Acetic acid and Formic acid Residual solvents USP <467> GC-FID HSS

Wondering if anyone has experience detecting acetic acid and formic acid using GC-FID HSS. I am trying to develop a method based on the limits described in USP <467> of 5000 ug/mL of each of the two solvents, but having a hard time seeing any peaks.

  • I read the document, but I couldn't see what they dissolved. And I also have the doubt if it is liquid injection or headspace. Have you tested on it?
  • The analyses demonstrating the DB-624UI, in the application note 5991-0845EN are showing direct injections of Free Fatty Acids standards, that are dissolved in methylene chloride. The purpose and most notable achievement is that the DB-624UI column is capable of performing this chromatographic separation. The GC analysis of free fatty acids (e.g., formic acid, acetic acid) has usually required the use of a specialized GC column coated with FFAP (i.e., Free Fatty Acid Phase), that is chemically treated to be slightly acid.  The reason is, that the acidic nature of free fatty acids make it very difficult to see good peak shapes due to absorption of the acids inside a non-FFAP column. While a FFAP column does a very nice job for the GC analysis of free fatty acids, these FFAP columns are limited in terms of being suitable for use in the broader range of polarities that one can encounter in all other GC analyses. The DB-624UI, however, is able to achieve excellent inertness for free fatty acids, but is also especially suited for the broader analysis of volatile organic compounds of all types of polarity, and thus would be an excellent choice for use in the USP<467> analysis. This is the primary purpose of this application note.

    To the question of would formic acid and acetic acid be amendable to GC-FID analysis, using a static headspace injection, the short answer is yes, but with great difficulty.  Both of these carboxylic acids present difficulties that make their quantitative analysis by static headspace very challenging, even though these are listed in the USP<467> monograph as Class 3 solvents. 

    There are too many variables that would need to be addressed as suggestions towards optimizing the <467> static headspace methodology for these 2 specific analytes for this forum. Might I suggest that you take a look at this reference (below) to see what other pharmaceutical regulatory agencies have adopted for the broad scope of analytes that are targeted in APIs. You might be interested where the article discusses a direct inject technique of residual solvents that have high K (distribution constant) and thus poor recoveries when applied to static headspace injections.  I would also recommend that you call Agilent Technologies, and seek assistance directly with one of our very experienced GC columns, applications chemists. 

    Witschi, C., Doelker, E., (1997). Residual solvents in pharmaceutical products: acceptable
    limits, influences on physicochemical properties, Eur. J. Pharm. Biopharm. 43, 215-

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