A simple, sensitive, and straightforward LC–MS approach for rapid analysis of three potential genotoxic impurities in rabeprazole formulations

Abstract

In the present study, a sensitive and fully validated liquid chromatography with mass spectrometry method was developed for the quantification of three potential genotoxic impurities in rabeprazole drug substance. The separation was achieved on Symmetry C18 column (100×4.6mm, 3.5μm) using 0.1% formic acid in water as mobile phase A and acetonitrile as mobile phase B in gradient elution mode at 0.5mL/min flow rate. Triple quadrupole mass detection with electrospray ionization was operated in selected ion recording mode for the quantification of impurities. The calibration curves were demonstrated good linearity over the concentration range of 1.0-4.5ppm for O-phenylenediamine, 1.8-4.5ppm for 4-nitrolutidine-N-oxide and 1.0-4.5ppm for benzyltriethylammonium chloride with respect to 10mg/mL of rabeprazole. The correlation coefficient obtained in each case was >0.998. The recoveries were found satisfactory over the range between 94.22 and 106.84% for all selected impurities. The method validation was carried out following International Conference on Harmonization guidelines, from which the developed method was able to quantitate the impurities at 1.0ppm for O-phenylenediamine, 1.8ppm for 4-nitrolutidine-N-oxide and 1.0ppm for benzyltriethylammonium chloride. Furthermore, the proposed method was successfully evaluated for the determination of selected impurities from bulk drug and formulation samples of rabeprazole within the acceptable limits.