부산대학교 도서관

Purpose: The presence of the impurity N-nitrosodimethylamine (NDMA) has been a reason for recent drug product recalls in 2019–2020.Methods: This document reviews the timing of ranitidine and valsartan recalls due to NDMA; the numerical values reported in the available literature are compared, while the proposed mechanisms and influencing factors are discussed in detail. The liability of other histamine H2 receptor antagonists such as famotidine and cimetidine is also investigated according to the information available in the literature.Results: The presence of nitrate ions, acidity of the environment, and nitrate contamination of the pharmaceutical excipients and temperature are effective factors in the production of this impurity. The effect of excipients is also discussed. Special attention is necessary to select the proper type of analytical method in examining trace amounts of this impurity in drug samples.Conclusion: The available data builds a case for the evaluation of NDMA formation in all histamine H2 receptor antagonists especially famotidine as a liable agent at different conditions and in the presence or absence of nitrite ions and some pharmaceutical excipients in vitro and in vivo. Special pharmaceutical formulation and manufacturing designs may be able to prevent the formation of this impurity.