Which acid or base additive should I choose for positive vs. negative ion mode in LC-MS? – FAQ.

You should choose ammonium acetate or formic acid depending on whether you’re doing positive or negative ion mode. If it is positive, then 0.1%  formic acid is best, if negative then 10 mM ammonium acetate. We suggest not exceeding 10mM ammonium acetate.

With HILIC type columns, you may need to use a significantly higher concentration and this is one of the advantages of Cogent TYPE-C Silica™ in Aqueous Normal Phase (ANP). Buildup of ammonium acetate on the MS nebulizer occurs quickly with higher concentrations. When using 10mM, you will still have buildup but you will not need to do the cleaning nearly as often as with a higher buffer concentration.

Also be sure that your B solvent contains at least 5% DI water for solubility reasons. The only time you would generally use both ammonium acetate and formic acid together is if you want a pH gradient, in which case you would do this with one binary solvent but not the other.