Abstract: Objective To establish an LC-HRMS method for the determination of NDMA genotoxic impurities of analogs of ranitidine substances and products. Methods The separation was carried out on a C₁₈ column (100 mm×4.6 mm, 3 μm) by liner gradient elution using 0.1% formic acid as mobile phase A and 0.1% formic acid acetonitrile as mobile phase B. The HRMS determination of NDMA was conducted by means of positive electrospray ionization parallel reaction monitoring using the internal reference method. Results Linear calibrations were established for NDMA in the range of 0.5 to 100 ng·mL^-1. The limits of detection and quantification proved to be as low as 0.3 and 0.5 ng·mL^-1 respectively. The average recoveries were between 82.9% and 119.2%. The content of NDMA in the 10 samples detected with this method ranged from 0.000 002% to 0.000 014%. Conclusion The established LC-HRMS method has been validated to be suitable for the simultaneous quantitative determination of NDMA genotoxic impurities in ranitidine.

Key words: ranitidine hydrochloride, NDMA, HRMS, genotoxicity