Chromatography Forum

I want to know a good and accurate method of detecting Dimethylformamide as residual solvent in Drug Subetances which are water insoluble, using Head Space GC technique.
I am facing some problems in convincing Chinese drug authorities that Head Space method is okay for DMF detection.
Their argument is that since the BP of DMF is 156°C, and Equilibrium temp of the oven in Head Space is usually 80°, DMF may not get extracted fully from the drug substance specially when the drug in question is water insoluble.
Can any body address this issue.
Can I use a higher oven temp for extraction (156°) of DMF and can I use any other solvent in place of water for dilution

Dr. Arun Malhotra

Dr. Malhotra-
We routinely test for DMF by headspace in our lab. 80C is in fact too low a temperature so I recommend using a higher boiling solvent for your API. We use DSMO or Benzyl Alcohol depending on solubility of our API's. We run our HS oven at 140C, which I realize is below the DMF boiling point but we get acceptable precision (<2%RSD) and recovery (95 - 105%) when spiking from LOQ to 120% of our specification limit. You don't necessarily have to have 100% partitioning in order to achieve acceptable results; in fact you never will acheive exactly 100.0% efficiency. Good Luck.

-Jeff

Try USP or EP method...