If NDSRIs are not detected at end of stability, is small-molecule nitrosamine testing still required?

Confirmatory Testing & Analytical Challenges
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If NDSRIs are not detected in the drug product at end of stability, is small-molecule nitrosamine testing still required?

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Hi Sannadatha

In mi opinion, the existence of a small-molecule nitrosamine is not related directly with the presence of a NDSRI.

It depends on the structure of your API. specifically, if it’s able to generate the precursor of a small-molecule nitrosamine whether by degradation pathways in long-term stability studies or during the synthesis of this pharmaceutical active.

Despite you haven’t found NDSRI’s, it doesn’t mean there hasn’t small-molecule nitrosamines even more when you identify the presence of its precursors.

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Dear Srinivas,

i think that with the term ‘‘smail-molecule’’ nitrosamines, you mean the usual NDMA, NDEA, NMBA etc.

Those nitrosamines are not related to the NDSRIs which are generally structurally relative with the API of the product.

The ‘‘small nitrosamines’’ are usually connected with the synthesis of the API and the carry over of secondary, tertiary amines and amides which are used as a solvents and/or reagents (like DMA, Et3N, DMF etc).

Anyway, the answer in your question should be come from your risk assessment, as in this document you should have check the possibility of presence of those ‘‘small amines’’ in your API which will be used for the formulation. In some cases, the API could degrade to small amines during stability and this is also a information which should be export from your risk assessment report.

thank you,

Christos

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Similar topic here:

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thanks for answering my question.

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thanks for answering my question