Chromatography Forum

Can anybody help me?
I search tablets sample preparation technology, because my recoveries are only 95 %. I solve my tabletts in pH=2 buffer, are sonicated 10 min, but the active gradients are binded up to placebo.

I do not know what the nature of your actives and the placebo is. Here are a few different suggestions to think about:

if you suspect that the interaction is through hydrophobic binding, add a bit of methanol.

if you suspect that the issue is caused by ionic binding, change the type of acid or the pH.

I have tried change pH (2-8) and methanol V/V% of my dissolver, solvent heating (37°C), dissolver volume enlargment but these don't cause more recovery.

How accurate, or at least how precise, is your analyticl step?

If I put the active gradients upon the placebo then the recovery will be about 100%. Sample preparation's precision: RSD = 0,5-1 %. Low recovery are only form tabletts.

My suspicion is (especially since the loss is quite small) that you have a procedural error which is responsible. Maybe your method would require 100% recovery of the extracting liquid but you are loosing a little with (in) the ground tablet material? Placing extractant ON the placebo means you recover all the liquid here?
Also, it is possible that with 1% RSD your method is not sensitive enough to detect a diff. in recovery due to the pH and/or MeOH change.

Hmm...
How about if the pills are too low to start, and your preparation is correct?

The fact is that the content uniformity values have RSD = 3-4 %, this may cause that I didn't detect difference in recovery due to the pH and/or MeOH change. In the assay measuring I homogenize 10 pieces tabletts.

When I examine the recovery I put active gradient's standard powder upon the placebo tabletts and I do the steps of sample preparation technology.