Simultaneous Quantitation of Three Genotoxic Impurities in Rizatriptan Benzoate Using Liquid Chromatography-Mass Spectrometry

Abstract

A selective, sensitive and high throughput Liquid Chromatography Mass Spectrometry method has been developed for simultaneous quantification of three genotoxic impurities in Rizatriptan Benzoate. Three genotoxic impurities of Rizatriptan Benzoate namely 1-(4-Nitrobenzyl)-1,2,4-triazol, 4-(1H-1,2,4-Triazol1-yl methyl) benzene amine and 4-Amino-1-(4-nitrobenzyl)-1,2,4-triazolium bromide were separated on Zorbax SB-CN (150 mm × 4.6 mm, 3.5 µm) column using 10 mM ammonium acetate as buffer and acetonitrile as organic modifier in gradient composition at the flow rate of 1.0 ml/ min. All the impurities exhibited linearity with correlation of coefficient value greater than 0.990. The method was validated over the concentration range of 5 µg/g-70 µg/g for all the three impurities according to ICH guidelines. The method was successfully applied for the determination of three genotoxic impurities in Rizatriptan Benzoate drug substances.