DETECTION OF NITROSAMINE IMPURITIES IN SARTAN DRUG PRODUCTS BY GC-MS

Abstract

Since the 2018 recalls of valsartan, nitrosamine impurities in sartan drug substances and tablets have been a major quality and regulatory concern. This review summarises published work on detecting these impurities by gas chromatography-mass spectrometry (GC-MS), and it reports no new data. It describes how the impurities arise in tetrazole-ring synthesis, the toxicological basis of the acceptable intake limits, sample preparation and injection options, chromatographic and mass spectral conditions, and validation. The literature shows that headspace and direct-injection GC-MS can reach the sensitivity required, though artefact formation, matrix effects and limited reporting of validation detail complicate comparison between laboratories.