A Rapid, Selective and Sensitive Electrospray Ionization Assisted LC-MS Method for Ranolazine and Identification of Its Two Potential Genotoxic Impurities

Abstract

A rapid, sensitive and selective electrospray ionization liquid chromatography-mass spectrometry (LC-MS) approach was developed to find and quantify the two genotoxic RANO contaminants (A and G) and forced degradation products of RANO in formulations of pharmaceutical drugs. X Select CSH C18 (100 x 3.0 mm, 2.5 μm) instrument was utilized for the separation with mobile phase containing of ammonia solution (A) and methanol (B) in gradient elution. About 254 nm as detection wavelength and 0.3 mL/min as flow rate were maintained. RANO has been degraded under stress conditions like thermal, oxidative, hydrolytic, peroxide, photolytic, acid and base, conditions. The resultant RANO products of degradation were well separated from RANO and its contaminants. Based on ICH rules the validation process was complying with the acceptance of precision, linearity, robustness and accuracy. To quantify the constituent contaminants (A and G), a positive electrospray ionization was connected to a triple quadrupole mass detector. The contaminants were determined in terms of LoD and LoQ values of 0.075 and 0.25 ppm, respectively, using the multiple reaction monitoring (MRM) mode.