Chromatography Forum

We run a HPLC Dissolution method that can show large variations in the solvent front we get on the chromatography. We have narrowed it down to the Sodium Hydroxide but it will differ even if the same brand of the reagent is used. Has anyone had this problem before? From a regulatory point of view will it be a problem if the chromatograms have different solvent fronts on the chromatography between batches but the peaks of interest are OK?

Thanks in advance

"t0 noise" from unretained junk is common and as you have experienced, can be quite variable.

From a regulatory point of view will it be a problem if the chromatograms have different solvent fronts on the chromatography between batches but the peaks of interest are OK?

Does your method include anything about t0 in the system suitability criteria? So long as you meet system suitability, your system is suitable.

Thanks Tom, is it not strenge that every thing is the same but the chromatogram looks different?

I wouldn't be concerned over things that are of no concern.

That sounds like the master chromatographist Yogi Berra said that, but there's enough real world stuff to worry about.

Not really. You start off with a chromatographic system at steady-state (i.e., close to equilibrium) and then you disturb the equilibrium by making an injection. Until the system returns to equilibrium, it's in a chaotic state, with everything that implies about (non)repeatability and (non)predictability. That's why the FDA Guidance suggests that quantitation should be done on peaks with k'> 2; that ensures that they are outside that chaotic region.