N- nitroso Nitazoxanide

Dear Nitrosamines Experts!!!,

Hope everything is controlled and within the limits :grin:

Iā€™m wondering about the possibility of formation of N-nitroso Nitazoxanide due to formula as the manufacturing process includes acidic pH range (3.0-6.5) favored by citric acid as buffering agent.

The CPCA decision tree; attached;

The structure of N-nitroso nitazoxanide has no alpha hydrogens on its alpha carbons; so its potency will be controlled according to category 5 with AI= 1500 ng/day.

I need your support and experience to make sure about its possibility of formation and the limit of controlling it.

My regards,
CPCA scoring for N -nitroso cpds.pdf (224.7 KB)

N-nitroso Nitazoxanide

This compound is, Iā€™m afraid, a nitrosoamide, not a nitrosamine. The CPCA is therefore not applicable, since the diazonium ion can be formed by abiotic decomposition of the amide [Ponting and Foster, Srinavasan and Lambert].

In terms of determining a safe limit for this compound, therefore, I would suggest read-across to any comparable structures (e.g. aryldiazoniums formed from other nitrosamides). We are working on expanding SAR understanding to these, but there is no regulatory indication yet.