The Quantitative Determination of Process Related Genotoxic Impurities in Esomeprazole Magnesium by GC-MS

A sensitive Gas chromatography-mass spectrometric (GC-MS) method is developed and validated for the determination of residuals 2-Chloromethyl-4-methoxy-3,5-dimethyl pyridine HCl (2), 2,3,5-Trimethyl pyridine Noxide (3), 4-Nitro-2,3,5-Trimethyl pyridine N-oxide (4) and 4-Methoxy-2,3,5-Trimethyl pyridine N-oxide (5) are genotoxic impurities in Esomeprazole magnesium (1) drug substance. Under the optimal conditions, the recovery for 2, 3, 4, and 5 are between 109.4% to 116.8%, 99.9% to 107.6%, 96.0% to 104.1%, and 87.4% to 105.2% for spiked samples at limits of quantification (LOQ) level in sample preparation. Limits of quantification (LOQ) and detection (LOD) are about 5 ppm and 1.5 ppm for the standard solutions of 2, 3, 4, and 5. The linearity values are 0.9989, 0.9968, 0.9988, and 0.9999 for 2, 3, 4, and 5. Based on these results, the method is applied to determine the residual genotoxic impurities are, 2-Chloro methyl-4-methoxy-3,5-dimethyl pyridine HCl (2), 2,3,5-Trimethyl pyridine Noxide (3), 4-Nitro-2,3,5-Trimethyl pyridine N-oxide (4) and 4-Methoxy-2,3,5-Trimethyl pyridine N-oxide (5) in Esomeprazole magnesium (1) drug substance.