Abstract

FORCED DEGRADATION STUDY OF EMTRICITABINE FOR EVALUATION OF GENOTOXIC IMPURITY IN ACTIVE PHARMACEUTICAL INGREDIENT’S (API) SHELF LIFE

Anuj Prakash, Utpal Nandi, Anil K Teotia, Javed A. Farooqi* and GN Singh

ABSTRACT

Genotoxic impurities in drug substances or drug products are increasing concern to safeguard public health. Presence of genotoxic impurity in drug substances and drug products may be DNA reactive and posed significant problems for drug regulators and industry over the last decade. The principal concern relates to drug safety is the prolong exposure to compounds that can alter DNA, may ultimately produce a carcinogenicity. Therefore, the practical issue is that the conventional procedures should be there to identify DNA-reactive impurities in the shelf life of drug product. In the present study, emtricitabine, an antiretroviral agent is used to evaluate degradation pathways under different stress conditions in order to identify degradation products as prescribed by ICH guidelines. Emtricitabine was found to degrade mostly under acidic and oxidative conditions followed by formation of three major degradation products. The degradation products were identified by LC-MS to propose degradation pathways followed by evaluation of similarity with the structural alerts for genotoxic impurities specially methyl methanesulfonate and ethyl methanesulfonate.

Keywords: Emtricitabine; Forced degradation studies; LC-MS; Genotoxic impurity.