Chromatography Forum

Hey There

So over the years I recall hearing that there may be problems with using formic acid as a modifier in a mobile phase that contains methanol.

I think the main concern was formation of methyl formate.

I guess I'm wondering how much of a problem this really is. If small amounts of methyl formate are formed, so what? Does it really matter? Is the concern that the UV cutoff or back ground absorption might increase somewhat? Or is the concern that there may be an artifact peak: in either UV or Mass Spec?

I am interested to understand this issue a little better, as we use this combination a lot in our lab.

Thanks very much in advance for any help.

Adam

I think that concern is not formation of ester but rather consumption of formic acid. This might be very critical if your column and analyte have ionic properties, because retention time of such analytes will start shifting.

Hi Vlad

Can you please explain. If the ester is formed you would lose (or consume) some formic acid. But I think you're referring to something different.

If by "consumption" you are referring to something other than conversion to methyl formate, can you please explain what it is that you're referring to.

Much Thanks!

you will "consume" formic acid by converting it to ester. If you are analyzing basic analytes it might affect peaks shape and retention, lets say if you are even using regular RP column and have some IE coming from residual silaniols. if you are using mixed-mode columns where IE is much more pronounced you will see drastic increase in retention time of basic analytes in case of exchange mode and reduction of retention in case of exclusion mode. Ester formation is not going to affect the strength of your mobile phase in terms of hydrophobic properties, unless you are using huge amounts of formic acid (3-5%).

OK, so we are both talking about the same thing: conversion to methyl formate.

So one last follow up. You mentioned bases, but wouldn't this be more of an issue for anion exchange separations. I'm thinking that as the conversion happens, we get less formate anion which could make the mobile phase weaker in an anion exchange separation (whether or not in mixed mode).

Am I correct or am I missing something.

Much Thanks

Hi,
There is nice publication in LCGC North America about stability of formic acid in methanol solutions.
http://connection.ebscohost.com/c/artic ... n-analysis

Best Regards
Peter

In RP you can only have cation-exchange coming from residual silanols, unless it is polar-embedded column, which underwent hydrolysis and there are some amino groups on the surface. In mixed-mode it can be both, cation- and anion-exchange as well as both exclusion modes. In all this cases depletion of ions produced by formic acid will cause shift in retention.