Quantification of Halobetasol Propionate and Its Impurities Present in Topical Dosage Forms by Stability-Indicating LC Method

A novel, sensitive, stability-indicating, gradient, reverse-phase high-performance liquid chromatographic method has been developed for quantitative determination of halobetasol propionate and its impurities in topical dosage forms. The chromatographic separation was achieved on a Phenomenex Synergi polar reverse phase, 250 x 4.6 mm, 4 mu m column. Mobile phase A comprises a mixture of 0.01 M KH2PO4 buffer containing 0.2% 1-octane sulfonic acid sodium salt (pH 3.0), acetonitrile and methanol in the ratio 80: 15: 05 (v/v/v), respectively, and mobile phase B contains a mixture of 0.01 M KH2PO4 buffer containing 0.2% 1-octane sulfonic acid sodium salt (pH 3.0), acetonitrile and methanol in the ratio 20: 70: 10 (v/v/v), respectively. The flow rate is 0.8 mL min(-1). The column compartment temperature is set at 40 degrees C and the detection wavelength is set at 240 nm. The resolutions between Halobetasol propionate and all the impurities are >2.0 for all pairs of compounds. The drug product was subjected to International Conference on Harmonization (ICH)-prescribed hydrolytic, oxidative, photolytic and thermal stress conditions. The method is validated as per the ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision, robustness and ruggedness.