Bioequivalence and Bioavailability Forum

Dear Marko,

❝ However (as every analyst except regulators knows ), from time to time it is not so easy to integrate all chromatograms within the batch consistently with one generic method.

Agreed, particularly with low concentrations and noisy baselines (which you will get without smoothing).

❝ we (...) never apply smoothing (again historic regulatory tabu).

I have never heard of regulatory authorities objecting to the use of smoothing. Are you thinking of any specific agency ?

I agree with Helmut: it can be challenging or even impossible to integrate chromatograms properly without some level of smoothing. Though I agree that smoothing should remain reasonable (the idea is not to mask chromatographic problems and shoulders which could be due to interferences !), it is needed.

One question could be whether to authorise changes in smoothing within a study, if one run is noisier than another. Within a run I would consider that the smoothing should remain the same for all samples (it will affect peak area and therefore the concentration). Between runs I would probably try all other parameters first...

Regards
Ohlbe