Beclomethasone: oral, inhaled, intranasal, and rectal studies to evaluate the minimum reporting level and the washout period after oral intake.

Code: 22C06RV

Discrimination criteria between allowed and prohibited routes of administrations is needed for glucocorticoids (GC). Recent studies have demonstrated that the criterion of discrimination needs to be compound specific and, for that reason, since 2022, new and ompound-specific minimum reporting levels (MRLs) have been established for some GC for which data of administration studies were available. This project will be focused on beclomethasone (BOH), and the objective will be to define the best marker of discrimination between allowed and prohibited administrations, to establish the MRL, and to define the washout period after forbidden administrations.

BOH is administered as beclomethasone dipropionate (BDP). Clinical studies consiting of administration of BDP to healthy volunteers using single oral or repeated intranasal or repeated inhaled doses and collection of urine samples at different time periods will be perfomed. First, the metabolic profile of BDP in urine will be studied. The metabolites of BDP described up to now in urine are beclomethasone 17-monopropionate and BOH; the occurence of other urinary metabolites will be studied using LC-MS/MS methods. Second, a LC-MS/MS procedure to measure BDP and the most important urinary metabolites will be developed and validated. Third, BDP and metabolites will be measured in the urines collected after oral, intranasal and inhaled administrations. Finally, the urinary excretion profiles after the different administration routes will be compared and the best marker of discrimination between allowed and forbidden administrations will be proposed. The comparison will also led to establish the most suitable MRL and the washout period required after oral administration.