Development and Validation of Trace Level Quantification of Nine Azido Genotoxic Impurities in Losartan Potassium Active Pharmaceutical Ingredients by Liquid Chromatography‐Tandem Mass Spectrometry

ABSTRACT The objective of the study is to develop a sensitive and simple liquid chromatography‐tandem mass spectrometry for the determination of nine azido impurities in Losartan potassium active pharmaceutical ingredients. An advanced analytical method should be developed to determine these nine Azido impurities at 0.5 ppm level. Currently, no such method is reported to control these impurities in losartan potassium drug substance. The nine impurities separation was achieved using Hypersil ODS stationary phase with gradient elution and mobile phase of 0.1 M ammonium acetate as mobile phase A and methanol as mobile phase B. The developed method was found to be sensitive to the limit of detection and limit of quantitation levels as per the International Council for Harmonization M7 guidelines. The method was linear from 0.5 ppm to 15 ppm for all nine azido impurities. This is a single method for the simultaneous determination of all azido impurities in the presence of losartan potassium drug substance at 0.5 ppm and the same method used in the quality control laboratory for sample analysis.