LAUSR

Twenty-two pharmaceutical formulations containing prednisolone or prednisone commercially available in Italy, Belgium, Spain, Brazil, and India, were analyzed through a specific gas chromatography combustion isotope ratio mass spectrometry, GC-C-IRMS, method. All of them showed typical non-endogenous δ13 C values, except for the Belgian nasal spray, Sofrasolone®, with less depleted 13 C content (-17.84 ± 0.18 ‰). Observational studies were performed on two volunteers in therapy with Sofrasolone® to confirm the applicability of the method and suggest adequate interpretation criteria also in case of drugs with less negative δ13 C values. Urine samples were collected before, during, and within the 36 hours after the administration of the spray. Both δ13 C values and urinary concentrations of prednisolone and prednisone were evaluated. All samples were subjected to an adequate pre-treatment (enzymatic hydrolysis, liquid/liquid extraction, and two sequential HPLC steps) before the GC-C-IRMS instrumental injection, according to the method recently developed and validated in our laboratory. Pregnanediol (PD), tetrahydro-11-deoxycortisol (THS), and pregnanetriol (PT) were selected as endogenous reference compounds. The excretion profile was estimated through the liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) method routinely used for the quali-quantitative detection of glucocorticoids. δ13 C values and urinary levels of prednisolone and prednisone were also determined after the intake of one single vial of Sintredius®, a prednisolone oral formulation with conventional more negative δ13 C value (-29.28 ± 0.25 ‰). Finally, the potential masking effect that a combined therapy with Sofrasolone® and Sintredius® could induce on the IRMS findings was investigated.