Analysis of New Chemical Entities in a Sport Context

Abstract

The Prohibited List of the World Anti-Doping Agency (WADA) defines the analytical framework for the anti-doping laboratories by introducing the substances and methods banned in sport context and which shall be incorporated into the analytical test menus in order to comply with the accreditation requirements and to ensure globally harmonized performance. The process of extending the list with new compounds may be initiated by the annual list review process by the experts, who evaluate, e.g., the recent scientific updates on the performance-enhancing substances originating from pharmaceutical drug development or illicit sources, as a result from the information gathered within monitoring programmes, or via other investigational information from anti-doping organizations or various authorities. Whichever is the source of a new chemical entity with doping potential, efficient analysis of anti-doping samples requires information on the pharmacokinetic and metabolic properties of the substance in order to set the routine analytical test to monitor representative target compounds in an appropriate biological matrix, at fit-for-purpose sensitivity, at reasonable workload and at optimal costs. For identification purposes, characterized reference material is needed, and especially for the metabolites of illicit drugs, the production process can be hindered by the lack of proper information for chemical synthesis, unavailability of starting material for in vitro assays and ethical issues for human administration. As part of the method validation, the anti-doping laboratory shall assess the selectivity of the method and take all the precautions to exclude any non-prohibited source as origin of the analytical finding prior to reporting. In addition to high reactivity of routine screening, also retrospective analysis of digitally archived data and long-term sample storage combined with well-planned and timed further analysis programmes may deter athletes from doping but also provide the opportunity to study the emergence of new chemical entities.