Elimination Profile of Deflazacort and Metabolites in Urine and Plasma Following Oral Administration: Relevance to...

Deflazacort (DEF) is a glucocorticoid prohibited in sports competitions when orally administered. This study aimed to assess the urinary and plasma excretion profiles of DEF and its metabolites after a single oral administration to verify the World Anti-Doping Agency's minimum reporting level (MRL) of 30 ng/mL to detect administration of DEF. DEF was orally administered to eight healthy male participants (30 mg). Urine and plasma samples were collected before and after administration, and DEF and its metabolites were quantified using liquid chromatography-tandem mass spectrometry. Urinary concentrations confirmed that DEF is rapidly metabolized to 21-desacetyl-deflazacort (DES), with minimal detection of unchanged DEF. DES and the 6-hydroxy metabolites, 6βOHDES and 6αOHDES, were present in most urine samples during the first 48 h post-administration. DES peaked early (0-4 h) and declined below 30 ng/mL after 24 h, while 6βOHDES peaked later (4-8 h) and remained above 30 ng/mL until 36-48 h. 6αOHDES was detected at lower concentrations and cleared rapidly. In plasma, DES and 6βOHDES were detected within 8 h, with DES showing higher peak levels and longer half-life. DEF itself was not detected in plasma. Pharmacokinetic modeling showed good agreement between urinary and plasma excretion data. Cortisol levels were suppressed post-dose, indicating systemic GC activity, but recovered by 72 h in most subjects. The findings support the use of DES as the primary urinary marker for DEF detection, confirm the suitability of the MRL of 30 ng/mL and support the recommendation of a 3-day washout period due to interindividual variability.