N-Nitroso Carbidopa

N-nitrosamines Chemistry
1

Hi everyone,

I am conducting a Risk Assessment on a product containing Carbidopa as DS. In the DP, there are present excipients considered at high-risk for the presence of nitrites (microcristalline cellulose, povidone, magnesium stearate, etc…). Considering that the chemical structure of Carbidopa contains an hydrazine group (with a secondary NH moiety), do you think the product could be at risk for the presence of the relative NSDRI?
Moreover, considering that theoretically CPCA approach cannot be applied (since the n-nitroso group of the N-Nitroso Carbidopa is not bonded to carbon atoms on both sides), which limit should be applied?

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2

In my opinion the primary NH2 group will react before than the secondary group. The final impurity may be the corresponding azide, like in these examples:
Preparation of azides from hydrazines by using dinitrogen tetroxide as nitrosonium ion source
but it is not easy predict the final degradation products at room (or higher) temperatures.

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3

You can also check out this article:
Regulatory Experiences with Root Causes & Risk Factors for Nitrosamine Impurities in Pharmaceuticals, J. Pharm. Sci., 2023
to theoretically rule out the risk of generation nitrosamine from this structure.
The molecule also contains the catechol moiety which is very reactive and protects against both oxidation ands nitrosation.

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