Detection and quantification of common beta2-agonists after inhaled administration in humans with dried blood spots and dried plasma spots

Code: 21A13GJ

Beta2-agonists salbutamol, formoterol, terbutaline and salmeterol delivered by inhalation are among the most used medications in athletes for treating asthma and exercise induced bronchoconstriction. To prevent supratherapeutic misuse that could result in performance enhancing effects, maximum permitted doses have been introduced for salbutamol and formoterol which are enforced through a urine threshold that corresponds to the maximum permitted dose. However, urine concentrations can be affected by a range of factors such as hydration status and urine production leading to large variations in urine concentrations of drug, both inter-patient, and intra-patient, which makes refining the urine threshold difficult. An alternative approach for quantifying beta2-agonist doping is measurement of concentrations using dried blood spots and dried plasma spots. These are easily conducted via finger prick, require no specialized personnel, are minimally invasive, and easily shipped to laboratories due to their light weight. The present project aims to investigate the utility of dried blood spots and dried plasma spot approaches for the measurement of systemic concentrations of the commonly used beta2-agonist salbutamol, formoterol, terbutaline, and salmeterol. Subjects will inhale beta2-agonists while exercising over a 1.5 h period with repeated sampling. Blood concentrations of beta2-agonists will be measured by dried blood spots and validated against traditional venous blood and urine concentrations. It is hoped that dried blood spots and dried plasma spots will avoid the variability traditionally associated with urine concentrations and help refine the detection of supratherapeutic dosing of beta2-agonists.