IRMS of urinary norandrosterone in doping control analysis

More than 20 year ago IRMS has been established in routine doping control analysis to identify a potential exogenous origin of 19-norandrosterone (NorA) in urine samples. In the past the analysis of the carbon isotope ratio of urinary steroids offered the opportunity to distinguish between an endogenous or exogenous origin of the urinary steroids of interest with concentrations down to 2 ng/ml. Concerning NorA, urinary traces might not be only an indicator of an exogenous application, but may also originate from endogenous origin or from the consumption of wild boar offal and meat. Additionally, in some cases NorA can be formed in urine by in-situ microbial degradation of androsterone.

Since 2003 the Cologne laboratory analyzed approximately 300 doping control samples with NorA concentrations below 15 ng/ml by IRMS. Negative samples show similar δ¹³C values for NorA and the corresponding endogenous reference compounds, whereas NorA originating from pharmaceutical preparations usually showed ¹³C depleted values. However, within the last years the identification of an exogenous origin of urinary NorA became more and more challenging, as pharmaceutical preparations of NorA precursors exhibited more and more enriched δ¹³C values. Thus, an identification of such ‘pseudo-endogenous’ carbon isotope signatures by comparison with δ¹³C values of endogenous reference compounds is impeded. Due to this additional testing and follow-up investigation strategies had to be developed and implemented in doping control.