The 2024 Summer Olympic Games: Mass Spectrometry's New Role in Sports and Understanding the Athlete's Exposome

2024 Olympic Games in Paris © Iliya Mitskavets - stock.adobe.com

As the 2024 Olympic Summer Games in Paris approach, the importance of stringent and effective athletic doping controls has never been more clear. These games represent not only the pinnacle of athletic achievement but also a global stage for demonstrating fair play and integrity in sports. With advancements in performance-enhancing substances and sophisticated methods of avoiding detection, it is imperative that anti-doping agencies employ cutting-edge analytical techniques and comprehensive testing protocols to ensure a level playing field. This commitment to clean competition not only safeguards the health and well-being of athletes but also upholds the Olympic spirit, fostering trust and admiration among spectators worldwide.

The field of sports drug testing has seen significant advancements, primarily driven by the need to stay ahead of the use of performance-enhancing drugs (PEDs). A recent paper by Mario Thevis, Christian Görgens, Sven Guddat, Andreas Thomas, and Hans Geyer from the Center for Preventive Doping Research at the German Sport University Cologne, published in the Scandinavian Journal of Medicine & Science in Sports, delves into the role of mass spectrometry in this ongoing battle. This study explores how modern analytical methods can better differentiate between intentional doping and inadvertent exposure to prohibited substances, a critical distinction for athletes facing rigorous anti-doping regulations (1).

Read More: Detection of Doping in Athletic Performance

Analytical Approaches in Anti-Doping

Since the 1960s, anti-doping efforts have advanced to incorporate the latest in mass spectrometry technology. Modern mass spectrometric methods undergo continuous optimization to improve comprehensiveness, sensitivity, and cost-effectiveness. The primary challenge is to ensure that these methods not only detect deliberate doping but also account for inadvertent exposure to environmental chemicals and drugs. The study emphasizes that distinguishing between doping and accidental contamination has become a central focus in anti-doping research (1).

The Athlete's Exposome

The exposome of any human encompasses the totality of environmental exposures an individual encounters throughout their lifetime, including chemicals, drugs, diet, and lifestyle factors. It provides a comprehensive framework for understanding how these exposures impact overall health, athletic performance, and onset of disease, integrating an understanding of external and internal factors.

Athletes are regularly subjected to doping controls, involving blood and urine tests that screen for a wide range of substances and metabolites. The presence of any prohibited substance can lead to severe consequences for an athlete’s career, raising questions about whether positive test results are due to intentional chemical use or accidental exposure (1). Other research has introduced the concept of the athlete's exposome—the totality of environmental exposures that athletes encounter—which can influence test outcomes. Understanding this exposome is essential for fair and accurate doping control (2).

Retrospective Analysis and Sensitivity

The study underscores the importance of improved analytical sensitivity, which allows for the detection of trace amounts of banned substances over extended periods. However, this heightened sensitivity also increases the likelihood of detecting substances from inadvertent exposure, such as contaminated food or environmental contact. The researchers highlight that distinguishing between these scenarios requires detailed knowledge of drug metabolism and elimination patterns, which can vary depending on the route of exposure (1).

Case Studies and Controlled Studies

Other research provides examples of how controlled studies can mimic inadvertent exposure scenarios to better understand drug and metabolite elimination profiles. One such example involves LGD-4033, a selective androgen receptor modulator. By examining the time-dependent conversion of LGD-4033 to its isomer, researchers can estimate the time of drug intake, aiding in differentiating between deliberate use and accidental contamination (3).

Another example involves clomiphene, where distinct metabolite patterns were observed in individuals who consumed clomiphene-contaminated eggs versus those who took the drug directly. These findings help establish protocols to differentiate between exposure and intentional use (4).

Complementary Strategies

To further enhance anti-doping efforts, research suggest more frequent sample collections and the use of minimally invasive techniques such as dried blood spots (DBS). These methods can create a "biobank" of samples for future analysis, supporting decision-making in cases of adverse analytical findings. Additionally, hair analysis has been shown to provide valuable information for case management, particularly in scenarios involving potential contamination from environmental sources (1).

Conclusion

The ever-advancing field of exposomics, combined with advancements in mass spectrometry, offers promising new approaches for anti-doping research. Thevis and his colleagues advocate for continued research to develop markers indicating the time and route of drug exposure, enhancing the ability to protect clean athletes while maintaining rigorous doping control standards. This study represents a significant step forward in ensuring fair play in sports through scientific innovation and detailed understanding of the athlete's environmental exposures (1).

References

(1) Thevis, M.; Görgens, C.; Guddat, S.; Thomas, A.; Geyer, H. Mass spectrometry in sports drug testing—analytical approaches and the athletes' exposome. Scand J Med Sci Sports. 2024, 34 (1), e14228. DOI: 10.1111/sms.14228

(2) Thevis, M.; Kuuranne, T.; Fedoruk, M.; Geyer, H. Sports drug testing and the athletes' exposome. Drug Test. Anal. 2021, 13 (11-12), 1814–1821. DOI: 10.1002/dta.3187

(3) Cox, H. D.; Eichner, D. Detection of LGD‐4033 and its metabolites in athlete urine samples. Drug Test. Anal. 2017, 9 (1), 127–134. DOI: 10.1002/dta.1986

(4) Euler, L.; Gillard, N.; Delahaut, P.; Pierret, G.; Mürdter, T.; Schwab, M.; Döhmen, G.; Thomas, A.; Thevis, M. Assessing human urinary clomiphene metabolites after consumption of eggs from clomiphene-treated laying hens using chromatographic-mass spectrometric approaches. Anal. Chim. Acta 2022, 1202, 339661. DOI: 10.1016/j.aca.2022.339661