Low-Level Determination of Mutagenic Nitrosamine Impurities in Drug Substances by LC–MS/MS

Since the detection of N-nitrosodimethylamine (NDMA) in a batch valsartan 2018, at levels exceeding ICH acceptable intake limits for mutagenic impurities, analysis nitrosamines has become an intense focus point pharmaceutical industry. The identification and low-level determination potentially affected materials is challenging requires application highly sensitive analytical techniques. This article reviews chronological development story regulatory landscape that evolved. It will then discuss methods series referenced by authorities, demonstrating separation these compounds from active ingredient (API) looking how mass spectrometry (MS) can be applied to ensure required reached.