Abstract
Analytical chemistry represents a central aspect of doping controls. Routine sports drug testing approaches are primarily designed to address the question whether a prohibited substance is present in a doping control sample and whether prohibited methods (for example, blood transfusion or sample manipulation) have been conducted by an athlete. As some athletes have availed themselves of the substantial breadth of research and development in the pharmaceutical arena, proactive and preventive measures are required such as the early implementation of new drug candidates and corresponding metabolites into routine doping control assays, even though these drug candidates are to date not approved for human use. Beyond this, analytical data are also cornerstones of investigations into atypical or adverse analytical findings, where the overall picture provides ample reason for follow-up studies. Such studies have been of most diverse nature, and tailored approaches have been required to probe hypotheses and scenarios reported by the involved parties concerning the plausibility and consistency of statements and (analytical) facts. In order to outline the variety of challenges that doping control laboratories are facing besides providing optimal detection capabilities and analytical comprehensiveness, selected case vignettes involving the follow-up of unconventional adverse analytical findings, urine sample manipulation, drug/food contamination issues, and unexpected biotransformation reactions are thematized.
Similar content being viewed by others
References
WADA. The 2018 Prohibited List. Montreal: Wolrd Anti-Doping Agency; 2017 [cited 26.10.2017]. Available from: https://www.wada-ama.org/sites/default/files/prohibited_list_2018_en.pdf.
Kidd B, Edelman R, Brownell S. Comparative analysis of doping scandals: Canada, Russia, and China. In: Wilson W, Derse E, editors. Doping in elite sport. Chamaign: Human Kinetics; 2001. p. 153–88.
Catlin DH, Sekera MH, Ahrens BD, Starcevic B, Chang Y-C, Hatton CK. Tetrahydrogestrinone: discovery, synthesis, and detection in urine. Rapid Commun Mass Spectrom. 2004;18(12):1245–9.
Dalton JT, Taylor RP, Mohler ML, Steiner MS. Selective androgen receptor modulators for the prevention and treatment of muscle wasting associated with cancer. Curr Opin Support Palliat Care. 2013;7(4):345–51.
Grata E, Perrenoud L, Saugy M, Baume N. SARM-S4 and metabolites detection in sports drug testing: a case report. Forensic Sci Int. 2011;213(1–3):104–8.
Thevis M, Volmer DA. Mass spectrometric studies on selective androgen receptor modulators (SARMs) using electron ionization and electrospray ionization/collision-induced dissociation. Eur J Mass Spectrom. 2017;23. https://doi.org/10.1177/1469066717731228.
Cox HD, Eichner D. Detection of LGD-4033 and its metabolites in athlete urine samples. Drug Test Anal. 2017;9(1):127–34.
McLaren R. The Independent Person 2nd Report: Richard McLaren; 2016 [cited 27.10.2017]. Available from: https://www.wada-ama.org/sites/default/files/resources/files/mclaren_report_part_ii_2.pdf.
Perrenoud L, Schweizer Grundisch C, Baume N, Saugy M, Nicoli R. Risk of false positive results to SARM S-4 in case of therapeutic use of antineoplastic/antiandrogen drug containing flutamide: a case study. Drug Test Anal. 2016;8(11–12):1109–13.
Thevis M, Schänzer W. Detection of SARMs in doping control analysis. Mol Cell Endocrinol. 2017;in press; https://doi.org/10.1016/j.mce.2017.01.040.
Narkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, et al. AMPK and PPARdelta agonists are exercise mimetics. Cell. 2008;134(3):405–15.
Billin AN. PPAR-beta/delta agonists for type 2 diabetes and dyslipidemia: an adopted orphan still looking for a home. Expert Opin Investig Drugs. 2008;17(10):1465–71.
Thevis M, Möller I, Thomas A, Beuck S, Rodchenkov G, Bornatsch W, et al. Characterization of two major urinary metabolites of the PPARdelta-agonist GW1516 and implementation of the drug in routine doping controls. Anal Bioanal Chem. 2010;396(7):2479–91.
Schmid H, Jelkmann W. Investigational therapies for renal disease-induced anemia. Expert Opin Investig Drugs. 2016;25(8):901–16.
Eichner D, Van Wagoner RM, Brenner M, Chou J, Leigh S, Wright LR, et al. Implementation of the prolyl hydroxylase inhibitor Roxadustat (FG-4592) and its main metabolites into routine doping controls. Drug Test Anal. 2017; https://doi.org/10.1002/dta.2202.
