Identification and quantitation of related substances of super potent steroid in its topical combination drug product with vitamin D3 analogue

Abstract

Clobetasol propionate is an internationally accepted common name for 21-chloro-9-fluoro-11beta,17-dihydroxy-16beta-methylpregna-1,4-diene-3,20-dione 17-propionate. The combination of calcipotriol (vitamin D3 analogue) and clobetasol propionate (super potent steroid) is being used as a topical formulation for the treatment of psoriasis from several years. In this work an ultra-high performance liquid chromatography equipped with photodiode array detector and a mass compatible mobile phase in a gradient elution is employed for the separation of five related substances in presence of calcipotriol and its two impurities with a last eluting impurity in less than 11 min. A simple and efficient sample extraction procedure was developed to achieve the highest sensitivity as of today with limit of detection (LOD) and limit of quantitation (LOQ) of 0.03 % and 0.10 % respectively as required by industry for drug product of clobetasol propionate and its combination products. Stationary phase with fused core particle technology is employed for the separation of impurities. Precision of the method is found to be less than 1.0 % RSD. The correlation coefficient is > 0.999. Accuracy of method is ranged from 93.3 % to 108.0 %. This is the first reported UHPLC method for the estimation of five related substances of clobetasol propionate in its combination product with calcipotriol.