Independent Observer Report : Tour de France 2010 / Independent Observer Team. - Montreal : World Anti-Doping Agency (WADA), 2010

Independent Observer Report : Tour de France 2003 / Independent Observer Team. - Montreal : World Anti-Doping Agency (WADA), 2003

Report of the Independent Observers : the 8th World Games, Kaohsiung, July 2009 / Independent Observer Team. - Montreal : World Anti-Doping Agency (WADA), 2009

WADA Independent Observer Report African Games, 2019, Rabat, Morocco / Independent Observer Team. - Montreal : World Anti-Doping Agency (WADA), 2019

Phytosterols and anabolic agents versus designer drugs / H.F. De Brabander, K. Verheyden, V. Mortier, B. Le Bizec, W. Verbeke, D. Courtheyn, H. Noppe. - (Analytica Chimica Acta 586 (2007) 1-2 (14 March); p. 49-56)

• PMID: 17386696
• DOI: 10.1016/j.aca.2006.07.031

Abstract

Cholesterol is a well-known component in fats of animal origin and it also is the precursor of natural hormones. Phytosterols appear in plants and only differ slightly in structure from cholesterol. An important difference however is the low absorption in the gut of phytosterols and their saturated derivatives, the phytostanols. As a result, there is time for all kind of reactions in faecal material inside and outside of the gut. Determination of the abuse of natural hormones may be based on gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Abuse of natural hormones changes the 13C/12C ratio of some metabolites during a relatively long time. The formation of (natural) hormones in the gut may interfere with this method. Designer drugs are mainly known from sports doping. In animal fattening, designer drugs may be used as well. Small changes in the structure of (natural) hormones may lead to a new group of substances asking for new strategies for their detection and the constatation of their abuse.

Phytosterol consumption and the anabolic steroid boldenone in humans: a hypothesis piloted / M.M. Ros, S.S. Sterk, H. Verhagen, A.F.H. Stalenhoef, N. de Jong. - (Food Additives & Contaminants 24 (2007) 7 (July); p. 679-684)

• PMID: 17613052
• DOI: 10.1080/02652030701216727

Abstract

The presence of the anabolic steroid boldenone in animals has become a research topic as its occurrence is proposed to be a marker for illegal hormone administration. However, boldenone can also be formed from beta-sitosterol, a phytosterol present in animal feed, as well as from endogenous sources. The observations in animals together with the increased consumption of phytosterol-enriched foods in the Western population led the authors to the hypothesis that consumption of phytosterol-enriched foods might possibly lead to increased boldenone levels in humans. The authors performed a pilot study among female volunteers (n = 10) to investigate whether boldenone concentrations in urine were detectable after consumption of 25 g day(-1) of phytosterol-enriched margarines for 1 week. Urine samples were collected at days 0, 3 or 4, and 7. Urine of a sitosterolemia (a rare autosomal recessively inherited lipid metabolic disorder) patient was collected as a positive control case. No traces of boldenone were detected in either the volunteers or in the patient. In conclusion, there is no evidence of formation of boldenone in women after consumption of the recommended amount of phytosterol-enriched margarines.

Schemes of metabolic patterns of anabolic androgenic steroids for the estimation of metabolites of designer steroids in human urine / A.G. Fragkaki, Y.S Angelis, A. Tsantili-Kakoulidou, M. Koupparis, C. Georgakopoulos. - (The Journal of Steroid Biochemistry and Molecular Biology 115 (2009) 1-2 (May); p. 44-61)

• PMID: 19429460
• DOI: 10.1016/j.jsbmb.2009.02.016

Abstract

Unified metabolism schemes of anabolic androgenic steroids (AAS) in human urine based on structure classification of parent molecules are presented in this paper. Principal components analysis (PCA) was applied to AAS molecules referred in the World Anti-Doping Agency (WADA) list of prohibited substances, resulting to their classification into six distinct groups related to structure features where metabolic alterations usually occur. The metabolites of the steroids participating to these six groups were treated using the Excel(c) classification filters showing that common metabolism routes are derived for each of the above PCA classes, leading to the proposed metabolism schemes of the present study. This rule-based approach is proposed for the prediction of the metabolism of unknown, chemically modified steroids, otherwise named as designer steroids. The metabolites of three known, in the literature, AAS are estimated using the proposed metabolism schemes, confirming that their use could be a useful tool for the prediction of metabolic pathways of unknown AAS.

