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

Abstract

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 × 4.6 mm, 4 µm 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°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.

Effect of Different Skin Penetration Promoters in Halobetasol Propionate Permeation and Retention in Human Skin

“…This is the reason why a simpler, and easier methodology was developed, with less chemical reagents and at a low cost, in comparison to that provided by pharmacopoeia and other authors for the determination of HB [ 40 ]. Numerous methodologies have been described for the detection and quantification of HB in commercial formulations, including high performance liquid chromatography (HPLC), ultra performance liquid chromatography (UPLC) and spectrophotometric techniques [ 41 , 42 , 43 , 44 , 45 ], but so far, no methodology for the quantification of HB samples from ex vivo experimentation with biological tissues has been determined. The HPLC methodology for the determination of HB described by united states pharmacopoeia (USP) [ 40 ] uses gradient conditions.…”

“…In this work we have optimized the methodology described by the USP to perform the analysis of the samples in 7–8 min with an isocratic acetonitrile/water flow which is easier and eight times faster. HB is practically insoluble in water (Cs < 0.007 mg/mL) [ 46 ], and most of the techniques described for the determination of non-biological complex samples need pre-treatment, and have to be solubilized in water or a buffer, and this procedure could alter the drug stability [ 43 , 45 ]. Our analytical methods avoid these steps and their related difficulties.…”