Analytical approaches for the detection of emerging therapeutics and non-approved drugs in human doping controls.
This review summarizes five years of published literature on the analytical detection of emerging and non-approved performance-enhancing substances in the context of sports anti-doping controls. The authors examine a broad range of compounds classified as doping agents by the World Anti-Doping Agency (WADA), spanning both peptidic substances—such as modified insulin-like growth factor-1 (IGF-1), TB-500 (thymosin beta-4 fragment), peginesatide/hematide, growth hormone releasing peptides, and AOD-9604—and non-peptidic substances, including selective androgen receptor modulators (SARMs), hypoxia-inducible factor (HIF) stabilizers, siRNA, S-107, and aladorian (ARM036). Inorganic substances such as cobalt are also discussed. The review focuses specifically on the analytical challenges posed by these compounds, including their physicochemical properties, low concentrations in biological matrices (blood and urine), metabolic transformation, and suitability for chromatographic–mass spectrometric or alternative detection methods. The study does not present original experimental data or human clinical outcomes, but rather synthesizes existing literature to guide development of detection strategies. A key limitation is that, as a review, it does not independently validate any analytical method and reflects the state of the field only up to its publication date.
Why this grade: This is a narrative review synthesizing analytical detection literature; it generates no original human or animal experimental data and therefore does not provide direct evidence of efficacy or safety for any compound.
The number and diversity of potentially performance-enhancing substances is continuously growing, fueled by new pharmaceutical developments but also by the inventiveness and, at the same time, unscrupulousness of black-market (designer) drug producers and providers. In terms of sports drug testing, this situation necessitates reactive as well as proactive research and expansion of the analytical armamentarium to ensure timely, adequate, and comprehensive doping controls. This review summarizes literature published over the past 5 years on new drug entities, discontinued therapeutics, and 'tailored' compounds classified as doping agents according to the regulations of the World Anti-Doping Agency, with particular attention to analytical strategies enabling their detection in human blood or urine. Among these compounds, low- and high-molecular mass substances of peptidic (e.g. modified insulin-like growth factor-1, TB-500, hematide/peginesatide, growth hormone releasing peptides, AOD-9604, etc.) and non-peptidic (selective androgen receptor modulators, hypoxia-inducible factor stabilizers, siRNA, S-107 and ARM036/aladorian, etc.) as well as inorganic (cobalt) nature are considered and discussed in terms of specific requirements originating from physicochemical properties, concentration levels, metabolism, and their amenability for chromatographic-mass spectrometric or alternative detection methods.
Educational summary of published research — not medical advice. Full text is shown only where licensing permits.