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

Abstract

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 ® (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), 20β-dihydroprednisolone (20βPRED) and 20α-dihydroprednisolone (20αPRED) in the total fraction (glucuroconjugated and free). Maximum concentrations were 266, 500, 350 and 140 ng/ml for PRED, PREDON, 20βPRED and 20αPRED, 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, 20βPRED and 20αPRED only show less than 20% conjugation.

Annual banned‐substance review: Analytical approaches in human sports drug testing 2020/2021

“…The review and proposal includes also recently published information, 106,107 but due to the still limited literature data, compound‐specific reporting levels concerned seven glucocorticoids only, while for all other drugs, the cut‐off of 30 ng/ml was recommended to remain in force until further data are available. Whether or not the suggested reporting levels for prednisone and prednisolone of 300 and 100 ng/ml, respectively, are compatible with therapeutic intranasal drug administrations might require further investigations in the light of a recently published study by Deventer et al, 104 who reported on urinary concentrations up to 500 and 266 ng/ml, respectively, observed following a recommended intranasal dose of 4.5 mg of prednisolone.…”

The 39th Manfred Donike workshop on doping analysis

“…For instance, the legitimate use of prednisolone via intranasal application was reported to result in urinary prednisolone and prednisone concentrations above relevant reporting levels. 9 Further, residuals of legitimately used veterinary drugs containing complexed meldonium were suspected to be occasionally present in milk, potentially resulting in findings of the drug in urine samples collected after consumption of that milk. 10 Also, the problem of dietary supplements containing prohibited substances with or without declaration still prevails, and thorough follow-up strategies are required 11 as well as updates of antidoping testing protocols and information on the metabolism of new drugs (e.g., hydrafinil 12 ) in order to provide comprehensive routine doping controls.…”