Various Analytical Techniques used for Nitrosamine impurities in Pharmaceutical Dosage Forms: A Comprehensive Review

Nitrosamine impurities are a class of substances formed from the reaction of a nitroso compound and secondary or tertiary amines under acidic conditions. The detection of nitrosamine impurities in Active Pharmaceutical Ingredients (APIs) and Finished Pharmaceuticals (FP) has raised significant health concerns due to their potent genotoxic carcinogenic properties. The presence of low concentration levels of nitrosamine impurities has led to drug withdrawals and extensive investigations into their formation. For the estimation of such low level of impurities led to development of highly sensitive and selective analytical methods for the simultaneous determination and quantification of various nitrosamine impurities in active pharmaceutical ingredients (APIs) and Finished Pharmaceuticals (FP). This review evaluates common analytical techniques for nitrosamine impurities detection, including Gas Chromatography-Mass Spectrometry (GC-MS), Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) and Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). It compares their sensitivity, specificity, and practical applications, and discusses sample preparation methods such as Solid-Phase Extraction (SPE), Liquid-Liquid Extraction (LLE) etc. The choice of method depends on sample type, required sensitivity and as per regulatory expectation.