Chromatography Forum

I have a bulk pharmaceutical that I believe has crystallized as an hemi-ethanolate. I need to be able to quantitate the amount of ethanol present in the bulk material as part of the characterization. I haven't done any GC work for a long time so I'm not sure where to start. Any suggestions on sample prep, instrumentation, etc. would be greatly appreciated.

Thanks,

KarenJ

Hi Karen,

Can you tell us what equipment you do have?

Regards,

Ralph

Is your bulk material water soluble or not? What levels of ethanol do you expect?

Best regards.

Hi,

I will be borrowing an instrument in another lab. I haven't seen the instruments yet but I've been told that they have several GCs and the detector types include FID, NTD, ECD, and MS. I don't know a lot of other details about the equipment except that I know that they do not have a headspace sampler.

The drug compound is poorly water soluble. It has pretty good solubility in IPA and EtOAc. The compound is expected to contain about 5.4 wt% ethanol.

Thanks,

Karen

A simple prep would be to dissolve into IPA or EtoAc and add an internal std (methanol or IPA) at about a 0.1% level (1mg/mL). Dissolve the matrix at a 2% (20mg/mL) level. The FID response of methanol to ethanol is corrected by a factor of 1.37 or so.

Use a packed column of Porapak or Hayesep Q, an injector temperature of 180°C, a column temperature of 170 to 180°C and a flow rate of 20-40 cc/min.

Use a plug of solvent behind your sample plug in your syringe and try not to inject more than 1.5µL total if possible.

best wishes,

Rod

If you dissolve the sample in IPA, make sure you run a blank injection of IPA to check it for ethanol content.

I would be tempted to dissolve the sample in DMF and run it on a capilliary DB624.

GCguy

I would be tempted to dissolve the sample in DMSO and do the analysis by headspace with FID. The ethanol should headspace pretty well, the sample matrix and much of the DMSO gets left behind.

Best regards.