Trace Level Determination of Three Genotoxic Impurities in Drug Samples of Rizatriptan Benzoate by Liquid Chromatography-Tandem Mass Spectrometry

Abstract

A rapid, sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/ MS) method was developed and validated for the trace analysis of three potential genotoxic impurities in rizatriptan benzoate drug sample. LC-MS/MS analysis of these impurities was done on symmetry C-18 (100 mm x 4.6 mm, 3.5 μm) column. In this method, 0.2% formic acid was used as mobile phase A and mixture of methanol and acetonitrile (5:95, v/v) used as mobile phase B in gradient mode with the flow rate of 0.8 mL/min. The method was developed with the short run time of 12 minutes. Triple quadrupole mass detector coupled with positive electrospray ionization was used for the quantification of genotoxic impurities in multiple reaction monitoring (MRM) mode. The method was linear in the range of 2.97 ppm to 74.16 ppm for N-(3-chloropropyl)-N,N- dimethylamine (CDA), 3.02 ppm to 75.44 ppm for l-(4-hydrazinophenyl) methyl-l,2,4-triazole (HMT) and 3.02 ppm to 75.52 ppm for l-(4-nitrophenyl) methyl-1,2,4-triazole (NMT) with a correlation coefficient not less than 0.9995. The accuracy of the method was in the range of 92.75% to 102.49% for all three potential genotoxic impurities (PGIs). No impurities were identified in the rizatriptan benzoate active pharmaceutical ingredient sample. This method is able to quantify the impurities at very low levels.