Mass Balance

[Sunjay]

Dear All,

My question is related to mass balance.

We are doing stability of a product in which assay has degraded to 70%. For the impurities we are injecting the sample in higher concentration, using the same assay method. But the impurities are coming around 3%.

So a regulator asked us for the mass balance. As the impurities + assay account for 73% only. But should be our justification and action taken in this case?

Please help with your valuable suggestion…..

Regards

[danko]

It wouldn’t surprise me if some of the degradation products elute at the beginning of the run (void volume). Try to compare the front signal of a fresh sample to the front signal of a degraded one.

Another possibility is change of the absorption maximum for some of the degradation products.

Best Regards

[AdrianF]

You have a lot more work to do!
What is happening when it is less degraded ie 95,90,80% active. You may need different analytical techniques - at the very least diffeerent HPLC conditions to investigate. Also investigation of the chemistry of the compound to discover the most likely breakdown products. The manufacturer of the compound shound be able to help you.

[Mattias]

One suggestion would be to do a stress study where you degrade the substance to about 70% purity with acid, base, H2O2 etc.. Then you need to find methods that can give you decent mass balance independant of degradation route.

We had a situation not long ago where we had excellent mass balance for all stress conditions except high pH. I reason turned out to be that the molecule formed oligomers at high pH, and those molecules needed much more acetonitrile to be eluted. Just a suggestion, I have no clue what your molecule is like