Characterization of Elvitegravir and Its Related Impurities Using ESI–LC–MS, NMR Techniques, Method Development and Validation of Its Related Substances by HPLC Method

Abstract

Elvitegravir (ETV), drug substance, and its eleven process-related impurities have been identified and their structural identification study has been carried out with the aid of ¹H, ¹³C NMR, and ESI–LC–MS spectroscopic techniques. Plausible fragments were also proposed for each impurity to ascertain its structure. Simple, facile, and selective, stability indicating, mass spectrometry compatible HPLC method has been developed and subsequently validated with the validation parameters of specificity, LOD, LOQ, precision at LOQ, linearity, accuracy at LOQ to 120% levels, method precision, intermediate precision studies, and solution stability has also been established. This method encompasses a simple gradient mode of separation with mobile phases—(A) 0.1% trifluoroacetic acid in water and (B) 0.1% trifluoroacetic acid in acetonitrile, the mass sectrometric compatible mobile phase has been chosen for the identification of known, unknown and degradation impurities. To assess the nature of each impurity, whether they are either process-related or degradation-induced, an intensive stress study has also been conducted. From this degradation assessment, all the impurities have been classified as process-related. Further, the assessment of three different manufacturers samples was also executed to show the method applicability and comparison of quality of the different manufacturers drug, and thus this method shall be engaged as a quality inferring tool for the marketed sample.