I would like to start a discussion on alternative modes of chromatography to reversed phase as the front end separation to detection via electrospray mass spectrometry. Specifically, I would like to begin with people's success with ion exchange as a separation technique with good signal from the mass detector (theory, columns, mobile phases). I, for example, have had some success using polymeric strong anion exchange columns and 0.1M triethylammonium bicarbonate (TEAB) to 1M TEAB gradients in the separation of dye labelled nucleoside triphosphates. Signal is pathetic however in negative ion mode.

I interface standard suppressed ion chromatography methods to electrospray MS routinely. Typical analytes are organic acids, amines, inorganic anions including perchlorate. There is literature describing signal suppression in ESI-MS. This occurs when another ion co-elutes into the ESI-MS along with the analyte, carrying a portion of the current and thus reducing the analyte signal. Thus use of an eluent suppressor is good. The presence of solvent also helps in the creation of a "good" spray. What analytes are you working on, matrix, etc.,? I may be able to suggest some starting conditions.

Thanks for the response. Could you explain eluant suppressor a bit more please. I would like to be able to analyse organic anions such as nucleoside triphosphates by anion exchange LC-MS. I know it is possible by reversed phase but I want the selectivity option of an ion exchanger and then into an electrospray source.

A really viable alternative to RP is to use HILIC. In this mode, the mobile phase contains typically a large amount of organic solvent with some water. Much higher response factors have been reported in this mode compared to normal reversed phase. I would think that this technique generally results with much higher sensitivities than using your ion exchange method. On the other hand, if sensitivity is not important, whatever works, works.

It is possible to use the self-regenerating suppressors to remove nonvolatile buffer ions post-column. The one I used was from Dionex, and I'm not sure if other manufacturers sell a similar device. For example, if your buffer salt is ammonium phosphate, the "cation" version of the suppressor, which removes anions, will remove the phosphate and replace it with something else. This worked using DI water as the source of replacement ions, as per manufacturer instructions, but I ran into two problems analyzing organic compounds with this technique. The first problem was that phosphate was being replaced by hydroxide, the pH of the eluent increased, and I lost sensitivity as a result (this was positive ESI). One solution to this problem was to use ammonium acetate instead of DI water as the regenerant solution. The second problem was that some organic compounds interacted with the suppressor, resulting in poor peak shape for those compounds. Other compounds did not seem to be affected. I should stress that I was not using the suppressor for its intended purpose (which is really ion chromatography), and was using it with organic solvent concentrations in excess of manufacturer recommendations.

With reverse phase, it is easier (in my opinion) to avoid nonvolatile buffers and problematic ion pair reagents, and just live with the limitation, but I don't have much experience with ion exchange. If a compound requires ion pair reagents to work on a reverse phase column, or if it works well with ion exchange, it may be worth the effort to try HILIC as an alternative.

what is the difference between ion chromatography &ion pair chromatography

Ion chromatography is basically ion exchange chromatography, generally practiced with a suppressor device which removes the eluent prior to the detector without removing the analyte. In ion pair chromatography, a surfactant ion with the affinity for a hydrophobic stationery phase is added to the mobile phase. Although this isn't 100% accurate, one can think of this mode of operation as producing a "virtual" ion exchange phase. In the context of LC-MS, the suppressor effluent is highly compatible with MS whereas most common ion pair reagents are not.