Abstract

Threshold substances are a delicate issue in anti-doping analysis. Especially for ephedrines, banned only "in competition" an inter-individual variability in metabolism and excretion can lead to sanction or not sanction the same behavior in different individuals. The use of these drugs, especially pseudoephedrine, is widespread among athletes, due to its decongestant action, but also for its stimulant activity. We noted an increase in the number of samples presenting with an elevated concentration (100 µg/ml and higher) of pseudoephedrine both in particular periods of the year, probably due to the typical seasonal diseases (allergic rhinitis, influenza), and, also, in correspondence of specific sport competitions. Due to the scarce literature data on this topic, we performed an observational study on 9 healthy volunteers taking different doses of over-the counter preparations containing pseudoephedrine for self-medication. At first, a method for quali-quantitative determination of ephedrines in urine was set up and fully validated, by an implementation of the method described by Forsdahl and Gmeiner, using as internal standards ephedrine-D3. The method has then been applied to observe the variability of concentrations of ephedrines/metabolites found in the urine samples of subjects taking these medications in therapeutic doses for self-medication (for the treatment of allergic rhinitis or against influenza symptoms) and, if so, at what administered dose the threshold value was exceeded, to verify whether a "population" threshold could discriminate between the administration of ephedrines for therapeutic uses and their administration with the aim of improving sport performance. In parallel to urine, the subjects involved in the study were hence required to give also oral fluid (OF) specimens, sampled every 1.5-2 hours. The results obtained confirm a high inter-individual variability in the urinary concentration of pseudoephedrine and cathine following the administration of the same therapeutic dose of preparation. The 5 µg/ml threshold for cathine can easily be exceeded after administration of therapeutic doses of pseudoephedrine in some subjects; in the same way, the proposed value of 100 µg/ml for pseudoephedrine can be exceeded. Furthermore, in many cases, the cut-off values are exceeded 8-12 hours after administration, when the substances are not more detectable in the corresponding oral fluid samples suggesting their not recent use. Aus dem Text