Bioequivalence and Bioavailability Forum

Dear Auditor,

I can think of several possible consequences:
- some level of protein precipitation (after all, acetonitrile is the most often used solvent for protein precipitation !). You may get problems of column clogging if using solid-phase extraction.
- dilution of your plasma sample, which may result in differences in matrix effects (you will dilute phospholipids and other components responsible for matrix effects).
- different recovery during sample extraction.
- no idea whether it could have an influence on long-term or freeze-thaw stability.

One suggestion, if yo have no other choice than to use more than 5 % spiking solution due for instance to limitations in solubility: add the same proportion of acetonitrile to the subject samples during sample processing. It will at least compensate for the dilution and matrix effects problems. Not sure you will avoid problems of protein precipitation due to the combined effects of acetonitrile and sample freezing.

Regards
Ohlbe