Chromatography Forum

Hi all,
It has been quite long since my last post!!. I have a question,
In our drug product related substance chromatogram there are some peaks observed sample as well as in placebo. However, the peak response is higher in the sample (40 to 50% higher). Should we have to report it? Anybody faced such issues?. How to go ahead about that?

Appreciate valid responses,

Thanks
Vijayak

Yes, I have seen this several times when running related substances samples for stability conditions such as 12 months at 40 degrees etc. Yes, if the sample peak response peak is 40-50% higher, I would definitely say you need to report it, there isn't really a justification to dismiss it as a placebo peak if they are that different. Question: are you comparing similar samples, is the sample at 12 months accelerated temperature and the placebo at room temperature?

It almost sounds like you have a new RS eluting at the same retention time as your placebo peak (this new RS could be coming from the placebo and not the API). Do you use an MS detector (which can identify this peak, maybe)? Have you performed 'forced degradation' on the API?

Yes, I have seen this several times when running related substances samples for stability conditions such as 12 months at 40 degrees etc. Yes, if the sample peak response peak is 40-50% higher, I would definitely say you need to report it, there isn't really a justification to dismiss it as a placebo peak if they are that different. Question: are you comparing similar samples, is the sample at 12 months accelerated temperature and the placebo at room temperature?

Question: are you comparing similar samples, is the sample at 12 months accelerated temperature and the placebo at room temperature?[/quote]

Thanks EmpowersBan. Yes we are observing this in ACC 6 M and 12 M samples and also we are comparing against corresponding placebo exposed in the sample condition.

Its possible there may be some secondary or tertiary degradation occurring when the placebo is in the presence of the active at these conditions, compared to just running placebo on its own. If you use a PDA detector you could compare the UV spectra of the placebo vs the placebo in sample, maybe manipulate the view to derive the second derivative of the spectrum and see is there any co-elution or shouldering going on with spectra similar to your active.