Chromatography Forum

Hi All

I have an impurity method that uses Area % (normalization) as a means of calculating the impurities. I would like to know how one would validate a method for this type of calculation?

Traditionally we, have used external std method for all our impurity methods. This is the first one that we need to validate that uses Area %, and hence we have limited experience.

My initial thought process was to validate the method as an external std method and then compare the results to the Area % calculation. If the two methods show equivalence, then we can use Area % in the future.


Any help/suggestions will be greatly appreciated.

Regards
Mike

Hello.

Usually you have to prove a linearity for main compound from 80 % of disregard limit up to 120 % of nominal concentration. Other is similar with external standard method validation.

Regards
Dmitriy

% Peak Area is not acceptable as you may have a different response factor than your API (due to a different chemistry and structure). You MUST manufacture the impurity or have it made by an outside laboratory (organic chemists). Then as part of linearity per ICH Q2 you MUST demonstrate a curve of concentration (mass) versus detector response.

% Peak Area is not acceptable as you may have a different response factor than your API (due to a different chemistry and structure). You MUST manufacture the impurity or have it made by an outside laboratory (organic chemists). Then as part of linearity per ICH Q2 you MUST demonstrate a curve of concentration (mass) versus detector response.

Same claims if main compound is a single external standard…

Hi

Thanks for all the suggestions. I will determine RRF's and then establish if Area % determination is suitable.

Thanks again.

Mike