M. Parr, J. Joseph
Feb 1, 2019
Citations
2
Influential Citations
85
Citations
Quality indicators
Journal
Journal of Pharmaceutical and Biomedical Analysis
Abstract
HighlightsN‐Nitrosodimethylamine (NDMA) in valsartan containing pharmaceuticals as impurity.Other drugs also found to contain NDMA in the late 1970–1980 s.Review of analytical methods for nitrosamine determination using different techniques for detection.Summary of appropriate sample preparation methods considering different matrices.Perspectives on relevance of general impurity testing for NDMA in drugs. Abstract Batch recalls for valsartan containing pharmaceutical products in July 2018 initiated a discussion on possible contaminations with N‐nitrosodimethylamine (NDMA). It appeared that NDMA was generated during synthesis of the active pharmaceutical ingredient (API) from the solvent dimethylformamide (DMF) and the reagent nitrite. Discussion on NDMA as API impurity is extended to other drugs since then. Already several years before scientific literature reported NDMA as impurity of several other drugs, thus underlining the apparent risk. At present none of the pharmacopoeias tests for NDMA and only very limited publications of methods for its determination in pharmaceuticals are published so far. This review summarizes aspects for the analyses of nitrosamines (NAs) with special focus on NDMA and discusses their potential applicability for drug analyses. The majority of recent publications utilize GC–MS or GC–MS/MS due to its high selectivity and low detection levels. GC‐TEA also provides high selectivity for nitrosamines. However, current availability of this combination is very limited. Alternatively, LC–MS/MS is also performed in NA analysis. An integration of a general test in future pharmacopoeias is suggested due to the toxicological relevance and broader spectrum of possible APIs that may be affected.