title: Beta2-Agonist Doping Control and Optical Isomer Challenges.
abstract: The World Anti-Doping Agency (WADA) currently allows therapeutic use of the beta2-agonists salbutamol, formoterol and salmeterol when delivered via inhalation despite some evidence suggesting these anti-asthma drugs may be performance enhancing. Beta2-agonists are usually administered as 50:50 racemic mixtures of two enantiomers (non-superimposable mirror images), one of which demonstrates significant beta2-adrenoceptor-mediated bronchodilation while the other appears to have little or no pharmacological activity. For salbutamol and formoterol, urine thresholds have been adopted to limit supratherapeutic dosing and to discriminate between inhaled (permitted) and oral (prohibited) use. However, chiral switches have led to the availability of enantiopure (active enantiomer only) preparations of salbutamol and formoterol, which effectively doubles their urine thresholds and provides a means for athletes to take supratherapeutic doses for doping purposes. Given the availability of these enantiopure beta2-agonists, the analysis of these drugs using enantioselective assays should now become routine. For salmeterol, there is currently only a therapeutic dose threshold and adoption of a urinary threshold should be a high priority for doping control.
authors.affiliation: School of Medicine, University of Tasmania, Private Bag 26, Hobart, TAS, 7001, Australia. glenn.jacobson@utas.edu.au.
authors.forename: Glenn A
authors.initials: GA
authors.lastname: Jacobson
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, New Zealand.
authors.forename: J Paul
authors.initials: JP
authors.lastname: Fawcett
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000652:urine; D000420:Albuterol / Q000008:administration & dosage* / Q000652:urine; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy; D056352:Athletes; D004300:Doping in Sports / Q000331:legislation & jurisprudence / Q000517:prevention & control*; D000068759:Formoterol Fumarate / Q000008:administration & dosage* / Q000652:urine; D006801:Humans; D000068299:Salmeterol Xinafoate / Q000008:administration & dosage* / Q000652:urine
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D018927:Anti-Asthmatic Agents; D000068299:Salmeterol Xinafoate; D000420:Albuterol; D000068759:Formoterol Fumarate