Impact of Different API Salts

[MarkS]

Has anyone had any experience of the impact of different salts of the API on nitrosamine formation?

I’m sure I read somewhere around any HCl salts being particularly bad for nitrosamine formation, but I have read so much now that I can’t find it any more.

[Naiffer_Host]

I have not read any research on this? @schlinjo1975 @AndyT do you know of any?

[MarkS]

I hope that nitrosamines haven’t taken over my life so much that I dreamt it!

But if I did dream it, and it works, then you read about it first here.

Obviously not a solution for all APIs with the changes that would be necessary both from a formulation and registration perspective, but a potential for some.

[mflorea]

HCl is a proton source and Cl- catalyses the nitrosation by forming NOCl species.
This is one of the references mentioning the higher reactivity regarding nitrosation of API HCl salts than free base:

and also

[Naiffer_Host]

N-Nitrosamine Formation in Pharmaceutical Solid Drug Products: Experimental Observations -Pub

Publication " N-Nitrosamine Formation in Pharmaceutical Solid Drug Products: Experimental Observations" by Moser et al. Link: https://www.jpharmsci.org/article/S0022-3549(23)00028-X/fulltext Abstract: The potential presence of N -nitrosamines in medicinal products has become a matter of concern for health authorities and pharmaceutical companies. However, very little information is available in published literature on N -nitrosamine formation within pharmaceutical drug products. In response,…