Identification, characterization, and high-performance liquid chromatography quantification of process-related impurities in vonoprazan fumarate.

High-performance liquid chromatography analysis of vonoprazan fumarate, a novel proton pump inhibitor drug revealed six impurities. These were identified by liquid chromatography with mass spectrometry. Further, the structures of the impurities were confirmed by synthesis followed by characterization by mass spectrometry, NMR spectroscopy, and infrared spectroscopy. On the basis of these data and knowledge of the synthetic scheme of vonoprazan fumarate, the previously unknown impurity was identified as 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methyldimethylamine, which is a new compound. The possible mechanisms by which these impurities were formed were also discussed. A high-performance liquid chromatography method was optimized in order to separate, selectively detect, and quantify all process-related impurities of vonoprazan fumarate. The presented method has been validated in terms of linearity, limits of detection, and quantification, and response factors and, therefore, is highly suitable for routine analysis of vonoprazan fumarate related substances as well as stability studies.

Stability-indicating reversed-phase HPLC method development and characterization of impurities in vortioxetine utilizing LC-MS, IR and NMR.

The current study reports the development and validation of a stability-indicating reversed phase HPLC method for the separation and identification of potential impurities in vortioxetine, a recently developed antidepressant. The structures of a new compound and four process-related impurities formed during the synthesis were characterized and confirmed by NMR, MS, and IR spectroscopy analyses. The most probable formation mechanisms of the impurities identified were proposed. Based on the characterization data, the new compound was proposed to be 1-[4-[(2,4-dimethylphenyl)thio]phenyl]-piperazine. In addition, an efficient chromatographic method was optimized to separate and quantify the impurities, which were obtained in the 0.05-0.75 µg/mL range. The developed HPLC method was validated with respect to accuracy, precision, linearity, robustness, and limits of detection and quantitation.