Reducing False Negative Reporting: Discrimination of Prohibited Administration of Levosalbutamol from Non-Prohibited Inhalation of Racemic Salbutamol

Code: 23A05MP

According to current WADA regulations the application of levosalbutamol, i.e. a single enantiomer of salbutamol (in any dosage form) is prohibited (class S3, beta-2-agonists). In contrast, the use of the more common racemic salbutamol (mixture of the two mirror-images of salbutamol) is considered as non-prohibited after inhalation of doses not exceeding 600 micrograms over 8 hours (1600 micrograms over 24 hours). At present, a threshold for the urinary salbutamol (excreted unchanged or as glucuronide) is set in doping control samples for discrimination of therapeutic and non-therapeutic use of salbutamol. With currently applied methods used in doping control laboratories a separation of the two mirror images is impossible. Hence, a discrimination of salbutamol and levosalbutamol is not performed and the concentration cut-off may result in a false negative classification of an adverse analytical finding after administration of levosalbutamol. The project aims to provide data from the urinary elimination of levosalbutamol and compare it with data obtained after inhalation of salbutamol. As the sulfoconjugate represents the major metabolite, it will be included in the set of target analytes besides the combined parent compound and glucuronide that are considered for the current threshold concentration. Chiral chromatography will be also applied to evaluate its value for potential discrimination. Thus method optimization and validation will be needed in advance to provide reliable data. The reference material of salbutamol-sulfoconjugate was synthesized by the project team already and will be used for method performance characterization. Finally, the method may be transfered to the doping control laboratories after successful completion of the project.