Probably involves both surface-tension effects and also minimizes ion suppression by TFA if you were using that. May not be the whole story in your specific case, but certainly contributes.

Here's the abstract from an early paper from the (then) HP analytical group:

Trifluoroacetic acid (TFA) and other volatile strong acids, used as modifiers in reverse-phase high-performance liquid chromatography, cause signal suppression for basic compounds when analyzed by electrospray ionization mass spectrometry (ESI-MS). Evidence is presented that signal suppression is caused by strong ion pairing between the TFA anion and the protonated sample cation of basic sample molecules. The ion-pairing process "masks" the protonated sample cations from the ESI-MS electric fields by rendering them "neutral. " Weakly basic molecules are not suppressed by this process. The TFA signal suppression effect is independent from the well-known spray problem that electrospray has with highly aqueous solutions that contain TFA. This previously reported spray problem is caused by the high conductivity and surface tension of aqueous TFA solutions. A practical method to enhance the signal for most basic analytes in the presence of signal-suppressing volatile strong acids has been developed. The method employs postcolumn addition of a solution of 75% propionic acid and 25% isopropanol in a ratio 1:2 to the column flow. Signal enhancement is typically 10-50 times for peptides and other small basic molecules. Thus, peptide maps that use ESI-MS for detection can be performed at lower levels, with conventional columns, without the need to use capillary chromatography or reduced mass spectral resolution to achieve satisfactory sensitivity. The method may be used with similar results for heptafluorobutyric acid and hydrochloric acid. A mechanism for TFA signal suppression and signal enhancement by the foregoing method, is proposed.

Kuhlmann, et al., JASMS,6, 1221-1225, 1995

Thank you for answering John. It sounds promising.

Best wishes.

Tom

Hi,

other substances added to your solvents might be DMSO (5%), which helps to increase the intensities, stability of electrospray and positive ID according to:

http://www.nature.com/nmeth/journal/v10/n10/full/nmeth.2610.html

or PEG, which prevent peptide losses by decreasing its adsorption:

http://pubs.acs.org/doi/abs/10.1021/pr400183v

might be worth considering.

regards

Following extraction of proteins we perform sample preparation by modification, and labeling. 2D-DiGE-Xcise and tryptic digestion follows. The tryptic digest sample is then extracted by 30- 50% ACN or IPA. In case IPA was used we centrifuge, decant the supernatant into new tube. concentrate the sample and dissolve in 30-50% ACN. Any ways, 50% IPA precipitates undigested protein, trypsin and washes TFA leaving peptide in the solution. IPA by washing away TFA may help minimize supression due to TFA and remove contaminating undigested protein noise.