Nitrosamine risk assessment of Active Pharmaceutical Ingredients (APIs) reveals that not all APIs containing an amine functional group are equally susceptible to nitrosamine formation. Specifically, secondary amines and dimethyl tertiary amines are structures of concern. In contrast, tertiary amines are generally not considered high-risk because their steric hindrances and instability reduce their potential for nitrosation and primary amines due to their reactivity. Additionally, the stability of an amine group can be significantly influenced by its hybridization; if the amine group is part of a hybridized orbital—such as when it is double-bonded to an alpha-carbon—this configuration stabilizes the amine group and lowers the likelihood of reactions that could lead to nitrosamine formation. Furthermore, amines that are immediately adjacent to a carbonyl group (carboxamides) are not seen included in the FDA’s list of at-risk substances. Possibly the electron-withdrawing properties of carbonyl groups, significantly decrease the reactivity of adjacent amines, thereby mitigating the risk of nitrosamine formation. By evaluating APIs using these criteria, one can more accurately assess the risk of nitrosamine impurities
Also Refer: A new framework for identifying nitrosamine risks (Adare Pharma Solutions)
Nitrosamine risk assessment of Active Pharmaceutical Ingredients (APIs) reveals that not all APIs containing an amine functional group are equally susceptible to nitrosamine formation. Specifically, secondary amines and dimethyl tertiary amines are structures of concern. In contrast, tertiary amines are generally not considered high-risk because their steric hindrances and instability reduce their potential for nitrosation and primary amines due to their reactivity. Additionally, the stability of an amine group can be significantly influenced by its hybridization; if the amine group is part of a hybridized orbital—such as when it is double-bonded to an alpha-carbon—this configuration stabilizes the amine group and lowers the likelihood of reactions that could lead to nitrosamine formation. Furthermore, amines that are immediately adjacent to a carbonyl group (carboxamides) are not seen included in the FDA’s list of at-risk substances. Possibly the electron-withdrawing properties of carbonyl groups, significantly decrease the reactivity of adjacent amines, thereby mitigating the risk of nitrosamine formation. By evaluating APIs using these criteria, one can more accurately assess the risk of nitrosamine impurities
Also Refer: A new framework for identifying nitrosamine risks (Adare Pharma Solutions)
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