Bioequivalence and Bioavailability Forum

Dear Dr RCG,

It is at the same time the same and different...

- The aim of Dilution Integrity is to show whether if you have a sample with a concentration higher than the upper limit of quantification of your method (highest calibration sample), you can dilute it with blank plasma and get the correct result. To demonstrate this you will spike a QC sample at a high level of concentration, higher than your ULOQ, and analyse it after an appropriate dilution with blank plasma.

- Partial Volume is particularly important in pre-clinical studies, where for some samples the volume of plasma you get is less than what you need for your analysis. It is less important in BE trials, where usually the volume of sample is sufficient. Let's imagine that you need 100 µl of plasma in your method, but for a given sample you only have 50 µl. You have two options: either dilute your sample with blank plasma, so that you still get 100 µl to process; or just process your 50 µl, leaving all other parameters unchanged. The first case is close to dilution integrity, except that you will have to demonstrate that it works also with a sample with a low concentration; I would not recommend the second option as you may get differences in recovery or matrix effects, but if you do it you need to demonstrate that it works.

Regards
Ohlbe