Bioequivalence and Bioavailability Forum

Dear Ken,

❝ Do you mean instead of using drug solution, we should compare with sample spiked post-extraction. Kindly elaborate.

Yes. Actually you can easily combine matrix effects and recovery experiments:
- extract spiked samples in 6 different lots of matrix
- spike the same 6 lots of matrix post-extraction, at the same level of concentration
- prepare neat solutions, at the same level of concentration
- inject all these samples
- compare the response in spiked samples to samples spiked post extraction: recovery
- compare the response to samples spiked post-extraction to neat solutions: matrix factor
- if you compare the response in spiked samples to neat solution: what you see is a kind of overall efficiency, which takes into consideration recovery + matrix effects.

❝ What about samples that do not go through extraction step ? Plasma samples treated with just the addition of ACN or methanol before injecting into LCMSMS.

I agree with Nobody: part of your analyte and IS can get trapped in the precipitate and the recovery may not be 100 %. It depends on the precipitation reagent, the way it is added, how you mix the sample afterwards, etc.