Chromatographic Separation and Quantification of Nine Nitrosamine Genotoxic Impurities in a Single Method in Nebivolol Tablet by Using Validated Ultra-Sensitive Liquid Chromatography: Mass Spectrometry Analytical Method.

This article focuses on the development and validation of a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with atmospheric pressure chemical ionization (APCI) for simultaneous detection and quantification of nine nitrosamine impurities in nebivolol tablets. Nitrosamines, classified as Class 1 genotoxic impurities by the International Council for Harmonization (ICH), pose carcinogenic risks even at trace levels, necessitating highly sensitive analytical methods for pharmaceutical quality control. The validated method demonstrated specificity, accuracy, precision, linearity (r² > 0.99), and low limits of quantification (approximately 10–20 parts per billion), enabling reliable detection of nitrosamines well below regulatory limits. Application of the method to commercial nebivolol samples showed no detectable nitrosamine impurities, supporting its suitability for routine monitoring to ensure drug safety and compliance with regulatory standards.