Dib J, Mongongu C, Buisson C, Molina A, Schänzer W, Thuss U, et al. Mass spectrometric characterization of the hypoxia-inducible factor (HIF) stabilizer drug candidate BAY 85-3934 (molidustat) and its glucuronidated metabolite BAY-348, and their implementation into routine doping controls. Drug Test Anal. 2017;9:61–7.
Buisson C, Marchand A, Bailloux I, Lahaussois A, Martin L, Molina A. Detection by LC-MS/MS of HIF stabilizer FG-4592 used as a new doping agent: investigation on a positive case. J Pharm Biomed Anal. 2016;121:181–7.
CyclingNews. Kvasina positive for EPO stimulator at Fleche du Sud: CyclingNews; 2017 [cited 05–07-2017]. Available from: http://www.cyclingnews.com/news/kvasina-positive-for-epo-stimulator-at-fleche-du-sud/.
Walpurgis K, Thomas A, Vogel M, Reichel C, Geyer H, Schänzer W, et al. Testing for the erythropoiesis-stimulating agent Sotatercept/ACE-011 (ActRIIA-Fc) in serum by means of western blotting and LC-HRMS. Drug Test Anal. 2016;8(11–12):1152–61.
Reichel C, Gmeiner G, Thevis M. Antibody-based strategies for the detection of luspatercept (ACE-536) in human serum. Drug Test Anal. 2017; https://doi.org/10.1002/dta.2302.
WADA. World Anti-Doping Code. Montreal: World Anti-Doping Agency; 2015 [cited 12–04-2016]. Available from: https://wada-main-prod.s3.amazonaws.com/resources/files/wada-2015-world-anti-doping-code.pdf.
Thevis M, Geyer L, Geyer H, Guddat S, Dvorak J, Butch A, et al. Adverse analytical findings with clenbuterol among U-17 soccer players attributed to food contamination issues. Drug Test Anal. 2013;5:372–6.
Krumbholz A, Anielski P, Gfrerer L, Graw M, Geyer H, Schanzer W, et al. Statistical significance of hair analysis of clenbuterol to discriminate therapeutic use from contamination. Drug Test Anal. 2014;6(11–12):1108–16.
Parr MK, Blokland MH, Liebetrau F, Schmidt AH, Meijer T, Stanic M, et al. Distinction of clenbuterol intake from drug or contaminated food of animal origin in a controlled administration trial—the potential of enantiomeric separation for doping control analysis. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2017;34(4):525–35.
Helmlin H-J, Mürner A, Steiner S, Kamber M, Weber C, Geyer H, et al. Detection of the diuretic hydrochlorothiazide in a doping control urine sample as the result of a non-steroidal anti-inflammatory drug (NSAID) tablet contamination. Forensic Sci Int. 2016;267:166–72.
USADA. U.S. Volleyball Athlete Alexandra Klineman Accepts Finding of No Fault for Anti-Doping Rule Violation Colorado Springs: U.S. Anti-Doping Agency; 2017 [cited 17–11-2017]. Available from: https://www.usada.org/alexandra-klineman-accepts-finding-no-fault/.
Thevis M, Geyer H, Thomas A, Tretzel L, Bailloux I, Buisson C, et al. Formation of the diuretic chlorazanil from the antimalarial drug proguanil—implications for sports drug testing. J Pharm Biomed Anal. 2015;115:208–13.
Thevis M, Geyer H, Sigmund G, Schänzer W. Sports drug testing: analytical aspects of selected cases of suspected, purported, and proven urine manipulation. J Pharm Biomed Anal. 2012;57:26–32.
Geyer H, Mareck U, Schänzer W, Donike M, editors. The cologne protocol to follow up high testosterone/epitestosterone ratios. Recent advances in doping analysis. Cologne: Sport und Buch Strauss; 1997.
Thevis M, Geyer H, Mareck U, Sigmund G, Henke J, Henke L, et al. Detection of manipulation in doping control urine sample collection: a multidisciplinary approach to determine identical urine samples. Anal Bioanal Chem. 2007;388:1539–43.
Acknowledgments
The authors thank the Manfred-Donike-Institute for Doping Analysis (Cologne, Germany) and the Federal Ministry of the Interior of the Federal Republic of Germany (Bonn, Germany) for the support.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Thevis, M., Krug, O., Geyer, H. et al. Analytical challenges in sports drug testing. Anal Bioanal Chem 410, 2275–2281 (2018). https://doi.org/10.1007/s00216-018-0934-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-018-0934-9