What are the guidelines for choosing between an external and internal standard calibration. I am trying to develop a method for measuring the amount of inhibitor (p-methoxyphenol) in an acrylate ester monomer. I am not sure whether it is better to use an internal standard calibration or external calibration. I have a Waters 600E MSDS, a Waters 717 autosampler, and a Water 2487 variable wavelength detector.

I think, there are no official guidelines.
In praxis, the accuracy of the injectionvolumes by your 717 autosampler should be ok for an external calibration.
For an internal standard method you have to find a
substance similar to p-methoxyphenol but with an
other retention time near by p-methoxyphenol.
If you have a matrix effect itīs the better choice.

Thanks for your help. Based on your reply, it sounds like I would be better off with the external calibration provided there are no matrix effects. How do I determine whether or not there are matrix effects?

You determine it, if you find essential more or fewer p-Methoxyphenol as you spiked the sample of acrylate ester monomere!
Take care that the linearity is satisfactory!

Depends on your sources of error. If the dominant source of error is signal/noise ratio (i.e., you have relatively small peaks relative to your baseline noise), then an internal standard will make things worse. If the dominant source of error is volumetric (sample workup, injection volume, etc.), then and internal standard will help.

If you have other clearly resolved peaks, you can try a "pseudo internal standard": measure the ratio of the p-methoxyphenol peak area to the area of another peak. If the precision of the area ratios is *better* than that of the areas, then an internal standard will help.

-- Tom Jupille / LC Resources Inc.

Have you considered standard addition instead of external or internal standard. No matrix problems and the analyte itself is the standard. Injection volume problems can be overcome with a surogate standard. Rules for surogate standard selection are less stringent than for internal standard selection.