Formic acid by HPLC

[GregK]

I have been tasked with determining the residual formic acid in a raw material, povidone. The USP does not list a procedure for formic acid assay (at least that I could find). The EP does list a formic acid test that I think we could do, but I have zero experience with ion-exchange. The EP calls for "strongly acidic ion exchange resin r" in both a prep column and the LC column. I've been trying to find info online for purchasing these, but to no avail.

Any help? I'd love someone to just give me the part numbers and vendors, I can figure out how to run it from there.

Thanks in advance.
-Greg

[dorota]

Journal of Pharmaceutical and Biomedical Analysis
Volume 41, Issue 3, 7 June 2006, Pages 738-743
Simultaneous determination of formic acid and formaldehyde in pharmaceutical excipients using headspace GC/MS

Abstract
Formic acid and its esters, as well as formaldehyde, are trace impurities that are often present in pharmaceutical excipients. These trace impurities can potentially react with amino and/or hydroxyl groups in drugs to form significant levels of degradants. To select the appropriate excipients for a stable formulation, a gas chromatography/mass spectrometry (GC/MS) method was developed and validated for the rapid screening of trace amounts of residual formic acid, its esters and formaldehyde in pharmaceutical excipients. Samples were dissolved or dispersed in acidified ethanol to convert formic acid and formaldehyde to ethyl formate and diethoxymethane, respectively. Identification was conducted using a GC/MS system under scan mode and quantified using a selected ion monitoring (SIM) mode. Evaluation of the mass spectra of ethyl formate and diethoxymethane in the samples indicated that the method is specific. The limits of quantitation of the method were 0.5 ppm for formic acid and 0.2 ppm for formaldehyde. The precision of the method was demonstrated by the acceptable R.S.D. (≤10%) over a linear range of 0.5–10,000 ppm. The accuracy of the method was within 80–120% over the linearity range. The amounts of formic acid and formaldehyde in commonly used pharmaceutical excipients is reported.

[tom jupille]

That's probably a BioRad HPX-87H or equivalent (sometimes referred to as "ion exclusion" column). They are available from most major manufacturers. Do a Google search using 'hplc "ion exclusion column"'.

[Consumer Products Guy]

Formic acid assay is straightforward by HPLC (sodium formate is sometimes added to consumer products). Typically for organic acids we use dilute sulfuric acid (0.005 N or less) as eluent, and HPLC columns designed for organic acid analysis. We formerly used ion exclusion columns but much better are the more-modern columns designed for organic acids like Grace Alltech Prevail Organic Acid or Restek's version. We use conductivity detector, or sometimes low wavelngth UV. Some of these organic acid assays we have also validated ourselves.

[adam]

I wonder how these organic acid columns work (what is the phase).

I know the companies don't disclose this, but does anyone know exactly how these columns work.

Thanks

[XL]

I believe Grace Alltech Prevail Organic Acid and Restek's version of Organic Acid are reversed-phase HPLC columns. The retention mechanism is hydrophobic interaction in ion-suppression mode (at low pH). This way highly hydrophilic organic acids like formic acid can be retained a bit more compared to that at higher pH. The mobile phase is usually 100% aqueous to enhance retention. You can also get the similar type of column from other manufacturers, such as Acclaim Organic Acid from Dionex (http://www.dionex.com/en-us/products/co ... 71770.html).

When you read carefully, you will realize that formic acid is only weakly retained (k'<1) on any reversed-phase columns. To overcome this problem, you can consider using reversed-phase/anion-exchange mixed-mode columns. Acclaim Mixed-Mode WAX-1 column is one option. As you can find in Figure 7 from http://www.dionex.com/en-us/webdocs/488 ... 021407.pdf, this column can retained and separate a suite of organic acid including formic acid very well. In this case, the retention mechanism is anion-exchange superimposed by reversed-phase interaction.

When detecting organic acids with UV, the wavelength is usually set around 210 nm. Even so, from my firsthand experience the sensitivity is around 10 ppm level. If higher sensitivity (e.g. ppb level) sensitivity is required, you will need to use ion chromatography with suppressed conductivity detection. Related information can be found in the following link: http://www.dionex.com/en-us/products/co ... 73257.html.

I hope above information helps.

[Consumer Products Guy]

I wonder how these organic acid columns work ...

I don't. I need to get practical results, efficiently, and quickly. And there's also much more ahead to do.

I leave the "total understanding" to the PhDs, while I get the results out....

[Karen01]

I wonder how these organic acid columns work ...

I don't. I need to get practical results, efficiently, and quickly. And there's also much more ahead to do.

I leave the "total understanding" to the PhDs, while I get the results out....

In many cases no one has total understanding,but I think having some understanding of the retention mechanism(s) involved helps a lot when developing a method and understanding and dealing with the unexpected while supporting product development. I don't have a PhD but I have spent much of my career in R&D and that has helped me out. I aways want to know what the stationary phase is and how it works.

- Karen

[Bintang]

Sometimes actually understanding what you are doing is a great advantage, when the results are "interesting".

My favourite article on the subject (on a guy who should have had a Nobel prize).

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC150444/

[Bintang]

I got so carried away I forgot to mention that HILIC works like a daisy for small organic acids.

http://www.sequant.com/files/documents/ ... c_Acid.pdf

http://www.sequant.com/files/documents/ ... f_EDTA.pdf

http://www.sequant.com/files/documents/ ... f_EDTA.pdf

[cmilesbaker]

Quick and dirty? I just ordered this today, for USP's new harmonized test for residual formic acid in Povidone (and I do hope it was the right thing). From Fisher:

Rexyn* 101 (H) Beads
Research Grade
Certified
Strong acid organic cation exchanger. Sulfonated polystyrene copolymer, hydrogen form, medium porosity. Active group, RSO3-; ionic form, H+.
Cation Exchange Resin, Ion Exchange Resin

[69011-20-7]

[lmh]

Bintang, thanks so much for the lovely reference.