Chromatography Forum

We have to analyze one drug substance for diisopropyl ethyl amine content by GC.As it is not a ICH listed solvent, up to how much concentration it is permited
to be present in a drug substance.

Talk to your regulatory people in the company.

They have or should have that information.

Rod

Well

I would not count on the regulatory people alone in this case as the diisopropyl ethyl amine is not listed in the ICH guidelines. I think you will need put some serious effort into justifing the use and specification of residuals of this solvent in your drug substance (availeble tox data, how much can it practicly be reduced in process, max dose per day, is there any regulatory precedence etcetera). I expect that you will have to wrestle a bit with regulatory authorities around this one.

So it is obviously very hard to give a recommendation, but if someone told me just analyze the stuff, I would consider going very low and try to treat it as a class 1 solvent for time being ie try to get close to 1µg/g (1 ppm) levels. Starting at higher levels for other amines like those for pyridine or N-methylpyrrilidone might just cause you having to redo it later as most authorities usually expect that you have reduced an unclassified solvent as far as possible and consequently you need detailed data.

Thank you very much.

The ICH has guidelines concerning new or undocumented solvents.

You may assume as a gross assumption that the toxicity of DiPEA will be similar to TEA. Assume at your own risk of course.

My initial point which was not made strongly enough is that you should be on the same page as your Regulatory people. If you are they, then you need to read the ICH guidelines and fulfill all the legal requirements they and the governments under which you dwell insist you meet.

Prison is no place for a chromatographer, and we don't make enough to pay fines, either.

best wishes,

Rod