Detection of urinary phase-I and phase-II metabolites of ephedrine and oxilofrine by LC-MS/MS

Stimulants are prohibited in sports by the World Anti-Doping Agency (WADA) for use in competition. Ephedrine acts indirectly sympathomimetic and has central stimulating properties. It is prohibited when its concentration in urine is higher than 10 µg/mL. Oxilofrine (p-OH-ephedrine) acts direct sympathomimetic on α- and β-receptors and has indirect sympathomimetic effects, too. Ephedrine is used therapeutically as decongestant in cold medicines whereas oxilofrine is used in the therapy of hypotony. N-Demethylated ephedrine has been described as main metabolite of ephedrine and was found in urine after oral uptake besides the unchanged drug. In addition, hippuric acid, benzoic acid and a metabolite resulting from oxidative desamination of the side chain are decribed as metabolites with lower incidence. Aromatic hydroxylation or excretion of phase-II metabolites are not yet reported. For oxilofrine a conjugated metabolite was described by Kauert et al. (1988), but it was not characterised in detail whether it is conjugated with sulfuric add or glucuronic acid. In the course of our investigations, two excretion studies were performed. Urine specimen were analyzed after uptake of ephedrine and oxilofrine, respectivley. The main focus of these studies was the identification and characterization of their metabolites with attention on the conjugated metabolites by the help of LC-MS/MS. Einleitung gekürzt