When it comes to different types of GC techniques, headspace (HS) analysis is about as clean as they come. Typically, hundreds of injections can be made without doing any inlet maintenance or column trimming. It is one of my favorite techniques in the lab since it encompasses countless different unique applications. Even though HS is the coolest thing since sliced bread, it can be tricky at times. I recently found this out while working on a collaboration with a researcher at a university. The research is focused on immunometabolism, which I know nothing about, but this researcher needed help testing some mouse feed containing an additive for residual solvents, which I know something about! So, I set out on my task to test their mouse feed for residual solvents, and encountered something that could help other scientists out there doing HS -- the importance of running matrix matched calibrations.
Sometimes it is assumed a solvent based calibrations will apply well for samples via HS because in theory all of the volatile analytes are driven into the gas phase. To disprove this, we ran a quick test comparing analyte responses at the same concentration; one vial with standard only and the other vial that is matrix matched.
Comparing the responses for these compounds, methanol in the solvent based vial was ~7x higher than the matrix matched vial and acetone in the solvent based vial was ~3x higher than the matrix matched vial. If we were to calibrate off of a solvent based calibration, we have the potential of reporting a false-negative for the presence of methanol and acetone in the additive. It was decided that we matrix match the calibration standards in order to give a more representative response.
Moral of the story when analyzing samples by HS: no matter what type of analysis is being conducted, it is extremely important to run calibration standards as similar as possible to the sample matrix that is being analyzed to ensure that you are producing accurate and reliable results!