Abstract

FORCED DEGRADATION STUDY OF LAMIVUDINE UNDER THE SCOPE OF GENOTOXIC IMPURITY

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

ABSTRACT

Genotoxic impurities in drug substances or drug products are growing concern to ensure safety of the public health. Genotoxic impurity present in drug substances and drug products may be DNA reactive and posed significant problems for drug regulators and industry alike 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, lamivudine, an antiretroviral agent is used to evaluate degradation pathways under different stress conditions in order to identify degradation products as prescribed by ICH guidelines. Lamivudine was found to degrade under acidic, basic and oxidative conditions followed by formation of four degradation products. The degradation products were separated and identified by LC-MS to propose degradation pathways followed by evaluation of similarity with the structural alerts for genotoxic impurities. Finally, characterization of the genotoxic impurity by FT-IR, NMR and LC-MS.

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