Chromatography Forum

I have a mobile phase with Sodium 1-heptanesulfonate and Potassium dihydrogen phosphate acting like ion-paring for my component. However I need to identify one impurity by LC-MS. Once this mobile phase is incompatible with LC-MS which mobile phase should I use?

Don't know if there is any.

But if the compound needs Ionpairing maybe HILIC with MS could be woth a try.

I was wondering if hexafluoroisopropanol with triethylamine could do the job of ms compatible ion-pairing additive for cationic compounds. This combination is being used for LCMS of oligonucleotides, but I have not heard about it being used for basic analytes.

The whole point of ion-pairing is that the IP additive is opposite in charge to the analyte. If your original phosphate buffer was at low pH (<3), then heptafluorobutyric acid might be a reasonable choice. If the original buffer was at higher pH (6-8), you might have to adjust the pH up with something like triethylamine.

polyfluorinated ion pair reagents can be really, really hard to get out of an MS system. If you run your LC-MS with heptafluorobutyric acid, expect to see heptafluorobutyrate ions in negative mode for the rest of your career. If you only need to identify one or two impurity peaks, is it possible to collect them and re-inject on an LC-MS system separately so you don't need to set up a full ion-pair method on the LC-MS? Always nicer to inject a small amount of something troublesome in the sample rather than use it in the running buffer...

Personally, I would stay WELL away from an ion-pairing agents rather than contaminating the LC/MS system. Typically, a more non-polar column (higher %C) can mimic the chromatogram. You may need more method development and validation.