USP Residual Solvents No HS

[cody84]

I don't have any experience with headspace and we don't have the equipment here. Is there any way to convert headspace methods to non-headspace? I'm guessing it would mostly just be in sample prep because we use the same column and a very aqueous sample prep to test for IPA and EtOH currently.
Just wanted to run it by you guys before I order standards and attempt this.
Thanks

[rwjohnson]

I know of somebody that made his own headspace sampler with a heating block, tubing, and some valves. It works really well and we still use it today even though we have very nice equipment.

Ron J

[krickos]

Hi Cody

As both solvents are class 3 solvents you do not need to specify them individually on release testing ie a simple loss of drying test (NMT 0,5%) will do.

I f you want to monitor them individually lets say as a IPC during drying of a drug substance, go ahead and try a liquid injection. 'It really depends on the substance, some is doeble some are not.

Edit:
As you say, the same columns may be used as for HS, but the challange is the sample prep and the sample. Some substances will degrade in injector and interfer with your analysis.

Some substances depending on concentration may remain in glass woool and interfer with injections after the first sample injection.

For IPC drying monitoring we sometimes have done the calibration, then inject sample. If drying is not complete, liner is changed and calibration rerun while drying continues.

If you need to try this, I would suggest that you initially keep sample concentration low, maybe start with 0,05-0,1g to 10ml to minimize potential liner issues, and if water is used not more than 0,5µl injections.
As class 3 solvents specification is 0,5%, you normally do not need to go for a very sensitive procedure like below 0,1%.

[cody84]

I have to test for methanol a class 2 as well as IPA and 1-butanol (class 3's) in a liquid raw material. So loss on drying won't work for this.

The ethanol and IPA I mentioned earlier are actually actives in one of our products.

I may just try to apply our current method for those two to this raw material and see what happens. I know methanol shows up well because QC uses it as a syringe wash...so it shows up all the time.

[walter]

If you have some headspace vials, SPME fibers with a holder and a stopwatch you can do headspace SPME manually and economically. It should work well for the solvents you are interested in. Look in the Supelco catalog and you should find everything you need.....no, I don't work for Supelco.

[cody84]

thanks walter I'll have to look into it. Do you think a QC lab would be able to perform it on a regular basis with consistent results though?

[walter]

For the best precision the application would need to be automated, which can get expensive. However, acceptable results can be obtained if the temperature and equilibration time are carefully controlled.