Bioequivalence and Bioavailability Forum

Dear Dr RCG,

❝ 1. In DI processing volume is constant. e.g if processing volume is 500µl, then you will add 500µl to the sample - mix well and process only 500µl of it.

Not necessarily. You can also directly take 250 µl + 250 µl into your extraction tube.

❝ since DI and PV has different way of sample preparation.

❝ so my point of view is that we should do different set of experiments for DI and PV

Sample preparation may not be different. However the level of concentration can be different: dilution integrity will be done at a high level of concentration (higher than the ULOQ), but it would be better to do partial volume at a lower level of concentration (so that after dilution you get a concentration close to the LLOQ, or within a few times of the LLOQ. This will better reflect what happens in your study.

❝ and also mention in the method validation SOP.

Yes. But depending on the type of samples you get to analyse, you may not need to do partial validation systematically. If you have to analyse samples from pre-clinical studies or from clinical studies in children, then it would certainly be a good idea to do it as you are likely to get some samples with insufficient volume. If you analyse samples from PK studies in human healthy subjects, unless you have to start from 1 ml of plasma it is usually not needed.

Regards
Ohlbe