HPLC evaluation of solvolysis of a novel ester fluocinolone acetonide 21-(2'-phenoxypropionate) in comparison with fluocinonide

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 degrees 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 mu M and 0.24 mu M for fluocinolone acetonide 21-(2'-phenoxypropionate) and fluocinonide, respectively.