Currently, I am running a normal phase HPLC method using an amino column and am seeking some input on solvent composition, I'm trying to find alternatives to using the THF triethylamine combination I am right now, preferably solvents that are MS friendly. Any suggestions?

Is there a reason that reverse phase can't be used? What ionization mode is expected, or what are the polar functional groups on your compound? More information would be helpful.

Not sure what the TEA function is in your method but methylamine and dimethylamine are similar basicity to TEA but much more volatile (especially methylamine).

Thank you for your responses thus far. A bit more information. I am using the method to examine carbohydrates, reverse phase is not good for this work; the specificity of the normal phase column is such that I can get valuable information even without the use of MS and I also do not have to permethylate the carbohydrates. I am running in ESI- mode; negative ions are good for this application due to the structural nature of the carbohydrates. I will probably try using methylamine as suggested but would also like some suggestions on an alternative to THF. Does anyone have any experience with the rugggedness of amino columns and stability of the phase to solvents in general?

I have used TEA with ACN / water mobile phases and APCI(-) ionization and it worked reasonably well. I can't remember if have used it with ESI(-) or what the result was. If it turns out that ESI(-) is suppressed by the TEA (or methylamine), I would suggest trying APCI(-) if you have the hardware. Positive ion would not be a viable option with these additives.

I once attempted to electrospray a sample (infusion) that was dissolved in THF. I found that I got very little electrospray current and hence very little signal. However, addition of isopropanol helped; can't remember how much, you'll have to experiment. A little water might work better, but I couldn't use it in my case. If a polar additive messes up your chromatography, you could add it post-column with a mixing-tee. Are you making (M-H)- ions of your carbohydrates? If so, addition of ammonium hydroxide post-column along with your polar solvent would also be helpful. If you're making adducts (e.g. with acetate or formate) to get ions, you'll want to add these salts to your mobile phase.

Never tried APCI with THF. Again, adding a protic solvent may help if you don't get good results at first. E.g. APCI doesn't work as well with 100% ACN as with 100% methanol.