Impurity Profiling and a Stability-Indicating UPLC Method Development and Validation for the Estimation of Related Impurities of Halobetasol Propionate in Halobetasol Propionate 0.05% (w/w) Cream

Abstract

A simple, short and stability-indicating reverse phase-ultra-performance liquid chromatography method was developed and validated for the quantitative determination of related impurities of halobetasol propionate in halobetasol propionate 0.05% cream formulation. The proposed method was developed on an ACQUITY UPLC™ BEH Phenyl (2.1 × 100 mm, 1.7 µm) column at 40°C with a mobile phase containing a gradient mixture of potassium hydrogen phosphate buffer and acetonitrile and methanol as modifiers with a runtime of 13.0 min at a monitored wavelength of 242 nm. A simple preparative method and liquid chromatography-mass spectrometry-compatible UPLC method also were developed for the isolation and identification of impurities and degradation products. The drug was subjected to forced-degradation conditions and found to degrade significantly. The stability-indicating capability of the developed method is established by analyzing forced-degradation samples in which the spectral purity of halobetasol propionate is ascertained along with the separation of degradation products from the analyte peak. The developed method was validated as per International Conference on Harmonization guidelines. The developed method is precise (%relative standard deviation <2.0) and is capable of detecting and quantifying all the six impurities at a level of 0.01 and 0.03%, respectively, with respect to test concentration. The wide linearity range, sensitivity, accuracy, short retention time and simple mobile phase imply that the method is suitable for routine quantification of halobetasol propionate and its related substances.

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.…”

A Mini-review on Ultra Performance Liquid Chromatography

“…Determination of products and process impurities of asenapine maleate in asenapine sublingual tablets by UPLC 57 . c) Impurities of halobetasol propionate in cream 58 .…”

A Review: Recent Trends in Analytical Techniques for Characterization and Structure Elucidation of Impurities in the Drug Substances

“…The main reason to couple the capillary zone electrophoresis with the mass spectroscopy technique is that the ideal separation power of the capillary electrophoresis (CE) has been achieved whereas; mass spectra will provide sufficient structural information. There should be a high grade of orthogonality between the methods during the separation of impurity, to accomplish better resolution of separated impurities [60][61][62][63][64][65] . Different techniques for impurity profiling, include coupling of CE with varying MS ionization systems such as electrospray ionization (ESI-MS), atmospheric pressure chemical ionization (APCI-MS), atmospheric pressure photoionization (APPI-MS) and thermospray ionization (TSI-MS).…”