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

[MG]

In my experience, you are correct that the addition of acid reduces negative ESI signal, as it tends to keep the acid protonated. But realize that in order to produce charged droplets, redox reactions must be taking place at the ESI electrode, and droplet pH will not be the same as the pH you measured in your mobile phase bottle. With a few analytes where I have investigated different modifiers, I have found that acetic acid will give greater signal versus the same amount of formic acid. And lower amounts of acid will also give greater signal versus higher amounts of acid. I usually use 0.1% acetic acid as a starting mobile phase modifier for acidic compounds in ESI(-), unless there is a chromatographic reason not to do this.

[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