This article describes a method for the detection and quantitation of cathine, pseudoephedrine, ephedrine, and methylephedrine in urine, using their deuterated analogues as internal standards and derivatization to form the corresponding trimethylsilyl derivatives after a simple liquid-liquid extraction. The study was designed to evaluate whether the urinary cutoff values set by the World Anti-Doping Agency for the banned ephedrines (cathine >5 microg/mL, ephedrine and methylephedrine >10 microg/mL) can be exceeded after the normal self-administration of common over-the-counter medicaments containing nonbanned ephedrines. The present method, after validation, has been applied on real urine samples obtained from 9 healthy volunteers taking different doses of over-the-counter preparations containing ephedrines. Results obtained from excretion studies show high interindividual differences in the urinary concentrations of both pseudoephedrine and cathine, not dependent on body weight or sex nor, in some instances, on the administered dose. The same typical therapeutic dose of pseudoephedrine (60 mg) produced a urinary concentration of more than 5 microg/mL for cathine and of more than 100 microg/mL for pseudoephedrine in 2 of 9 subjects only. When a dose of 120 mg was administered, cathine concentration exceeded 5 microg/mL in 4 of 7 subject, and also concentrations of pseudoephedrine above 100 microg/mL. After administration of 5 x 120 mg of pseudoephedrine (120 mg administered every 7 days for 5 weeks) to one of the subjects exceeding the urinary threshold values, the urinary concentration of cathine and pseudoephedrine exceeded 5 microg/mL (peak concentration 14.8 microg/mL) and 100 microg/mL (peak concentration 275 microg/mL), respectively. When the same subject took 180 mg of pseudoephedrine, the urinary concentration values were below 5 microg/mL for ephedrine and 100 microg/mL for pseudoephedrine. In the case of ephedrine administration in a sustained-release formulation containing 12 mg of ephedrine, 2 of 3 subjects exceeded the urinary cutoff value of 10 microg/mL. The high interindividual variability is still significant even if the urinary concentration values are adjusted by specific gravity and/or creatinine. These results confirm a high interindividual variability in the urinary concentration of ephedrines after the administration of the same therapeutic dose of a preparation.