Why is best to run acids in negative mode in LC/MS/MS ?

[saioa]

Hello,
I understand that it could be best to use a negative mode as it is easy to ionize acidic pharmaceuticals. However in LC they should be neutral so they can be separated and that is usually done by having an acidic mobile phase, which I could think it would decrease the signal in the MS.
What would be best mobile phase option in this case?
Thanks

[Noser222]

My take on it is that there is always some ionization of your analyte in an acidic mobile phase, and "some" is enough to be detected. If you get too acidic, like if you have TFA in there, then you start killing your signal.

[Mark Tracy]

You can also use post-column addition of ammonium hydroxide.

[H-KP]

Hello,
You should test the two modes using a neutral mobile phase.
If ammonium acetate is added in the mobile phase, you can monitore in the positive mode on the +NH4 adduct.

[Uwe Neue]

A buffer instead of a straight acid additive might help as well. Instead of using formic acid, use an ammonium formate buffer at pH 3.75.

[james little]

You might find this article useful..

"A Study of Ion Suppression Effects in Electrospray Ionization from Mobile Phase Additives and Solid-Phase Extracts," Claude R. Mallet, Ziling Lu, and Jeff R. Mazzeo, Rapid Communications in Mass Spectrometry, 2004; 18: 49-58

[saioa]

Thank you for the answers, the article has a lot good information, Thanks.
Saioa

[Magda]

If someone should use TFA what's the best concentration for him to avoid ion supression?