Analytical challenges in sports drug testing

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.

[1]  M. Thevis,et al.  lmplementation of the prolyl hydroxylase inhibitor Roxadustat (FG-4592) and its main metabolites into routine doping controls. , 2017, Drug testing and analysis.

[2]  M. Thevis,et al.  Sports drug testing: Analytical aspects of selected cases of suspected, purported, and proven urine manipulation. , 2012, Journal of pharmaceutical and biomedical analysis.

[3]  M. Thevis,et al.  Detection of SARMs in doping control analysis , 2017, Molecular and Cellular Endocrinology.

[4]  J. Dvořák,et al.  Adverse analytical findings with clenbuterol among U-17 soccer players attributed to food contamination issues. , 2013, Drug testing and analysis.

[5]  M. Parr,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 , 2017, Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment.

[6]  C. Buisson,et al.  Detection by LC-MS/MS of HIF stabilizer FG-4592 used as a new doping agent: Investigation on a positive case. , 2016, Journal of pharmaceutical and biomedical analysis.

[7]  Yu-Chen Chang,et al.  Tetrahydrogestrinone: discovery, synthesis, and detection in urine. , 2004, Rapid communications in mass spectrometry : RCM.

[8]  M. Thevis,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. , 2016, Forensic Science International.

[9]  A. Billin PPAR-beta/delta agonists for Type 2 diabetes and dyslipidemia: an adopted orphan still looking for a home. , 2008, Expert opinion on investigational drugs.

[10]  M. Thevis,et al.  Characterization of two major urinary metabolites of the PPARδ-agonist GW1516 and implementation of the drug in routine doping controls , 2010, Analytical and bioanalytical chemistry.

[11]  W. Jelkmann,et al.  Investigational therapies for renal disease-induced anemia , 2016, Expert opinion on investigational drugs.

[12]  J. Dvořák,et al.  Statistical significance of hair analysis of clenbuterol to discriminate therapeutic use from contamination. , 2014, Drug testing and analysis.

[13]  M. Thevis,et al.  Antibody-based strategies for the detection of Luspatercept (ACE-536) in human serum. , 2017, Drug testing and analysis.

[14]  L. Henke,et al.  Detection of manipulation in doping control urine sample collection: a multidisciplinary approach to determine identical urine samples , 2007, Analytical and bioanalytical chemistry.

[15]  N. Baume,et al.  SARM-S4 and metabolites detection in sports drug testing: a case report. , 2011, Forensic science international.

[16]  D. Eichner,et al.  Detection of LGD-4033 and its metabolites in athlete urine samples. , 2017, Drug testing and analysis.

[17]  J. Dalton,et al.  Selective androgen receptor modulators for the prevention and treatment of muscle wasting associated with cancer , 2013, Current opinion in supportive and palliative care.

[18]  M. Thevis,et al.  Formation of the diuretic chlorazanil from the antimalarial drug proguanil--implications for sports drug testing. , 2015, Journal of pharmaceutical and biomedical analysis.

[19]  M. Thevis,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. , 2017, Drug testing and analysis.

[20]  Maria M. Mihaylova,et al.  AMPK and PPARδ Agonists Are Exercise Mimetics , 2008, Cell.

[21]  M. Thevis,et al.  Testing for the erythropoiesis-stimulating agent Sotatercept/ACE-011 (ActRIIA-Fc) in serum by means of Western blotting and LC-HRMS. , 2016, Drug testing and analysis.

[22]  D. Volmer,et al.  Mass spectrometric studies on selective androgen receptor modulators (SARMs) using electron ionization and electrospray ionization/collision-induced dissociation , 2018, European journal of mass spectrometry.