Bioequivalence and Bioavailability Forum

Hi John,

Thanks for the update.

❝ There is no stated requirement for a full validation, however it is not sufficient to demonstrate lack of interference. The stability of the quantitated analytes must also be re-evaluated.

If we have to re-evaluate the stability (QCL and QCH), then I wonder why do we have to demonstrate lack of interference.
Well, I agree that conc. between LLOQ and QCL wouldn't be covered by stability experiments. But in reality, how much do these low concentrations really influence the outcome of BE study.

Which stabilities should be re-evaluated for a co-dosed compounds? Only F/T and longterm as proposed in the FDA letter? How about benchtop stability in matrix and stability of extracts?

To go even further....why would possible co-medications such as paracetamol be treated differently.

And last but not least....the real "problem", which is IMHO the most important in such cases...the metabolites (glucuronides, lactones, N-oxides,...) which can convert to parent drug and are present in significant (what is significant level ) concentrations compared to the parent drug.
How should they be evaluated (not to mention, how hard it is to obtain these standards in sufficient purity to begin with)?

And then I hear from people outside my lab that bioanalysis is easy .
The world of bioanalysis gets more and more comlicated each day.

How do you see this situation?

Cheers
Marko