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Enantioselective disposition of (R)-salmeterol and (S)-salmeterol in urine following inhaled dosing and application to doping control


Jacobson, GA and Hostrup, M and Narkowicz, CK and Nichols, DS and Walters, EH, Enantioselective disposition of (R)-salmeterol and (S)-salmeterol in urine following inhaled dosing and application to doping control, Drug Testing and Analysis, 9, (8) pp. 1262-1266. ISSN 1942-7611 (2017) [Refereed Article]

Copyright Statement

Copyright 2016 John Wiley & Sons

DOI: doi:10.1002/dta.2131


Salmeterol (USAN, INN, BAN) is a long-acting beta2-adrenoceptor agonist (LABA) widely used in the treatment of airways disease. Although salmeterol is permitted via inhalation by athletes and supratherapeutic dosing may enhance performance, no urine threshold has been established by WADA. Salmeterol is a chiral compound consisting of (R)- and (S)-enantiomers, normally administered as racemic (rac-) mixture via inhalation. Levels of rac-salmeterol in urine are often below detectable levels and there is surprisingly little information regarding the enantioselectivity of salmeterol pharmacokinetics. In this study, subjects inhaled either 50 (n=6) or 200 g (n=4; generally regarded as maximum therapeutic dose) of salmeterol and urine was then collected for 24 hours and analysed by enantioselective UPLC-MS/MS. Maximum rac-salmeterol urine concentrations were obtained at 2 hours for both doses with medians of 0.084 ng/mL after the 50 μg dose and 2.1 ng/mL after the 200 μg dose, with an individual maximum of 5.7 ng/mL. Levels were detectable at 24 hours for both doses. Salmeterol displayed enantioselective pharmacokinetics, with a meanSD log (S):(R=.0550.025 (P<0.0001) equivalent to (S):(R) of 1.13. In conclusion, rac-salmeterol by inhalation exhibits modest enantioselectivity in urine following single dose administration and can be detected following a single 50 g dose for up to 24 hours after inhalation. The present findings are of relevance if a urine threshold limit is to be introduced for salmeterol on the list of prohibited substances. The application of an enantiomer ratio analysis may offer improved discriminatory detection capability for doping control analysis applications.

Item Details

Item Type:Refereed Article
Keywords:enantiomer, doping, pharmacokinetics, LABA, chiral, beta2-agonist
Research Division:Biomedical and Clinical Sciences
Research Group:Pharmacology and pharmaceutical sciences
Research Field:Pharmaceutical sciences
Objective Division:Health
Objective Group:Other health
Objective Field:Other health not elsewhere classified
UTAS Author:Jacobson, GA (Associate Professor Glenn Jacobson)
UTAS Author:Narkowicz, CK (Dr Christian Narkowicz)
UTAS Author:Nichols, DS (Dr David Nichols)
UTAS Author:Walters, EH (Professor Haydn Walters)
ID Code:112499
Year Published:2017 (online first 2016)
Web of Science® Times Cited:11
Deposited By:Pharmacy
Deposited On:2016-11-14
Last Modified:2017-11-02

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