Are there some restrictions and/or recommendations on the use of pairing agents in LC-MS. I'm analysing basic compounds. The separation is obained only at higher pH and even though, the peaks are broad.

Recommendations. Only use volatile additives. For analyzing basic compounds, presumably in positive mode, don't use basic or cationic additives like triethylamine, tetrabutylammonium, etc. even if they are volatile. You can use TFA, but use the smallest amount that improves your separation, and be aware it may cause some ion suppression. Whichever column you use with TFA, you should probably reserve for use only with TFA methods. I try to avoid using it, but I have had TFA (0.01 to 0.1 % v/v) work wonders for polar basic compounds.

Instead of ion pairing agents you should consider HILIC mode of separation. In particular for LC-MS. HILIC is suitable for polar and hydrophilic compounds.

Typically, in HILIC an eluent containing ca 70% acetonitrile and a volatile buffer like formiate or ammonium acetate are used.

JMK, if you provide me with your email address I can send you material on retention of polar compounds (amines, aminoacids, amidines, etc.) without ion-pairing reagent using LC/MS compatible conditions. You can send your inquire to mail@allsep.com

I thank u all for ur comments. By the way, what does "HILIC mode of separation" stand for?

It means hydrophilic interaction chromatography.
As with normal phase chromatography in hilic mode the unpolar compounds eluates first and water is the strong eluent.
You can use either pure silica columns or special modified hilic phases. When using Si phases take a look at the pH value for the phase. At least in NP chromatography this has influence of peak shape and I guess with hilic thats the same.

MG,
the statements of TFA adhering somewhere, or whatever, seem to get more frequent. Do you have some evidence, explanation, or refs on this phenomenon? I am still trying to figure out why my Toso Super SW 3000 (SEC column) changed permanently after contacting perfluorocarboxylic acids (including TFA).

Hans

TFA is the strongest ion pair reagent I know. It shows great interaction with the silanol surface (up to some kind of adhering).
A column which was treated with TFA shows on a lc/ms the TFA signal for some time.
When running TFA with a water/acn gradient the baseline increases strongly, and someone at the forum pointed out that TFA is diluted from the column with increasing concentration of organic solvent, which makes sense to me.
After using TFA the column has to be washed quiet well with ACN (or other organic) to flush TFA from the column. If the column is stored without washing TFA alters the column surface (or the functional groups or both?) beyond regeneration.
TFA is retained on fluorinated phases and I think it is possible that TFA complexes (especially with basic molecules) interacts with the TFA on the silica surface. (When analysing basic compounds on a fluorinated phase with TFA containing mobile phase the basic compounds RT is higher than with any other acidic RP system - expect ion pairing systems.)

Hans, I don't have references on TFA adhering to columns or LC systems, but I have experienced it. The problem isn't so bad for pumps and tubing. They can be flushed until the background returns to a reasonable level and does not cause problems. Columns are worse, and this isn't surprising as they are designed to retain things. :-) Actually, I've found that a column can be flushed of TFA enough so that ion suppression is not a big problem when doing SIM or MRM, but when going from no TFA ---> TFA ---> no TFA on a given column, the separation does not behave in quite the same way as it did before TFA was used. Also, the 113 ion will predominate the background in negative scan experiments. In my experience, the worst culprits are the small basic compounds (e.g. TEA) used in some methods. I have been supplied LC methods along with a column, where the client wanted MS on specific peaks observed in UV. Even though the method was MS-friendly, the column would be completely unusable (in positive mode) even after flushing, because it had once been used with one of these reagents.

Any data on how many column volumes of what mobile phase show what concentration of TFA with a MS after TFA was no longer introduced to the column? Is it dependent on how long the column was run with TFA, or the TFA concentration? What column gave the data?
Of course, I figured that there must be some interaction, "physical" or "chemical", but what?

Hans, I haven't systematically investigated this behavior due to time constraints, but it would be useful to have such information. My "experiments" were more like: "Column still shows lots of TFA background after flushing with non-TFA mobile phase. Continue flushing. Go to lunch. Come back from lunch. Check background...." etc.

JMK,
Did you get my message? I was unable to open you attachment with structures. Would you please send it again in PDF.