Chromatography Forum

I wonder if TFA can cause problems with ESI-MS, even if you run in negative mode. I guess you will see a lot of TFA in the background, but will it also cause ion suppression? You think that it shouldn't, but I am not sure.

My analytes are mostly polyacids, which need a low pH (0.15% TFA) to be separated - but a high pH to be detected by the MS. So that will rule out the popular "TFA-fix" (propionic acid in IPA).

After some Google searches I realise that TFA will be a huge problem in negative mode also - but more due to a "competing effect" of the negative charge than ion-pairing.

Then you start to wonder... Must there not be a negative mode "TFA-fix"? Would it be possible to do post-column infusion with a positive ion that will form a strong ion-pair with TFA - and in that way make the TFA invisible for the MS? Has anyone seen this in the litterature - and what ions are likely to form a very strong ion-pair? How about a TEA... Will fix my pH at the same time.

could you try an alternative column chemistry where it doesn't matter if your acids are charged, e.g. Hilic? Then you might be able to dispense with the TFA altogether and return to MS-friendly solvents.

That is a possibility that I need to explore.

But from a scientific point of view - a good "TFA-fix" in negative mode should be something to make a good poster about. I cannot find any reference to this (important?) subject anyway.

I wouldn't go there for a couple of reasons:

1) When you add a counter ion to TFA, the resulting salt is generally non-volatile, so non-compatible with your MS.
2) Let's say that point # 1 was not an issue, something that will form a strong ion-pair with TFA might have the same result with your ionizable compounds and now you are back to the original problem...

Probably my original idea is really bad - maybe the problem will go away by itself when I increase the pH after the column? A strong base should pull protons from both TFA and my analyte. Not looking for masses below 150 anyway, the TFA should pass unnoticed. Or will there still be problems?

The higher detected mass range is not a real solution (in theory you could go this way even without a doping agent after your column) because the problem is in the instrument interface and not in the analyzer: the most ionized compound would be TFA in any case; the mass range can help you only on the graphics of your spectrum and not in the intensity.

I wonder if TFA can cause problems with ESI-MS, even if you run in negative mode. I guess you will see a lot of TFA in the background, but will it also cause ion suppression? You think that it shouldn't, but I am not sure.

My analytes are mostly polyacids, which need a low pH (0.15% TFA) to be separated - but a high pH to be detected by the MS. So that will rule out the popular "TFA-fix" (propionic acid in IPA).

Going back to fundamentals, is it absolutely crucial that TFA be the acid that helps to resolve your analytes? Will none of the more "MS-compatible" acids work well?

Let us know how it ultimately turns out!