Headspace GC test method for 2-methoxyethanol in API

[Terry]

Hello all,

I am trying to develop a Headsapce GC test method for 2-methoxyethanol, as it is out of the scope of specified in USP <467> for its high boiling point (125 degree C).

Anyone has some hands-on on this issue?

Thanks in advance,

Terry

[chromatographer1]

This should not be a difficult solvent to test for.

Have you made ANY attempts so far to measure it in your API?

Tried to partition it from any solvent in which your API soluble ?

from Water?

from DMAc?

from dilute mineral acid? base?

This should be no more difficult than butanol as long as you do not use an excessive amount of sample in the vial. Keep your vial temperature below 85°C and your sample size less than 100 mg (assuming you are measuring less than 1% of the solvent)

An hour in the lab is worth a week waiting on the web forum.

best wishes,

Rod

[Karen01]

This should be no more difficult than butanol as long as you do not use an excessive amount of sample in the vial

I agree. That should be easy. Just try it wit ha solvent that optimally dissolves the API and is higher boiling that the analyte. You don't even necessarily have to dissolve the API as long as the solvent extracts the analyte efficiently from the API, though that is more work to develop and validate.

- Karen

[Alchemist5]

I have come to a similar project. For us, though, we can develop a liquid or headspace method. However, our issue is that the sample (Chlortetracycline Bisulfate) contains up to 15% butanol (See USP monograph). Most reference chromatography shows that butanol elutes slightly before 2-methoxyethanol. If butanol is present in the sample around 15% and we are looking for the ICH level of 2-methoxyethanol (50 ppm), I don't expect good separation. the small 2-methoxyethanol peak will probably elute on the massive tail of butanol.

As of now, I don't know the solubility of chlortetracycline bisulfate in various solvents. Protic polar solvents may reduce the sensitivity of 2-methoxyethanol (like water or other alcohols).

My question, I guess, is if anyone knows of any technique that can help separate these two components better or suggest a type of GC column phase. I am going to start with a WAX phase (G16, 30m x 0.32mm x 0.25µm).

Hope I can see my peak not interfered with by the butanol peak.

Burt

[chromatographer1]

backflush to vent multidimensional app should be an easy fix.

heart cut with only using a tight post peak setting would also work well and get rid of the excess butanol so separation can be achieved. Could switch valve manually if operator is coordinated enough.

takes only one valve, can use cap columns

I see separation on 5% phenyl, 1301, and Wax columns.

best wishes,

Rod

[Alchemist5]

Hi Rod,

Wow, these are techniques I know little about.

Reading into them a bit, I find that both are multicolumn techniques. The first, backflushing, may not work in my situation as it looks as it is mainly used to remove the higher boiling components of a mixture (such as a high boiling diluent like DMSO, DMA, etc.). The butanol, which elutes before 2-methoxyethanol on a non-polar and on a WAX column, would not be removed by this process from what I can see.

The heart-cut technique looks promising, but the use of two instruments (for in series oven programming) will not be feasible here at this lab. I can, though, set up two columns in series and run a longer isothermal section to elute the two components through the first column and then begin to temperature ramp as they move into the second column. Is this something worthwhile to do? I have not done in series columns before, so I don't know the pitfalls of such an analysis.

[chromatographer1]

The chromatograms I see on line do not match your description. methyl cellusolve elutes before n-butanol on all three columns I mentioned. See Restek's web site.

Rod

[Alchemist5]

The chromatogram I was viewing from Restek was GC_FF00644 where the RTX-WAX does elute methoxyethanol after butanol. The 5%-phenyl is the opposite in order. I like that better. MDGC will be beneficial at that point if I could do MDGC. I'll see if 15% butanol won't mask my little peak with a 5%-phenyl.

Thanks Rod

[chromatographer1]

Sorry I misread the chromatogram. Doesn't the 1301/624 also have the same elution? It would be my preference if you have one.

best wishes,

Rod

[chromatographer1]

Both apps can be done isothermally. I am not talking about a GCxGC app, but the traditional BF or HC which uses Valco or other brand valves without a thermal modulator between columns.

The columns can be of the same phase and ID, etc.

If the butanol elutes AFTER the methyl cellusolve 2MeOxyEthanol (MOE) then backflushing after the tiny earlier eluting peak get rid of most of the later eluting butanol which narrows its width and thus increases the separation between it and the MOE. The negative of this is the issue of the sample which reenters the injector while backflushing.

Likewise using a heartcut, if you have the HC open early and close it just after the MOE enters the second column the same effect is achieved, but the butanol elutes through a second column or to a vent line without backflushing through the injector.

This would be preferred.

best wishes,

Rod

[Alchemist5]

Rod, your explanation is much appreciated.