LC-IRMS in antidoping analysis: confirming the exogenous administration of AICAR, endogenous bioamines, and IGF-1

Code: 22A08XT

For substances produced endogenously and included in the WADA Prohibited List, its abuse is based on: 10 identification of the best biomarker of abuse to be applied at the ITP level and 2) confirmation by a procedure able to demonstrate the application of the drug or its origin. Usually, this is performed by establishing the population distribution of the biomarker in ITP and the application isotope ratio mass spectrometry (IRMS) as a confirmatory procedure. This has been applied successfully using the steroidal module of the ABP and GC-IRMS.
In addition to steroidal hormones, several other prohibited compounds may benefit from a similar approach. We intend to investigate the application of IRMS coupled to liquid chromatography to the confirmation of compounds that because of their physicochemical properties cannot be analyzed by GC and for which a definiticive confirmation procedure does not exist.
The analysis of AICAR by GC-C-IRMS has been described after silylation and its comparison with a steroid (pregnanediol) as an endogenous reference compound (ERC). The current limitations of this approach can be overcome by the use of LC-IRMS, allowing the underivatized compound analysis and the use of an ERC closer to its metabolic path.
The main 2-phenethylamine and octopamine target analytes are excreted as sulfates, whose hydrolysis is not obvious. The confirmation by GC-C-IRMS is impaired by the high interaction with GC systems. The direct analysis of their sulfated conjugates by LC-IRMS will unambiguously confirm their origin. The main objective is to prove the applicability for antidoping purposes of LC-IRMS in the analyses of intact sulfates.
For IGF-1 the main objective is the use of LC-IRMS for the analysis of recombinant preparations and preparations of human origin, to prove its applicability for anti-doping purposes. The protein will be analyzed intact or after trypsin digestion.