Following the valsartan scandal in 2018, the testing of drug substances and drug products for N-nitrosamines has become a critical and mandatory quality control measure. The European Pharmacopoeia chapter 2.5.42 currently describes three analytical methods for this purpose: HPLC–MS/MS, GC–MS, and GC–MS/MS. The US Pharmacopeia monograph 〈1469〉 adds four other methods, LC–high-resolution mass spectrometry (HRMS), headspace GC–MS, LC–MS/MS, and GC–MS/MS. In addition, our group has developed a universal method on the basis of supercritical fluid chromatography (SFC), capable of separating 16 different N-nitrosamines within just 4 min. These eight methods differ significantly in terms of sustainability, with particular emphasis on the reagents used, the separation techniques employed, and their performance characteristics. When assessing the sustainability of such analytical methods, it is essential to consider not only ecological but also economic factors.
