We are having an unusual problem with a cation- exchange method. The mobile phase is 20% buffer containing TEA-HCL & KH2PO4, pH lowered to 3.10 w/ H3PO4; & 80% ACN. The problem is that a small broad peak begins to elute intermitently & unexpectedly during a run. The peak will show up about every 20 minutes after an injection & then will mysteriously disappear later. I've done an investigation and determined that it is not coming from the mobile phase, std or spl. It is also not instrument specific since it will appear and disappear on different instruments. Any suggestions?

If the peak is much broader than the other peaks near the same retention time, there's a good chance that it's actually a late-eluter from a previous injection. Try equilibrating the column for a looong time (e.g., overnight), then inject a single sample that you expect might be fairly dirty and just let the chromatogram run for a while.

If you want to know where to look, calculate the retention time/width ratio for most of the peaks in your separation, then measure the width of this peak and back-calculate to get its approximate retention time.

Dealing with the problem is another matter. You may choose to live with it (if it's broad enough, the data system can deal with it), change the conditions slightly so that it doesn't coelute with anything you're interested in, change the sample workup to eliminate it prior to chromatography, or use a guard cartridge and switching valve to keep it from getting onto the analytical column.

Good luck!

-- Tom Jupille / LC Resources Inc.