Is quantitation independent of solvent?

Basic questions from students; resources for projects and reports.

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Will a peak of a given magnitude (as gauged by area) be the same regardless of solvent? Trying to obviate the need for a bunch of work. Specifically:

Imagine a natural product that is sparingly soluble in a number of solvents. A Soxhlet extract is prepared using a number of solvents. The extract is allowed to equilibrate such that there is undissolved analyte after several days. Using a syringe, 1 uL of each solvent extract is run on GC.

Will the largest peak correlate with the highest solubility? Or would I have to create a cal curve based on each solvent?
Generally speaking, yes.
However, if your sample solvents are higher in organic content than your mobile phase is, and your injection volume is high enough (assuming reversed phase LC), you can mess this relationship up by inducing poor peak shapes which can skew your results. Mobile phase pH can also cause issues if it is too close to the pKa of analyte(s). Academically speaking, if your mobile phase has strong absorbance in the wavelength range in use for detection, you can limit the dynamic range of the detector (meaning you will run into sensitivity problems).
Thanks,
DR
Image
A quick answer - the solubility of the analyte should be roughly proportional to the response in the solvents. The different solvents will have variable inlet effects so that there won't be an exact correlation. The easiest way to tell is to test it.
You will have to decide how much error you can tolerate.
You also have to consider temperature program and inlet temperatures. If the solvent boils above the starting temperature you will get the solvent effect, if it boils below the starting temperature you won't. If the inlet is too cold one solvent may vaporize and another may not. It is normally good practice to make standards and samples in the same solvent when possible to negate such effects, but if looking at simple area of a peak with no calibration, it should give you an approximation of solubility but those effects will come into play. If the numbers are vastly different you should be ok with the estimation, if they are very close, then maybe not.
The past is there to guide us into the future, not to dwell in.
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