N-Nitrosation in the absence of nitrosating agents in pharmaceuticals?

A fantastic reflection on the chemistry of Nitrosamines Impurities. Published by Jires et al. “N-Nitrosation in the absence of nitrosating agents in pharmaceuticals?”

Access here: N-Nitrosation in the absence of nitrosating agents in pharmaceuticals? - ScienceDirect

2 Likes

The addition of Na2CO3 into the tablets during manufacture resulted in tablets without NDMA (NDMA < LOQ) even in batches spiked with both dimethylamine and H2O2. Thus, adjusting the pH of the solid dosage forms remains a sufficient measure of controlling N-nitrosamines in the product, even in products with limit amounts of oxidating agent (H2O2) and N-nitrosation precursor (dimethylamine).

3 Likes

FDA mentions the addition of bases such as Na2CO3 is effective to prevent nitrosation in the mitigation approach. It’s reasonable. The excerpt is as follows;

A second possible approach is based upon the fact that the formation of nitrosamines typically occurs under acidic conditions, whereas, in a neutral or basic environment, the kinetics of these reactions are significantly reduced. Thus, formulation designs that incorporate excipients such as sodium carbonate that modify the micro-environment to neutral or basic pH, should in principle inhibit the formation of NDSRIs. Each manufacturer should determine the potential benefit from and demonstrate the suitability of any reformulation approach.

1 Like