Isolation, identification and characterization of novel process-related impurities in flupirtine maleate

•Two novel process-related impurities have been identified in flupirtine maleate bulk drug.•The two new impurities were isolated, identified, and characterized using HPLC, MS, 1H, 13C, 2D NMR and IR techniques.•Preparation and structure elucidation of a known impurity (impurity-III) were also first reported in this paper.

Flupirtine maleate is a centrally acting, non-opioid, nonsteroidal antiinflammatory analgesic. During the manufacturing of flupirtine maleate, two unknown impurities present in the laboratory batches in the range of 0.05–1.0% along with the known impurities in HPLC analysis. These unknown impurities were obtained from the enriched mother liquor by column chromatography. Based on the complete spectral analysis (MS, 1H, 13C, 2D NMR and IR) and knowledge of the synthetic scheme of flupirtine maleate, these two new impurities were designated as diethyl 5-((4-fluorobenzyl)amino)-2-oxo-1H-imidazo[4,5-b]pyridine-1,3(2H)-dicarboxylate (impurity-I) and diethyl(6-((4-fluorobenzyl)amino)pyridine-2,3-diyl)dicarbamate (impurity-II). Impurity isolation, identification, structure elucidation and the formation of impurities were also discussed. Preparation and structure elucidation of impurity-III were also first reported in this paper.

Graphical abstractIn this study, two novel process-related impurities (impurity-I and impurity-II) in flupirtine maleate bulk drug were isolated, identified, and characterized using HPLC (analytical), MS, 1H, 13C, 2D NMR and IR techniques. Besides, preparation and structure elucidation of a known impurity (impurity-III) were also first reported in this paper.Figure optionsDownload full-size imageDownload as PowerPoint slide