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Development of ultra‐high performance liquid chromatographic method for the analysis of Elvitegravir degradation products

Chemical stability of pharmaceutical molecules is a matter of great concern as it affects the safety and efficacy of the drug product [1]. Impurities in pharmaceutical product are the unwanted chemical compounds that remain within the active pharmaceutical ingredient (API), or are formed during production process or by degradation of API [2]. In order to provide a safe use of drugs, it is necessary to know structure and origin of impurities. Impurities can be toxic and carcinogenic and they can cause side effects and affect the activity and stability of the drug product. Regulatory agencies are requiring strict drug quality control, constant monitoring and impurity profiling. The drug purity testing includes analytical methods aimed at detection, identification, structural characterization and quantitative determination of impurities. Elvitegravir (ELV) belongs to a novel class of anti‐retroviral agents, integrase strand transferase inhibitors, which inhibit the integrase enzyme and prevent the virus replication [3]. The chemical name of ELV (Figure 1.) is 6(3‐ chloro‐2‐fluorobenzyl)‐1‐ [(2S)‐1‐hydroxy‐3‐ methylbutane‐2‐yl]‐7‐ methoxy‐4‐oxo‐1, 4‐ dihydroquinoline‐3‐ carboxylic acid. A new simple and rapid stability indicating method for determination of impurities in ELV active pharmaceutical ingredient has been developed and validated using reverse phase ultra‐high performance liquid chromatography. The main peak of Elvitegravir from process and degradation impurities was successfully separated. DryLab software was used for optimizing chromatographic conditions: time gradient, column temperature and pH value of mobile phase. Degradation products caused by forced degradation were analyzed by LC‐ MS/MS coupled system. Possible ELV degradation pathways were predicted by analyzing obtained MS and MS/MS spectra.

Elvitegravir ; degradation products ; UPLC

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