Quantification and In Silico Toxicity Assessment of Tazarotene and its Impurities for a Quality and Safe Drug Product Development.

Abstract

Tazarotene is internationally accepted common name for ethyl 6-[(4,4-dimethylthiochroman-6-yl)ethynyl]nicotinate. It is a synthetic retinoid used for the topical treatment of mild to moderate plaque psoriasis, acne vulgaris and photo aging. To ensure the quality of drug product and drug substance, a LC-MS compatible UHPLC method was developed for quantification of drug and its related substances. Stationary phase with fused core particle technology is used for the separation of impurities. Limit of quantification and limit of detection of the method are 0.1 and 0.03%, respectively. Precision of the method for Tazarotene and all its related substances is less than 2.2% RSD. The correlation coefficient is >0.999. Accuracy of method is ranged from 95.3% to 107.0%. Application of this method in stability analysis has been demonstrated by analyzing stressed samples. Experimental design is used for the verification of robustness of the method. To ensure the safety, an in silico toxicity of the drug and its related substances were determined using TOPKAT and DEREK toxicity predictions Both UHPLC and in silico methods were validated as per the ICH Q2 and ICH M7 guidelines, which will enable a rapid product development of Tazarotene topical formulations while ensuring the safety and quality of product.