IDENTIFICATION, CHARACTERIZATION OF DEGRADATION COMPONENT IN DESOXIMETASONE PHARMACEUTICAL DOSAGE FORMS AND ITS QUANTIFICATION IN THE PRESENCE OF PROCESS RELATED IMPURITIES

Abstract

A single, short, and stability-indicating reverse phase liquid chromatographic method has been developed for the simultaneous determination of desoximetasone as well as its related substances in its three pharmaceutical dosage forms. A major impurity was enhanced during accelerated and long term stability studies of desoximetasone gel and cream dosages. Forced degradation studies (or stress studies) under various conditions recommended by International Conference on Harmonization (ICH) were carried out to elucidate the inherent stability characteristics of active substance. The major degradant was identified by using LC-MS, FTIR, and 1H/13C NMR spectral analysis. A novel degradation mechanism was proposed, which should ease the pharmaceutical development of drug products containing desoximetasone. The chromatographic conditions were optimized using the impurity spiked solution and the samples generated from forced degradation studies. The chromatographic separation was achieved on a C18, 75 mm × 4.6 mm, 3.5 µm column with a linear gradient elution. The detection wavelength was at 240 nm. The stress samples were assayed against a qualified reference standard and the mass balance was found to be close to 99.6%. The developed RP-LC method was validated with respect to linearity, accuracy, precision, and robustness.