Investigation of the urinary excretion of prednisolone and metabolites after nasal administration : relevance to doping control

Glucocorticosteroid use in sport is restricted to non-systemic (nasal/ophtamological/dermatological/intra-articular) use. Systemic use is prohibited because of strong inflammatory suppressing effects. Prednisolone is a GC proven to be very effective in the treatment of nasal congestions and allergic rhinitis and its therapeutic use is allowed. To establish normal urinary concentration ranges for nasally administered prednisolone, an excretion study was performed with Sofrasolone (R) (nasal-inhaler). Six volunteers were administered a high dose (4.5 mg prednisolone in four gifts over a 9-h period). Samples were analysed using a validated LC-MS/MS method monitoring prednisolone (PRED) and the metabolites prednisone (PREDON), 20 beta-dihydroprednisolone (20 beta PRED) and 20 alpha-dihydroprednisolone (20 alpha PRED) in the total fraction (glucuroconjugated and free). Maximum concentrations were 266, 500, 350 and 140 ng/ml for PRED, PREDON, 20 beta PRED and 20 alpha PRED, respectively. These results show that the current reporting limit of 30 ng/ml in urine can be easily exceeded after therapeutic use. Hence, to avoid false-positive findings related to nasal application, this limit should be increased. To investigate the degree of glucuronidation of PRED and its metabolites also the free fraction was investigated. This shows that PREDON has the highest glucuroconjugation (50%). PRED, 20 beta PRED and 20 alpha PRED only show less than 20% conjugation