Acetic acid estimation by residual solvents analysis

Chromatography Forum: GC Archives: Acetic acid estimation by residual solvents analysis
Top of pagePrevious messageNext messageBottom of pageLink to this message  By Bhaskar Reddy.R on Wednesday, August 28, 2002 - 03:08 am:

Dear All,

we are facing a problem with acetic acid estimation by Residual solvents method. We developed a method with best resolution for 8 solvents in N,N-Dimethyl acetamide as diluent. The analyte sample is Pantoprazole sodium API.
When we are spiking the solvents with the solvents, we found that the acetic acid peak is disappearing. Even with 100% spiking we are not getting the acetic acid peak in the expected levels. All the other solvents are eluting perfectly at expected levels.Can you please expain me, what may be the reason for this and why it is happening with acetic acid only.

Thank you


Top of pagePrevious messageNext messageBottom of pageLink to this message  By Rod on Wednesday, August 28, 2002 - 06:05 am:

Thanks for the info you supplied but a lot of details are missing. I will try to guess at the missing details and supply you with an answer.

I assume you are doing direct injection, with or without split.

With packed or capillary columns the answer is the same.

The acetic acid is a reactive analyte.

First of all, you are dissolving your sample in a very basic solvent. Strong organic acid in a strong basic solvent heated in an injection port. Hmmmm

Second of all, you are injecting and depositing your drug into the injection liner and creating all manner of active sites where a friendly acid like acetic might find a home to cling to. Hmmmm

Although if you used a aprotoic solvent like DMSO you might have a chance to measure acetic acid, the second factor will make it very unlikely, or very expensive in time and replacement cleaned or clean new parts.

Headspace won't help here very much, but it is possible if you choose another dissolution solvent and the right hardware/column.

To do acetic acid I suggest IC or HPLC, solutions that can be made to work. Actually NMR works quite well to measure very low levels as long as you do not have a spectrum which interferes. My spectroscopy specialist told me I was nuts until he followed my advice and found out it would work at surprisingly low levels in many drugs we manufactured.

But that happened long ago at another company, but you may wish to try it as well.

Rodney George


Top of pagePrevious messageNext messageBottom of pageLink to this message  By Bhaskar Reddy.R on Wednesday, August 28, 2002 - 08:02 pm:

Thank you for your valueble suggestions Rod! Please find the details you asked.

I am doing direct injection with split.For this analysis I was used RTX-5 column and my sample concentration is 20mg/ml.I am facing the problem when i am injecting sample only. In standard run I am getting acetic acid peak very nicely.During the sample analysis even if i spiked with 5000ppm of acetic acid also i am not getting acetic acid peak in the expected levels.

Bhaskar Reddy


Top of pagePrevious messageNext messageBottom of pageLink to this message  By Rod on Thursday, August 29, 2002 - 06:18 am:

Second factor is the problem if your std works.

There you have it. Good luck and hope something else will give you that determination of acetic acid.

Rodney George


Top of pagePrevious messageNext messageBottom of pageLink to this message  By Anonymous on Wednesday, June 9, 2004 - 07:29 pm:

I have been trialling over a residual solvent method for analysis of acetic acid myself over the past few months and finally have something that I think works. As it is almost two years since your post you probably have found an answer or have given up but I thought I would add to this in case any one else is looking for an answer.

Finally found the following to work in standard solutions.

Use a solvent such as dimethylformamide or dimethylsulphoxide to disolve your drug. Use headspace gas chromatography. Pipette your sample or standard into a headspace vial (10mL for 22.5mL vial). Add 500uL of BF3/methanol. Use a vial temperature of 120C and a thermostat time of 45min which will allow derivatisation of the acetic acid to its methyl ester. Inject the headspace into the GC. Use a BP 21 column. initial conditions are 40C (10 minutes), 10C / min to 200C. you may need to change final temperature and time depending on what other solvents you have present. This method will be affected by presence of other alcohols so you may have to look for ethyl or butyl esters of acetic acid if ethanol or butanol are present. You will not be able to quantitate for alcohols in the same method.

Please respond if anyone finds flaws with my methodology.


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