In our product NDSRI (API related nitrosamine) is present. To develop a method to quantify that Nitrosamine i dont have a standard in my hand (Not even available in the market). How can i approch such kind of method development for the quantification of Nitrosamine impurities.
How do you came to know that NDSRI is present in your Product ?
If you excipients are free from Nitrite then there is no risk for NDSRI.
can you share chemical name any how.
The short answer is you can't however there are options to do a semi-quantification with a close related analyte. You need to nitrosamine standard that is available in the market that has a similar structure to the compound that you want to quantify and use it for the calibration and quantification of your sample. In that way you are assuming that the response would be quite close since they are compounds from the same family.
Yes and No! No, since you need an 'reference standard' for both a retention and quantification match (via a linear curve).
Yes, if you are using an MS/MS and using a 'common' internal group for quantification. However, a reviewer will have a 'field' day picking holes through your method, like:
1. Other chemical entities which are not nitrosamines may give a false positive result.
2. You must demonstrate that known nitrosamines have about the same detector response (RRF).
3. ....
Andreu Fabregat Rossell thanks for the Answer,
In that case, can i use my API (Which have the same Structure) as a standard ?
Tabrez Shaikh Thanks for the suggetion,
We have identified the mass of Nitroso impurity using LCMSMS.
Bruce Neagle Thanks for the comment, As i said, can i use my API as the Standard, because both have more or less same physical and chemical properties.
Yes. We do this for unknown impurities since we do not have internal standards (we use the API's Relative Response Factor or RRF). Your best bet is to use a core 'common' to all Nitrosamines (just like Heme in Hemoglobin).
Further to my comments. This method (and all its warts) will be reviewed by the FDA (Center for Drug Evaluation and Research OR/AND Food Safety Investigation Service) or country equivalent. Thus, it might be better to eliminate Nitrites and Nitration Agents (like Nitric Acid) from your manufacturing process. If you cannot then perform a 'Forced degradation' study of acid, base, heat, light, oxidation, however be sure to use Nitric Acid as your acid on the API (0.05 N for 5 days). Develop a potential degradation pathway.
Have you read the JOC paper Article An Organic Chemist’s Guide to N -Nitrosamines: Their Structu...
? There are nitrosamines reference materials available from USP and both Agilent, Waters, and ThermoFisher have technical notes available to help you develop a testing method. In the JOC paper is covers routes of formation and testing methods.- Badges
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