Chromatography Forum

I recommend using Formic Acid if you are having trouble with TFA!

blackdrum already stated that formic acid is not working for his applications

Kostas, I am not sure that mixed-mode will work if you use formic acid. BD has compounds with several nitrogens according to his post and FA does not create enough ions to facilitate elution (assuming that nitrogens are basic and not neutral like in amides). In mixed-mode you can use any ions, just need to watch for pH and ionization state of stationary phase and compound. In cases like this we (SIELC mixed-mode) are using ammonium formate which will create much more ions. Question is how stable is product and how easy it is to remove AmFM on a large scale prep run.

I guess I was thinking in terms of analytical chromatography where you can increase the % of formic acid as much as needed, but I guess that is impractical in preparative chromatography... I see also your point of pka differences and H+ available to be able to elute something from the column

Vlad and Kostas,

Thank you.

We have a lot of compounds in this library, so a general method is necessary, I prefer to make some changes on C18 columns, next step I'll add small amout HCl in FA, and evalute the separation result. Polymer column is another choice, it works well at high concentration HCl, but my application on other project shows this kind column doesn't have compatible capacity as C18 column.

I have used TFA for a separation on our LCMS. I tried to run in negative mode after this analysis and the sensitivity is down. What is the best way to clean the system after using TFA?

a MS can be cleaned of TFA by running lots and lots of mobile phase that does not contain TFA through it.

TFA is acceptable to use in MS, this much is true, however it does indeed result in respose suppression.