Chromatography Forum

I'm currently fine-tuning a headspace method for, among other things, residual DMSO. In the process of doing spike recovery with different APIs, I noticed something odd:

Depending on the exact sample, the slope of my calibration curve may be reduced by up to 20%, and this is consistent across the range of 500-5000 ppm. None of the other residual solvents in my standard exhibit this behavior (well, ok, DMF does, but to a lesser degree). The linearity is not a problem. This is very repeatable.

Has anyone else encountered this?

Sure, you may be saturating the gas in your headspace with the heavier molecular weight higher boiling point solvents (like DMSO)

In other words you may be out of the linear range giving the composition of your matrix. Or it may take a longer time to reach equilibrium that is linear. The presence of the other solvents in your calibration mix can affect the response (the speed of a linear partition) of the DMSO. The API can also affect this equilibration.

Everything in a headspace vial can affect the partition equilibrium of any of the other components. Even the amount of water in an API can affect your linearity.

Document your results very carefully. You may be glad you did at a later time.

best wishes,

Rod