Structure characterisation of urinary metabolites of the cannabimimetic JWH-018 using chemically synthesised reference material for the support of LC-MS/MS-based drug testing / Simon Beuck, Ines Möller, Andreas Thomas, Annika Klose, Nils Schlörer, Wilhelm Schänzer, Mario Thevis. - (Analytical and Bioanalytical Chemistry 401 (2011) 2 (August); p. 493-505)

• PMID: 21455647
• DOI: 10.1007/s00216-011-4931-5

Abstract

As recently reported, the synthetic cannabinoid JWH-018 is the subject of extensive phase I and II metabolic reactions in vivo. Since these studies were based on LC-MS/MS and/or GC-MS identification and characterisation of analytes, the explicit structural assignment of the metabolites was only of preliminary nature, if possible at all. Here, we report the chemical synthesis of five potential in vivo metabolites of JWH-018 derivatives featuring an alkylcarboxy (M1), a terminal alkylhydroxy (M2), a 5-indolehydroxy (M3), an N-dealkylated 5-indolehydroxy (M4) and a 2'-naphthylhydroxy (5) analogue, respectively, and their characterisation by nuclear magnetic resonance spectroscopy. The collision-induced dissociation (CID) patterns of the protonated compounds were studied by high-resolution/high-accuracy tandem mass spectrometry (MS( n )) applying an LTQ Orbitrap with direct infusion and electrospray ionisation of target analytes. An unusual dissociation behaviour including a reversible ion-molecule reaction between a naphthalene cation (m/z 127) and water in the gas phase of the MS was shown to be responsible for nominal neutral losses of 10 u in the course of the CID pathway. LC-MS/MS-supported comparison of synthesised reference standards with an authentic urine sample using an API 4000 QTrap mass spectrometer identified the synthetic JWH-018 analogues M1-M4 as true in vivo metabolites, presuming a chromatographic separation of potentially present regioisomeric analogues. Existing doping control methods were expanded and validated according to international guidelines in order to allow for the detection of the carboxy and the alkylhydroxy metabolites, respectively, as urinary markers for the illegal intake of the synthetic cannabinoid JWH-018. Both metabolites were quantified in authentic doping control urine samples that had been suspicious of JWH-018 abuse after routine screening procedures, and a stable isotope-labelled (13)C(8)-(15)N-carboxy metabolite was synthesised for future analytical applications.

Metabolism of anabolic androgenic steroids / W. Schänzer. - (Clinical Chemistry 42 (1996) 7 (July); p. 1001-1020)

• PMID: 8674183
• DOI: 10.1093/clinchem/42.7.1001

Abstract

Anabolic androgenic steroids (AAS) are misused to a high extent in sports by athletes to improve their physical performance. Sports federations consider the use of these drugs in sports as doping. The misuse of AAS is controlled by detection of the parent AAS (when excreted into urine) and (or) their metabolites in urine of athletes. I present a review of the metabolism of AAS. Testosterone is the principal androgenic steroid and its metabolism is compared with that of AAS. The review is divided into two parts: the general metabolism of AAS, which is separated into phase I and phase II metabolism and includes a systematic discussion of metabolic changes in the steroid molecule according to the regions (A-D rings), and the specific metabolism of AAS, which presents the metabolism of 26 AAS in humans.

Screening for 2-quinolinone-derived selective androgen receptor agonists in doping control analysis / Mario Thevis, Maxie Kohler, Joachim Maurer, Nils Schlörer, Matthias Kamber, Wilhelm Schänzer. - (Rapid Communicaton in Mass Spectrometry 21 (2007) 21 (15 November); p. 3477-3486)

• PMID: 17985352
• DOI: 10.1002/rcm.3247

Abstract

Selective androgen receptor modulators (SARMs) represent a class of emerging drugs with high potential for misuse in sports, and therefore members of this group are banned as anabolic agents by the World Anti-Doping Agency. Preventive approaches to restrict their use include early implementation of target analytes into doping control screening assays and evaluation of the mass spectrometric behavior of these drugs to allow their unequivocal identification as well as the characterization of structurally related compounds and metabolic products. Four model SARMs with the 6-alkylamino-2-quinolinone structure, including the advanced drug candidate LGD-2226, were synthesized. Fragmentation pathways after positive electrospray ionization and collision-induced dissociation were studied using an LTQ Orbitrap mass analyzer, and diagnostic product ions and common dissociation pathways were employed to establish a screening procedure targeting intact quinolinone-based SARMs as well as putative metabolic products such as dealkylated analogues. Therefore, features of a triple quadrupole mass analyzer such as multiple reaction monitoring and precursor ion scanning were utilized. Sample preparation based on commonly employed liquid-liquid extraction and subsequent liquid chromatographic/tandem mass spectrometric measurement allowed for detection limits of 0.01-0.2 ng/mL, and intra- and interday precisions between 3.2 and 8.5% and between 6.3 and 16.6%, respectively. Recoveries varied from 81 to 98%, and tests for ion suppression or enhancement effects were negative for all analytes.