WADA Prohibited List: Peptides in Sports

# Introduction The World Anti-Doping Agency (WADA) regularly updates its list of prohibited substances, including peptides, to ensure fair play in sports [2][3][4][5][6]. These peptides, which are chains of amino acids linked by peptide bonds, have potential performance-enhancing effects, making them a target for anti-doping measures [9]. This review will discuss peptides that are currently on the WADA Prohibited List and the analytical approaches utilized in detecting these substances in human sports drug testing. # Preclinical Research Peptides, due to their potential performance-enhancing effects, have been the subject of extensive preclinical scrutiny [2][3][4][5][6]. However, the precise nature of these effects is not fully understood due to limited direct evidence from the provided citations. ## Desmopressin Desmopressin, a synthetic peptide, has been studied for its potential misuse in sports [1]. It is usually used medically to treat conditions such as diabetes insipidus and hemophilia A. However, its ability to increase the concentration of factor VIII and von Willebrand factor in plasma might be exploited for performance enhancement [1]. The molecules' detection was achieved using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) following urine delipidation [1]. ## Carbamylated Erythropoietin Carbamylated erythropoietin, a modified form of the hormone erythropoietin, has also been studied for its potential use in doping [7]. Erythropoietin stimulates the production of red blood cells, which can enhance endurance by increasing the oxygen-carrying capacity of the blood. Although carbamylated erythropoietin is not naturally occurring in humans, it can be synthesized and misused for doping purposes [7]. # Clinical Evidence While preclinical research provides important data on the potential misuse of peptides in sports, it's the clinical evidence that confirms their presence and misuse in actual sports scenarios [2][3][4][5][6]. ## Analytical Approaches To detect the misuse of peptides in sports, several analytical approaches have been developed. One of the most common methods is liquid chromatography coupled with high-resolution/high-accuracy mass spectrometry (LC-HRMS/MS) [4][5][6][8][10]. This method allows for the detection of a wide range of substances, including various classes of doping agents, in urine samples [10]. ## Detection of Specific Peptides The detection of specific peptides, such as inhibitors of the activin receptor signaling pathways (IASPs), has been achieved by means of LC-HRMS/MS [8]. IASPs have the potential to be misused in sports due to their ability to enhance muscle strength and mass, making their detection crucial for anti-doping efforts [8]. # Safety and Limitations While the detection methods for peptides have improved over the years, there are still challenges and limitations [9]. One of the biggest challenges is the detection of peptide hormones, which are typically present in very low concentrations in urine and can be rapidly metabolized [9]. Additionally, the wide variety of peptide substances and their potential modifications make it difficult to develop a single, comprehensive detection method [9]. Despite these challenges, the safety and fairness of sports rely heavily on the continued development and refinement of detection methods for prohibited substances. The current methods, while not perfect, provide a robust framework for the detection and deterrence of peptide misuse in sports. # Key Takeaways Peptides, due to their potential performance-enhancing effects, are included in the WADA Prohibited List. Several peptides, such as desmopressin and carbamylated erythropoietin, have been identified as potential doping agents. Analytical approaches, including LC-ESI-MS/MS and LC-HRMS/MS, have been developed to detect these substances in urine samples. Despite the challenges in detecting peptides, these methods play a crucial role in ensuring the integrity of sports.