Discrimination of prohibited oral use of salbutamol from authorized inhaled asthma treatment

Background: The administration of salbutamol is permitted only by inhalatio n by the international Olympic Committee (IOC) for the management of asthma and exercise-induced asthma in athletes. The establishment of criteria to distinguish between the IOC authorized use (inhaled) and the IOC prohibited use (oral) of salbutamol appeared possible using simultaneous evaluation o f variables based on the concentration of nonconjugated enantiomers of salb utamol excreted in urine. Methods: Urine was collected from asthmatic and nonasthmatic swimmers who h ad received various preexercise doses of oral (five doses of 4 mg) or inhal ed (two doses of 100 mu g) salbutamol. Urine was also obtained from subject s who had received the maximum dosage of inhaled salbutamol advisable for c ompeting athletes to provide protection from exercise-induced asthma and tr eatment of asthma (1600 mu g in 24 h, 800 mu g being in the last 4 h), All samples were analyzed to determine the total amount of unchanged salbutamol excreted in urine and the ratio between the S and R enantiomers. Results: The discriminant function D = -3.776 + 1.46 x 10(-3) {[S(+)] + [R( -)]} + 1.012 {[S(+)]/[R(-)]} can be used to classify data into two groups, inhaled and oral. The confirmatory criterion suggested (cutoff at D = 1.06, 4 SD from the mean D value of the inhaled distribution) has been verified in different sets of samples showing suspicious concentrations by conventio nal screening procedures in doping control. An 11.8% false-negative (oral c lassified as inhaled) rate is assumed with the confirmatory criterion propo sed, but virtually no false positives (inhaled classified as oral) are obta ined (<1 in 33 000). Conclusions: The overall procedure recommended is to screen all samples and to apply the confirmation criterion proposed to samples showing free racem ic salbutamol concentrations >500 9 mu g/L by gas chromatography-mass spect rometry or free + conjugated racemic salbutamol concentrations >1400 mu g/L by ELISA. (C) 2000 American Association for Clinical Chemistry.