Winning the Sports Drug Arms Race

Recent confessions by convicted athletes have exposed the impact of drugs on sport. They have also demonstrated the influence that sport drug testing analytical strategies have on doping behavior. Although there is no guarantee that the confessions are comprehensive and exhaustive, the trend is clear: Whenever a doping method/drug becomes detectable, ways to undermine the improved control system are sought. It’s doping’s own form of an arms race.

Doping control analysis is a constant challenge. An important and integral part of international anti-doping efforts, the analyses must cover an ever-increasing collection of opportunities, both theoretical and practical, that are open to cheating athletes. These include the misuse of approved drugs, such as anabolic agents and erythropoiesis-stimulating substances; the administration of emerging drugs – with and without clinical approval; designer substances; and methods of doping such as blood transfusion and gene doping. Tests are required that, for example, unequivocally identify long-term metabolites of xenobiotics; that distinguish minute differences between naturally (and endogenously) occurring compounds such as testosterone, growth hormone, or erythropoietin, and their synthetic analogs; and that discriminate trace amounts of drug-derived banned substances from the naturally produced counterpart from urine or blood. All this is required on a routine basis - a demanding, while at the same time logical and indispensable, task.

How has the arms race developed? When testing was first introduced, out-of-competition controls were rare. So, doping athletes simply allowed sufficient time for prohibited substances to be eliminated from their bodies to ensure negative tests during and post-competition. With the introduction of unannounced out-of-competition controls, new/alternative drugs that were not detectable became favored. A prominent example is erythropoietin (EPO), which was not distinguishable from the natural hormone for almost a decade after the therapeutic agent was launched. Many athletes (they now admit) abused the drug to a considerable extent, illicitly increasing their endurance performance without risk of being discovered in doping control tests. 

When analytical methods became available to identify recombinant EPO in human urine and blood, homologous blood transfusion (HBT) became a method of choice, followed by autologous blood transfusions (ABT) when HBT could be successfully tested for. Now, the implementation of the Athlete Biological Passport (1), which detects non-natural alterations of an individual’s blood parameter profile, severely limits the options on blood doping. 

There have been comparable developments with anabolic-androgenic steroids. Analysis of xenobiotic steroidal substances has been significantly improved, with the development of new instruments and identification of long-term metabolites. This has led to increased misuse of testosterone and, arguably, of unknown (and hence undetectable) ‘tailor-made’ steroids. Fortunately, steroid profiling and isotope-ratio mass spectrometry have now been established as a reliable means to reveal these doping practices.

Despite these substantial improvements to doping controls over the last decade, new loopholes are constantly being exploited by cheating athletes. One anti-doping tool of great utility, therefore, is long-term sample storage with the option of re-analysis. There are a number of examples of applying optimized test methods to long-term stored specimens to uncover doping. In combination with legislation on the consequences of adverse analytical findings, this strategy should effectively deter and discourage drug use, hopefully drawing the doping arms race to a successful conclusion.