Chromatography Forum

hi, i m working in a R & D department of a pharmceutical company.

just now i developed a method for quantifying acetic acid for one of our API. The method involved liquid injection and our method was successful and v also have got recovery and all that inshort i have validated that method as well.

but now when i m applying the same method the the potassium salt of the same API, the metod fails. i could not get recovery. it was poor. i took number of trials by modifying the conditions like i made the media acedic by adding 0.01 M HCl in the diluent, i even strengthen the acidity to 0.1 M but it did not work.

so can anyone suggest something, like some change in the current sample preparation technique or some change in the media or anything.

should i mentione any other parameters ?

Thanks
with regards
Dhruv

Welcome to the world of chemistry.

Your results are not surprising.

Acetic acid is done by NMR and by Ion chromatography by most companies. any GC method is very matrix sensitive.

Using a very high injection temperature is probably your only hope, and that can be troublesome if your API is temperature sensitive. Adding formic acid might be a possibility but I would not expect good results.

Yours is not an unknown problem. Without sample prep to isolate the acetic acid first from your strong cation, it may be very difficult to validate by GC.

wishing you the best,

Rod

Hi Dhruv

Do you have to do this by GC ? - as Rod says it is not the technique of first choice for acetic acid.

If you are stuck with GC please post a complete description of what you are doing.

Peter

mr,peter
we are preparing a std solution with known amount of acetic acid in a diluenet(low boiler),with help of autosampler,injecting 1µl std,we are getting very good responce,and we are getting accuracy,recovery too.
but when we analyed the various salt of same API the problem arieses
so plz give some clue about how can we seprate acetic acid from that complex which may formed with salt



regards
sameer

Hi Sameer,

If your only option is to assay the acetate by GC then yes, I often analyse for acetic acid successfully as well with a polar column such as Innowax.

I presume that you have made an aqueous solution of your sample? If so, taking the pH below 3.5 should liberate the free acetic acid, which can then be extracted with hexane/diethyl ether. What you need to do during that extraction is to add a salt (sodium chloride or sodium sulphate) to the aqueous layer so that the acetic acid partitions more favourably into the organic layer.

For quantitative purposes I would extract the aqueous layer 3 times. Dry your extract by adding anhydrous sodium sulphate.

I would also suggest using sulphuric acid instead of hydrochloric acid and avoid having any methanol or ethanol in your system, otherwise you will end up with acetic acid ester. (which may be another approach )

Regards,

Ralph

hi,
thanks for the clue.
actually we thaught that there must be certain pH condition which we need to maintain and we are not.
now we will take some tials by adjusting the pH below 3.5, but as far as i think we dont need to carry out extraction procedure as we are doing liquid injection of the sample soultion as well as the standard soution. so our main problem was to get the free acetic acid in the solution in case of recovery and in case of sample. isn't it ?

ok then i ll inform u bout the results of the trials we gonna take. and once again thank you very much for the clue.

regards,

sameer

Hi Sameer,

I think it would be best to extract the acetic acid.

1. I would not recommend that you inject mineral acid onto your column. From past experience you can ruin it

2. If you inject the acidified aqueous sample, I would also be concerned about reactions that may go on in your injection port , which would lower your recovery.

Regards,

Ralph

I use a packed column methylsilicone on a H3PO4 precoated carrier.
Injector liner packed with H3PO4 coated glass wool works well.
Samples must always be acidified best a non volatile acid which will remain in injector.
But any GC procedure for a free acid the presence of alcohols is a problem as variable amounts of esterification tend to occur regardless of column.
Carbowax columns often tend to result in analyte losses probably due to free alcohol groups FFA columns are carbowax with a substituted terephthalic acid to reduce this effect. Carbowax on a terephthalic precoat was traditionally used for acetic and formic acids

Bob M