Bioequivalence and Bioavailability Forum

Dear Dan,

What I have seen or heard of several times is studies where the validation had been done with CPDA, standard/QC samples in the study were also prepared with CPDA plasma, but subject samples were taken on EDTA or heparin. Observation during the sample analysis: two-fold difference in IS response between the two anticoagulants. Investigations: difference in matrix effects, not corrected by the internal standard. Consequence: all concentrations were inaccurate.

I don't think regulators would accept the fact that the concentrations are just as inaccurate for the test as for the reference as an excuse for a lousy method... The problem is also that in my experience the difference in IS response and therefore the level of inaccuracy varies from run to run.

Regards
Ohlbe