Quantitative analysis of nitrosamine impurities using liquid chromatography tandem mass spectrometry

Abstract Due to their potential carcinogenic and genotoxic effects on human health, nitrosamine impurities have become a significant concern for regulatory agencies globally. Thus, there is a need for highly sensitive and specific analytical methods capable of detecting trace levels of nitrosamines. Liquid chromatography tandem mass spectrometry (LC-MS/MS) has become the method of choice for identifying and quantifying these impurities due to its unparalleled sensitivity, selectivity, and precision. Regulatory bodies such as the United States Food and Drug Administration, European Medicines Agency, International Council for Harmonisation, and World Health Organization emphasize the importance of addressing nitrosamine hazards, providing updated guidance to manufacturers and applicants. The key objective of this review is to examine recent advancements in LC-MS/MS methods for nitrosamine analysis, focusing on detection limits, precision, accuracy, and matrix effects to ensure highly sensitive and specific detection of these potentially carcinogenic impurities in compliance with global regulatory guidelines.