Recovery Issue with GC-HS residue solvent study

[nathanlin]

Hi there,

I am working on a liposome product. However, I have an issue about the residue solvent recover study.

I am currently using IPA as IS for MeOH detection. However, with current conc., my recovery is around 50%. If using 5 times higher conc., the recovery can go up to 80%. If using 5 times higher conc. and one half of my product, the recovery would be around 100%. I am thinking it is the problem of matrix effect, but not sure how to solve the problem. Since I need to meet the ICH guideline, current Conc. and the amount of sample is at the limit already. change the shaking frequency and increase the oven temperature?

My sample preparation is listed below:

STD: 1mL STD W. Solution (600 ppm MeOH in Diluent) + 9mL Diluent (w IS)
Sample Ctrl: 200 mg sample powder + 10 mL Diluent
100% Sample Rec.: 200 mg sample powder + 9 mL Diluent + 1mL STD W. Solution (600 ppm MeOH in Diluent)

Any suggestion would be appreciated.

Thanks!

[Peter Apps]

Welcome to the forum.

Does your sample dissolve in the diluent, or are you making a suspension ?

Just to be sure; how are you calculating recovery ?

Peter

[nathanlin]

Thanks for the reply. Since the sample has salt, lipids, etc., the final solution is not transparent. It is more like a suspension.

The recovery is comparing the 100% spike solution response factor to the STD solution response factor. The response factor is the area of MeOH divided by the IPA (IS) peak area.

[Peter Apps]

It certainly looks as if there is a strong matrix effect, and quite possibly it is non-linear.

You could try saturating your diluent with salt, using ethanol as the IS, or calibrating by known additions which does not need an IS.

Peter

[mckrause]

Can you give us some of the missing information? What is your HS temperature? Are you over pressuring prior to filling your loop? If so, to what pressure?

Normally when you see this type of effect in HS it means exactly what Peter said, which is that you need to use known addition. Typically this would indicate that you are experiencing problems based on the fact that you have solids present. However, it also could be that your temperature is too low. I would also recommend, since you are dealing with alcohols, that you saturate with salt. I don't know if your diluent already has salt, but if you are not working in near-saturation levels with alcohols you will run into this type of non-linearity that appears to be matrix related (in fact, is matrix related).