Given the recent post from FDA on ‘possible mitigation strategies to reduce the risk of nitrosamines’ …
These nitrosamine drug substance-related impurities (NDSRIs) are a class of nitrosamines sharing structural similarity to the API. NDSRIs can be generated during manufacturing or during the shelf-life storage period of the drug product. In some cases, the root cause of NDSRI formation has been attributed to nitrite impurities present in excipients at parts-per-million amounts.1 Nitrite impurities have been observed in a range of commonly used excipients (as well as water) and may lead to the formation of NDSRIs in certain drug products.
Anyone developed standardized screening or quantitative methods for estimating nitrite impurities in excipients?
The problem is that based on the nitrosamine levels we need nitrite detection at the ppb rather than ppm level. The current methods are not reliable for routine screening which is what we would need but data is coming in suggesting that nitrites are pretty well ubiquitous.
Folks in Thermo have been busy… @Aaron published this morning an application note on “Determination of nitrite in pharmaceuticals”. Perhaps Aaron can help us by inviting Jingli Hu and Jeffrey Rohrer to discuss Challenges and perspectives about Nitrate testing!
