 17␣-methyl-5␤-androstane-3␣,17␤-diol (A3) (Schänzer and Donike, 1993). Hydroxylated metabolites have been described in several animals including the horse (Dumasia, 2003;McKinney et al., 2007;Yamada et al., 2007) and the heifer (Blokland et al., 2005).In doping control analysis, the detection of steroid metabolites is normally performed by gas chromatography-mass spectrometry (GC-MS) after trimethylsilylation (Schänzer and Donike, 1993;Ayotte et al., 1996;Saugy et al., 2000), achieving the required sensitivity of 2 ng/ml (WADA Technical Document TD2004MRPL version 1.0, 2007, http://www.wada-ama.org/rtecontent/document...

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Section: Resultsmentioning

confidence: 70%

Detection and Characterization of a New Metabolite of 17α-Methyltestosterone

Pozo¹,

Eenoo²,

Deventer³

et al. 2009

Drug Metab Dispos

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“…This drug-testing paradigm was introduced in the 1960s (Table 1) and has since been remarkably successful in the detection of substances that are not naturally produced by the body, such as stimulants, narcotics, ␤2-agonists, and diuretics. This success is largely attributed to the use of chromatography coupled to mass spectrometry techniques that have revolutionized the detection of a large number of compounds (2 ).…”

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confidence: 99%

The Athlete Biological Passport

Sottas¹,

Robinson²,

et al. 2011

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BACKGROUND In elite sports, the growing availability of doping substances identical to those naturally produced by the human body seriously limits the ability of drug-testing regimes to ensure fairness and protection of health. CONTENT The Athlete Biological Passport (ABP), the new paradigm in testing based on the personalized monitoring of biomarkers of doping, offers the enormous advantage of being independent of this endless pharmaceutical race. Doping triggers physiological changes that provide physiological enhancements. In the same way that disease-related biomarkers are invaluable tools that assist physicians in the diagnosis of pathology, specifically selected biomarkers can be used to detect doping. SUMMARY The ABP is a new testing paradigm with immense potential value in the current climate of rapid advancement in biomarker discovery. In addition to its original aim of providing proof of a doping offense, the ABP can also serve as a platform for a Rule of Sport, with the presentation before competition of the ABP to objectively demonstrate that the athlete will participate in a healthy physiological condition that is unaltered by performance-enhancing drugs. Finally, the decision-support system used today for the biological monitoring of world top-level athletes can also be advantageously transferred to other areas of clinical practice to reach the goal of personalized medicine.

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“…The development of suitable analytical techniques for the characterization and analysis of steroids has been on-going for several decades. Mass spectrometry combined with chromatographic techniques has become very popular owing to its sensitivity and selectivity [9]. The analysis of steroids has been carried out by gas chromatography-mass spectrometry (GC-MS) [10][11][12][13][14][15][16], liquid chromatography-mass spectrometry (LC-MS) [17][18][19], electrospray mass spectrometry (ESI-MS) [20][21][22][23][24], atmospheric pressure chemical ionization mass spectrometry (APCI-MS) [25], matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) [26][27][28], and immunoassay [29].…”

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confidence: 99%

“…The analysis of steroids has been carried out by gas chromatography-mass spectrometry (GC-MS) [10][11][12][13][14][15][16], liquid chromatography-mass spectrometry (LC-MS) [17][18][19], electrospray mass spectrometry (ESI-MS) [20][21][22][23][24], atmospheric pressure chemical ionization mass spectrometry (APCI-MS) [25], matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) [26][27][28], and immunoassay [29]. Although GC-MS approaches are highly sensitive, they have some limitations due to the need for multistep derivatization procedures for these thermally-labile compounds, especially those that contain large numbers of hydroxyl groups [9,30,31]. In recent years, ESI-MS has been widely used for steroid analysis [32][33][34].…”

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confidence: 99%