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

journal contribution
posted on 2023-05-18, 23:38 authored by Glenn JacobsonGlenn Jacobson, Hostrup, M, Christian NarkowiczChristian Narkowicz, David NicholsDavid Nichols, Eugene WaltersEugene Walters
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 µg (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 mean ± SD log (S):(R = .055 ± 0.025 (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 µg 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.

History

Publication title

Drug Testing and Analysis

Volume

9

Issue

8

Pagination

1262-1266

ISSN

1942-7611

Department/School

School of Pharmacy and Pharmacology

Publisher

John Wiley & Sons Ltd.

Place of publication

United Kingdom

Rights statement

Copyright © 2016 John Wiley & Sons

Repository Status

  • Restricted

Socio-economic Objectives

Other health not elsewhere classified

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