Stability indicating assay

[michaelcarolus]

Hi everyone

I have an HPLC method to determine three actives. The impurities of the API have a max impurity limit of 0.1%. At this concentration of the actives (eg. 0.1mg/ml) the impurities are not detected. If I increase the concetration of the impurities to ±10% with respect to the API the impurities are detected and they co-elute with the API. Under normal conditions we would only be concerned with the impurities at the max impurity limit (in this case 0.1%). Is my method still stability indicating although the impurities are co-eluting with the API at the 10% level?

Many Thanks
Mike

[maris]

Only in case the impurities are also degradation products.At 0.1% level they will not affect.

[DR]

If your known impurities co-elute with an API, your method is not stability indicating because it lacks selectivity.

[maris]

Stability indicating assay means that no peaks interfe with the peak of analyte. The impurities are synthetic by-products and degradants. The first group isn't changed during the stability study and , in case you are to control their content ( for exanple 0.10% each) than you can adjust the concentration of the main peak in the range the those impurities are non detected even when co-eluted with the main peak. For the degradants , which supposed to growth during stability study, this doesn't work.

Bottom line: keep the synthetic impurities under the LOD level for the prescribed concentration of the main component and separate degradants. It will be stability indicating assay.

[maris]

Of course, it's always better to separate everything, but in some cases you can follow the described above.

[michaelcarolus]

Thanks for your comments/suggestions.

MC

[gtma]

If your proposed specification for that related substance (degradant) is say 0.5%, then I would agree that if that related substance does not co-elute at say 1% (since you plan to validate a wider range than 0.5%) then it is okay to say your method is stability indication provided you show that it does not co-elute in the robustness study (hope you do the robustness study with related substances at the specification level). If the related substance does co-elute with the active in the robustness study you may have to tighten your mobile phase/sample preparation and/or have a resolution solution in the method, then you can claim that it is stability indicating method.

[syx]

I found stability indicating assay in stress condition using hydrolysis with basic, acid, peroxide, light, and heat. Can we change the media (water) to a mixture of organic solvent-water or pure organic solvent for the method, especially for water insoluble- or slight soluble API?
Please give me information about any references or articles to this case.
Thanks,
SYX

[maris]

We do it routinely in our daily practice. The choice of organic solvent is very important - should be extremly stable under stress conditions,with the boiling point close to those of water, pure enough not to interfere with the peaks from the sample (I prefer pure Dioxane). I guess I can find the references for you, if it's necessary.