Budesonide use and misuse in sports: elimination profiles of budesonide and metabolites after intranasal, high‐dose inhaled and oral administrations

Budesonide (BUD) is a glucocorticoid (GC) widely used in therapeutics. In sports, the World Anti-doping Agency (WADA) controls the use of GCs, and WADA-accredited laboratories use a reporting level of 30 ng/mL for 6beta-hydroxy-budesonide (6betaOHBUD) to detect the systemic administration of BUD. In the present work, we examined the urinary excretion profile of 6betaOHBUD, BUD, and 16alpha-hydroxy-prednisolone (16alphaOHPRED) after intranasal (INT), inhaled (INH) (at high doses) and oral administrations in male and female volunteers. BUD was administered to healthy volunteers using INT route (256 mug/day for three days, n = 4 males and 4 females), INH route (800 mug/day for three days, n = 4 males and 4 females, and 1600 mug/day for three days, n = 4 males) or oral route (3 mg, n = 8 females). Urine samples were collected before and after administration at different time periods, and were analyzed by liquid chromatography-tandem mass spectrometry. 6betaOHBUD and BUD concentrations were very low after INT treatment (0.0-7.1 and 0.0-8.1 ng/mL, respectively), and higher after INH treatments (0.0-35.4 and 0.0-48.3 ng/mL, respectively). For 16alphaOHPRED, elevated concentrations were detected after INT and INH treatments (2.6-66.4 and 3.4-426.5 ng/mL, respectively). Concentrations obtained following oral administration were higher than after therapeutic administrations (2.8-80.6, 1.5-36.1, and 10.4-532.2 ng/mL for 6betaOHBUD, BUD, and 16alphaOHPRED, respectively). After all administrations, concentrations were higher in males than in females. Results demonstrated that 6betaOHBUD is the best discriminatory marker and a reporting level of 40 ng/mL was found to be the best criterion to distinguish allowed from forbidden administrations of BUD.