Straight dope on using trifluoroacetic acid (TFA) with MS?

[Arne]

Hi All,

I have had a customer requerst of running one of their HPLC methods on LC-MS. They are using 0.25mL/L (3mM, 0.03%) TFA in their mobile phase.

I have heard tales of suppressed negative ion-mode even long after removing the mobiel phase from the system.

What is the stright dope on the consequences of using TFA on LC-MS systems?

Will 0.03% TFA in the MPh make analysis in negative mode impossible? What about strong acid analytes, such as sulfonic acids - will they still give signal in the presence of TFA?

Thanks as always!

Arne

[Multidimensional]

Quick answer: While 0.03% is a low TFA percentage (a good choice), use of TFA will indeed contaminate the entire flow path of the system. This includes the plastic lines used, the column, any vacuum degasser and the MS source. Unless you can dedicate the instrument to the one application, the basic guideline is, do not use ion pairing reagents with LC-MS systems. Yes, it will greatly suppress negative signals AND add extra ion peaks in both modes, plus many adducts. It may take several months and lots of $$$$ money to remove the contamination afterwards.

More info can be found at this link: https://www.researchgate.net/post/Which_ion_pair_reagents_are_compatible_with_LC-MS

[JMB]

As an additional observation, the TFA anion forms a very strong ion-pair with positive ions, thereby reducing the signal in the +ve ion mode.

A better choice is to use formic acid.

[lmh]

I've not had any problems getting rid of it (though I suspect this is instrument-dependent, and the degree to which it's important to get rid of it will depend on the applications you're running, too), but I agree completely with the last person to post: it will give totally rubbish ionization. I find that it takes a while for it to build up to a level where ionization fails. Typically, a user decides I'm talking nonsense when I suggest replacing TFA with 0.1% formic acid, runs a standard, and it looks fine, so they express enormous smugness that they're right and I'm wrong. Then they run all their samples, and they see a bit of something in the first run, trailing off to nothing in the later runs, and they come back the next day telling me that the instrument has lost sensitivity. I try to keep calm and polite, and again suggest replacement of TFA by formic acid. They think I'm just trying to score points and go off dissatisfied. What can one do?
TFA is amazingly good for chromatography, and amazingly bad for mass spec. It's been a long time since I tried the TFA fix, post-column addition of something else, but when I last tried it, it made things worse, not better. I am not a fan of TFA!

[James_Ball]

Also, if Formic isn't strong enough you can use Acetic Acid. One of the current EPA Drinking water methods for Anatoxin uses it and it works great for us.