Synthetic applications in analytical chemistry

Identifying and analyzing drug candidates with potential performance-enhancing properties is a key aspect of our profession. To establish a proactive doping control system, such substances must be investigated as early as possible to allow for their detection and, thereby, deterrence of misuse as doping agents. However, such substances and associated internal standards are rarely available. In these cases, chemical synthesis might be the only option to address this issue. Through in-house synthesis, new and potentially doping-relevant substances can be synthesized and analyzed on-site. Further analysis of their analytical characteristics and their metabolic behavior is then enabled, supporting the development of suitable methods for detecting these compounds and their associated metabolites in doping controls. Therefore, in vitro incubation and/or synthesis of potential metabolites are crucial for a comprehensive anti-doping system. This work aims to illustrate the use of organic synthesis for doping control analysis, with an emphasis on its application and practicality in daily lab work. The substances investigated in this study range from selective androgen receptor modulators (SARMs) to ryanodine channel complex stabilizers (Rycals) and estrogen-related receptor agonists (pan ERR agonists). Additionally, SARM 2f, as well as the Rycal compounds S107, JTV 519, ARM036, and ARM210 were metabolized in vitro to identify potential metabolites. Selected metabolites of SARM 2f and the various Rycal compounds were synthesized to confirm their structure and provide reference materials for anti-doping control purposes. Through this presentation, we hope to encourage others to synthesize reference standards and demonstrate that these synthetic methods can be applied in any lab. The results of this study contribute to expanding our knowledge of new substances and their metabolic properties, and the compounds synthesized here can serve as reference materials in routine anti-doping controls.