I am trying to develop an acetonitrile gradient method with an eluent buffered at a pH of 2.5 for LC-MS (electrospray ionization source). I am trying to avoid TFA because it supresses ionization (and consequently signal) due to ion pairing. Does anyone have an electrospray compatible buffer for pH 2.5? Also, does anyone have experience with ion-pairing reagents with gradients and electrospray LC-MS (for example, is tetrabutylammonium bromide compatible / volatile)? Is there any good reference available that lists electrospray compatible / volatile reagents? What is the critical temperature for volatilization (e.g. electrospray chamber temperature or capillary/quad temperatures)?

I am going to have the same problem.
I have an HPLC method with ion pairing at 2.5 (Heptasnosulfonic Acid) and I would like to use an MS to identify uknown compounds. I would like to try using TFA NH4 to adjust the pH at 3.0 or 2.5 but I do not know if I woul have problems with supress ionization.

Do you have any idea ?

If you just need an acidic mobil phase, use formic acid. You can use TFA if you need the ion pairing, and yes ionization will be supressed. The supression can be overcome by using the "TFA FIX" which involves adding propionic acid post-column to the solvent stream.

Tge formic acid works fine in the electrospray mode.

Hi,
in general you should take care using buffers containing non-volatile ion-pairing agents like tetrabutylammonium bromide. A suitable alternative is the use of equimolar amounts of a trialkylamine (e.g. tributylamine) and acetic acid.
The loss in sensitivity caused by the presence of the ion-pairing agent can be avoided by using a (self-generating) cation suppressor inserted between the LC column and the MS interface. Works fine and you also get rid of disturbing alkali ions.

If you want to buffer your solution, try
ammonium formate/formic acid. Unbuffered,
formic acid can be used. For higher pH try
using ammonium acetate/acetic acid

The ammonium formate or acetate are your best bets. The ammonium trifluoroacetate doesn't work because the salt doesn't dissociate which translates to excessive noise in the baseline.

But, which is the maximum amount of ammonium formate or acetate that I can use to simulate an ion pairing without having problems with the HPLC system ?

Is it possible for the HPLC Colum or MS system to work with a 100mM buffer?.

F.M: 25 % aquous/ 75 % Organic (ACN)

Thanks again !!

Kaf,Unfortunately with only ammonium acetate (and 75% ACN!) you won’t be able to simulate ion-paring effects.
Now, about volatile ion-pairing reagents compatible with MS:
Anionic ion-paring reagents: All ion-pairing reagents type alkylsulfonates are not volatile and should be replaced by long perfluorinated carboxylic acids (TFA or higher homologues). You can increase your side chain until pentadecaflurooctanoic acid and still be volatile. However, you can not buffer these reagents with a base as non-volatile salts are formed. For volatility of these reagents, equilibration times with C18 and porous graphitic carbon (PGC) supports, compatibility with MS and retention of polar compounds you can see in:
K. Petritis and co-workers
J. Chromatogr. A 833 (1999) 147-155.
J. Chromatogr. A 855 (1999) 191-202.
J. Chromatogr. A 870 (2000) 245-254.
J. Chromatogr. A 896 (2000) 253-263.
J. Chromatogr. A 896 (2000) 335-341.
For the “TFA-fix” mentioned above the original paper is: F.E. Kuhlmann, A.Apffel, S.M. Fischer, G. Goldberg, P. C. Goodley, J. Am. Soc. Mass Spectrom. (1995), 6, 1221-1225.
Cationic ion-pairing reagents: All ion-pairing reagents type tetrabutylammonium are not volatile and should be replaced by n-alkylamines. Fortunately, until heptylamine you may buffer with volatile acids (formic, acetic etc). For more details you’ll have to wait some forthcoming papers.

I am trying to analyse C3-C7 carboxylic acids (mono and di and also with OH) with LCMS. We bring sample to pH 2. Using ESI+ and MeOH/H2O(90% to 30%)+ HCOOH we got lots of cluster ions and almost no M+H?? With TFA NO linear C1-C6 can be seen and ONLY the diacids give nice M+H ???
Should we stay with formic acid and perhaps APCI??