Threshold level for theophylline in doping analysis

HPLC in the reversed-phase mode is used to assay methylxanthines including theobromine, paraxanthine, theophylline and caffeine in urine. The calibration graphs show good linearity in the concentration range 0-10 mu g/ml. The limit for accurate quantitation of theophylline was 0.25 mu g/ml. Between 6 and 20% of the parent drug is recovered in urine (0-12 h) after the oral administration of sustained release preparations containing 150 and 250 mg theophylline to four volunteers. Theophylline levels above 0.25 mu g/ml were found in 1539 out of 3885 urine samples collected from athletes during unannounced doping control in Flanders. Statistical evaluation of the results gives a far outside value [75th percentile+(3x interquartile range)] of 2.25 mu g/ml. The ratio theophylline paraxanthine (TP/PX) as an indicator for the non-dietary intake of theophylline seems to be more reliable. The far outside ratio was 0.20. To ensure with the greatest possible degree of certainty that no false-positive result is reported, decision limits of 5 mu g/ml and 0.50, for theophylline and the ratio TP/PX respectively, are proposed.