internal standard weird in DMF

[aceto_81]

Hi,

we regulary use 2-propanol as an internal standard for our residual solvents in our API.
But when we use DMF as a solvent to dissolve our 1g of API, we see our area's of 2-propanol fluctuate over time (it decrease over about 6 injections to about 30% of our reference, and then starts to increase again), really weird.
If we use water as our solvent (in case of water soluble API), we don't see this variation at all.

Our method uses headspace, 80°C for 60 minutes and then inject onto our column, which is a temperature gradient, starting at 50°C going to 180°C.


Anyone some ideas?

Ace

[chromatographer1]

You have chemistry going on.

Without knowing the matrix and the different solvents under investigation, as well as the physical composition of the seal materials, that is about the limit of any explanation.

It behoves you to add water in some amount to your vials to see if that will stop the chemistry.

This will only improve your recovery of the solvents and may prevent the change of IPA recovery.

best wishes,

Rod

[aceto_81]

Thanks for your reply.

matrix = API's and some pharmaceutical excipiens
different solvents = methanol, ethanol, acetone, 1-propanol, benzene, ... some more residual solvents.

We use 1g API + 10 ml internal standard (about 99.9% DMF, and 0.1% 2-propanol) in a 20ml headspace vial, sealed with a PTFE/silicone septum.
In case of water soluble API's, DMF is substituted by water.

How many water do you think is needed? Are we talking about 1ml/ vial, or more/less?

Ace

[chromatographer1]

I would use as much water and as little DMF as possible.

But if chemistry is prevented by less water and this is your wish, then by all means do so.

It is a shame you are trapped using such old and difficult method parameters.

1000 mg and 10mL of dissolution solvent ! And heating for 60 min when 10-15 min is required. Of course using so much material makes an extended heating time necessary.

I was able to accurately determine 1 ppm of solvent using 1mg of drug, using 25 microliters of dissolution solvent in a 3.35mL vial. 2mL, 6mL and 10mL vials are available for HS analysis, besides the 20mL vials you are using.

But use what you must. I would NEVER use more than 100 mg and 0.25mL in a 6mL vial.

And heating more than 15 min actually decreases the recovery of the analytes due to interactions like you have experienced.

But what do I know?

best wishes,

Rod