Confirmation of endogenous substance abuse in doping control by isotope ratio mass spectrometry

All doping control laboratories accredited by the World Anti-Doping Agency have been confronted with the task to develop analytical methods and establish criteria that allow endogenous substances to be distinguished from their synthetic copies. It has been known for some time that isotope ratio mass spectrometry (IRMS) is capable of meeting this challenge because endogenous and exogenous substances exhibit different isotope ratios. At this stage, the technique is primarily used for the differentiation between endogenous and exogenous steroids by comparison of the 13C/12C ratios. Endogenous reference compounds (ERC’s) are compounds of which the isotope ratio does not change after synthetic steroid administration. By comparison of the 13C/12C ratios of ERC’s with that of target compounds like testosterone and its metabolites, it is possible to differentiate between an exogenous or endogenous origin. Obviously, IRMS is not limited to steroids and 13C/12C measurements. The Technique can also be used for other endogenous substances that are known to be misused as doping, such as for example AICAR and adrenaline. Both compounds contain nitrogen, making 15N/14N ratio analysis a valuable option. Results of several new methods developed on IRMS will be discussed