Chromatography Forum

I have been given the task of analyzing a pharmaceutical raw material for formic acid residual solvent by GC. I have not done this before, and was wondering if anyone out there has had experience with doing formic acid by GC. ( I want to do ion exchange, but my all knowing boss says GC). Thanks for the tips.

I have a little experience - none of it good. Formic acid is almost invisible to an FID (too few C-H bonds). You can detect it by MS but even with a very well deactivated system that elutes the other short chain acids as sharp peaks, the formic acid tails all over the place.

You might be able to use a specialist column, but my advice if you have to do it by GC is to derivatise it. No idea how I'm afraid.

Peter

Formic acid by GC is going to be challenging. IC would definitley be a better way to do this. I have always done this with HPLC with RI. If you have to go the GC route, consider packed columns or at least using a polyethylene glycol phase capillary column (wide bore). There may be some PLOT columns which will work better. You may also want to consider derivitizing the acid with a silylating reagent.

Good luck.

Formic acid in a pharmaceutical intermediate is most likely present as the cation. So you have to treat the matrix to make it a free acid by adding an excess of a very strong mineral acid. Then as a free acid you want to quanitatively elute it through a GC. Or you want to add a derivitizing agent (there are possibilities depending upon the matrix the formic acid is found) and try to separate it from all the peaks generated.

On a scale of 1 to 10 this is a very poor 2. Per previous remarks, HPLC with RI or Ion Chromatography ranks an 8 or 9 for ease and accuracy of results.

Perhaps after $pending $everal thousand dollar$ of wa$ted money trying to develop a poor and non-reproducible method your boss will figure out it is cheaper to do it expediently or to send the sample out for testing.

If you do make the free acid form of formic and wish to analyze by GC, remember it elutes AFTER acetic acid on a FFAP column (if it isn't absorbed by all the active sites in the injector, column, and detector.

Do replicates until your formic acid peak stops increasing and a consistent (if inaccurate) amount is attained.

I wish you luck.

Rodney George

Formic acid assay is straightforward by HPLC using an organic acid column, a conductivity detector, and dilute sulfuric acid eluent. I've never used low-wavelength UV for it myself.

Just for the sake of lowering confusion: Rodney means, of course, carboxylate which is an anion.

Thanks Han. You are quite correct. Glad to see you are covering my back.

FLipped that coin in my mind.

Rod

cjwitt,

There was a presentation at Pittcon in Orlando on in-situ derivatization (in-vial I should say) and subsequent analysis. I will find the abstract and send it to you if you want to contact me. aicmm at flash.net Barring the substantial chromatographic issues with the underivatized constituent, the FID will give very poor response due to the single carbon-hydrogen bond. The AID will also give relatively poor response (but better than an FID) with the IP being around 11.3. You might also consider a methanizer if you have one available (I have a friend who has made this work.)

Best regards.

Can we do HPLC analysis with C18 reverse phase of formic acid in the presence of sodium bicarbonate using 10mM phosphate buffer of pH 2.0

Can anyone suggest me how to determine formic acid/ formate in bicarbonate solution with HPLC ( column and other detials)?