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A biomarker of doping indicates the biological response to the use of a prohibited substance or method. Uncovering novel biomarkers of doping is a key objective in order to improve antidoping outcomes such as the detection of doping and changing athlete behavior toward doping practices. While the antidoping field has been successful in validating novel metabolites of prohibited substances, there has been less success in developing new biomarkers of doping. Employing the most suitable study designs and analytical approaches is critical to successfully uncovering novel biomarkers of doping with a high potential for translation into routine analysis. Here we argue that the antidoping field is well positioned for biomarker discovery and outline considerations for the development of novel biomarkers of doping.

Meldonium is a metabolic drug whose inclusion in the 2016 List of Prohibited Substances and Methods followed the analysis of data collected under the 2015 World Anti-Doping Agency Monitoring Program. In the early months of 2016, anti-doping laboratories reported an unusually high number of cases in which urine samples contained high concentrations of meldonium. Consequently, the meldonium excretion period in healthy athletes and the substance's long-term urine and blood (plasma) pharmacokinetics became central questions for the anti-doping community to address, to ensure appropriate assessment of the scientific and medical situation, and also fair treatment of athletes from a result management and legal standpoint. At the present time, data on meldonium pharmacokinetics is limited to a few studies, with no known data available on long-term excretion of high oral doses. The primary objective of this open-label study was to determine long-term urine and plasma pharmacokinetic parameters of meldonium in healthy volunteers. Study design included single and repeated functional load testing and assessment of L-carnitine administration on meldonium excretion and pharmacokinetics. Thirty-two volunteers were equally divided into two groups receiving either 1.0 g or 2.0 g of oral meldonium daily for 3 weeks. The study found meldonium takes several days to attain a steady state in blood and displays an elimination period over several months after cessation of treatment. Moreover, findings demonstrate that the daily dose, periodicity and duration of treatment with meldonium are the most important factors to consider in calculating the substance's elimination and complete body clearance.

The worldwide network of World Anti-Doping Agency (WADA)-accredited anti-doping laboratories plays a fundamental role in supporting the global fight against doping in sport. This role is dependent on the ability to provide accurate, reliable and comparable data in identifying and measuring the presence of prohibited substances and methods. The accredited laboratories participate in WADA’s External Quality Assessment Scheme (EQAS) program, which provides the structure to continuously assess and improve laboratory performance in compliance to the requirements of the International Standard for Laboratories and related Technical Documents. The WADA EQAS is comprised of various programs, including a blind EQAS, a double-blind EQAS and an educational EQAS, each with specific goals with regard to monitoring and improving laboratory competence. In this article, the anti-doping rules and processes that govern granting and maintenance of WADA laboratory accreditation, aimed at ensuring a high-quality of laboratory operations within the framework of the global fight against doping in sport, are reviewed.

This article provides a review of the leading role of the World Anti-Doping Agency (WADA) in the context of the global fight against doping in sport and the harmonization of anti-doping rules worldwide through the implementation of the World Anti-Doping Program. Particular emphasis is given to the WADA-laboratory accreditation program, which is coordinated by the Science Department of WADA in conjunction with the Laboratory Expert Group, and the cooperation with the international accreditation community through International Laboratory Accreditation Cooperation and other organizations, all of which contribute to constant improvement of laboratory performance in the global fight against doping in sport. A perspective is provided of the means to refine the existing anti-doping rules and programs to ensure continuous improvement in order to face growing sophisticated challenges. A viewpoint on WADA’s desire to embrace cooperation with other international organizations whose knowledge can contribute to the fight against doping in sport is acknowledged.

The List of Prohibited Substances and Methods (the List) is the International Standard that determines what is prohibited in sport in- and out-of-competition. The official text of the List is produced by the World Anti-Doping Agency (WADA), the international independent organization responsible for promoting, coordinating and monitoring the fight against doping in sport. The drafting of the annual List is a highly interactive and consultative process involving scientific and medical experts in anti-doping, sport federations and governments. In this article, the elements that compose the List as well as the process behind its annual revision and update are presented.

Due to its considered performance enhancing effects, human growth hormone (hGH) is abused as a doping agent in sport. Its misuse also carries potentially serious side effects to a person's health. Consequently, hGH and its releasing factors are prohibited in sport, as established in the Prohibited List which is updated and published yearly by the World Anti-Doping Agency (WADA). In order to fight the menace that hGH doping poses to the spirit of sport and to the health of athletes, the sport movement and the anti-doping authorities, initially led by the International Olympic Committee (IOC) and later by WADA, have put substantial efforts into developing tests for its detection. Currently, a primary analytical approach, the isoform differential immunoassay, has been implemented in WADA-accredited laboratories. In parallel, a second, indirect approach for the detection of hGH abuse, based on the quantification of hGH-associated biological markers, has been developed. The final aim is to combine both methodologies to improve the sensitivity and expand the time window to detect doping with hGH. In addition, novel analytical procedures, based on proteomic and genomic technologies as well as the use of mass spectrometry-based methods of detection, are being investigated for future application in hGH anti-doping tests.

The effects of anoxia and reoxygenation on major antioxidant enzyme activities were investigated in vitro in immortalized rat brain endothelial cells (RBE4 cells). A sublethal anoxic period of 12 h was assessed for RBE4 cells using the neutral red uptake test. Anoxia markedly influenced the specific activity of catalase and superoxide dismutase, with no major effect on glutathione peroxidase or glutathione reductase. After 24 h postanoxia, the superoxide dismutase activity modulated by the presence or absence of oxygen returned to control value. Damage and recovery of RBE4 immortalized rat brain endothelial cells in culture after exposure to free radicals and other oxygen-derived species provides a useful in vitro model to study anoxia-reoxygenation trauma at the cellular level.

Most substances used for doping in sport are legitimate pharmaceutical products deviated from their intended therapeutic applications. One of the major challenges for anti-doping authorities, in anticipation of future doping trends, is to assess the doping potential of drugs in development by the health industry and to timely develop anti-doping analytical methods to detect their abuse before such drugs become available to athletes intending to use them as doping agents. In this regard, the World Anti-Doping Agency (WADA) has recently consolidated several agreements with representatives from the pharmaceutical sector in order to establish a framework of collaboration and to facilitate the identification and transfer of information on drugs in development. The context of the collaborative effort between WADA and the pharmaceutical and biotechnology industries, as well as the role of drug regulatory agencies in an integrated process in support of the fight against doping in sport are described in this article.

We humans have long sought to enhance ourselves beyond normal through cosmetic surgery and drugs. Science is increasingly becoming humanity's partner and handmaiden in those efforts ( 1 ) and has added genetic manipulation to our enhancement tool kit. Many forms of human enhancement are becoming more feasible, sought-after, and even justifiable in the quest for healthier, happier, and longer lives.