Simultaneous and Trace Level Quantification of Five Potential Genotoxic Impurities in Ranolazine Active Pharmaceutical Ingredient Using LC-MS/MS

摘要

Highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the simultaneous determination of five potential genotoxic impurities in ranolazine active pharmaceutical ingredient. Chromatographic separation achieved using Poroshell C18 PFP 150 × 3.0 mm 2.7 μ column and 0.1% formic acid in water as Mobile phase A and 0.1% formic acid in methanol as mobile phase B using gradient elution and a flow rate of 0.4 ml/min with a run time of 18 minutes. Mass spectrometric conditions were optimized using electrospray ionization in positive mode. Method shows excellent linearity from 0.05 - 5.0 ppm of the ranolazine test concentration for all the five impurities. The correlation coefficient was observed greater than 0.99. Satisfactory recoveries were observed for all the five impurities within the range of 102.9% - 112.3%. Method has been validated as per ICH recommended guidelines with a LOQ of 0.15 ppm achieved. The developed method was able to quantify all the five impurities at a concentration level of 1 ng/ml (0.5 ppm with respect to 2 mg/ml ranolazine).