Abstract
In this study the solvolysis of novel fluocinolone acetonide 21-(2′-phenoxypropionate) in comparison with fluocinonide was analyzed in order to evaluate this process as an in vitro model for prodrug activation. The solvolysis was performed in ethanol:water (90:10 v/v) mixture using the excess of NaHCO3. The solvolytic mixtures of those esters with different lipophilicity were assayed by proposed RP-HPLC method using isocratic elution with methanol:water (75:25 v/v); flow rate 1 mL min−1, and detection at 238 nm. Solvolytic rate constants (at 25°C) for novel prodrug fluocinolone acetonide 21-(2′-phenoxypropionate) (0.0434 h−1) and fluocinonide (0.0593 h−1) have been compared. This in vitro model of solvolysis and corresponding rate constants are in good correlation with our preliminary data of anti-inflammatory potencies of those prodrugs. Limits of detection, important for the initial stage of solvolysis, were experimentally determined with values of 4.10 μM and 0.24 μM for fluocinolone acetonide 21-(2′-phenoxypropionate) and fluocinonide, respectively.
ACKNOWLEDGMENTS
This work was partially supported by the Ministry of Education and Science, Belgrade, Serbia, as part of Project No. 172041.