GC Headspace on ointment

[mac]

Hi all,
I'm trying to develop a method for analysis of residual solvents in an ointment using GC headspace. The ointment consists mostly of vaseline and paraffin oil. My question is, how should I go about preparing the sample for analysis and what kind of standard should I compare it against. My plan was to use a known volatile substance like Toluene as a standard. I obviously can't spike this directly into the ointment and the ointment will only dissolve in hexane or other similar solvents which overpower the chromatogram their gas is injected. Any ideas?
Thanks a million!

[chromatographer1]

First I would like to know the solvents you seek to measure as this affects any procedure you might wish to implement. For example: if you are measuring methanol or ethanol, then that has a LOT of bearing on any proposal that may be offered.

Assuming that methanol is not an analyte of interest:

First determine if you make add reproducible amounts of ointment into vials.

Assuming you can:

Make spiking solutions of the analytes of interest,

let's say you want

1. acetone 2. isopropanol 3. toluene 4. methylene chloride 5. MEK 6. chloroform

dissolved into methanol

Make standards by taking your 'grease' aka ointment, and weighing out reproducible amounts into each vial, 100 mg, at most 250 mg..

Then add 5 microliters of your spiking solution into each of 5 vials, closing each vial immediately after the solution is added.

Test the headspace after heating the vials for at least 5 min at 80 degrees and see if you can get reproducible results.

If you can, then make up different concentrations of spiking solutions to determine linearity.

If methanol is unacceptable then use another solvent which can contain all the analytes of interest should be substituted.

Give more info and I may be able to give better advice. I have done residual solvents in stearamide for example. I even did zinc stearate.

best wishes,

Rod

[Peter Apps]

You know of course that the ointment itself will give you a lot of headspace organics.

Peter

[mac]

Thanks for your replies.
The method I am trying to develop is a general test for any residual solvents that may be present. I was hoping to use Toluene as a marker peak.
There are, as Peter suggested, a whole series of small sample peaks present all along the baseline when an injection is taken from a 10mL vial with just 100 - 500mg of sample in it or with 5mL water on top of sample. Any peaks of significant size would be investigated and identified but so far all the peaks are very small with areas of 1.2 or less. There is even a small peak at the retention time of toluene which may cause difficulties with quantitation of spiked samples (It is a possibility that there are traces of Toluene in the sample).

I have tried spiking 5uL amounts of 1000ppm and 100ppm Toluene in 50/50 ACN/water into vials on its own and into vials containing 500mg sample and the areas have proved non-reproducible with % RSD results of over 10%. What kind of % RSD would be acceptable for this type of assay?

The Headspace settings that I am using are:
Incubation Temp 85C
Transfer line 110C
Loop 110C
Incubation time 60min
Agitation high
Vial pressurisation 0.4min
Loop fill 0.08min
Loop equilibration 0.2min
Sample inject 0.5min
Oven stabilization 1min

The Headspace is an Agilent G1888

Thanks again

[krickos]

Hi

Well lack some detail like the GC setting, column split flow etcetera, but will have a go at the headspace parameters in general.

The Headspace settings that I am using are:

Incubation Temp 85C- might be too high especially if water is present in significant amounts, vapor may spoil sensitivity and precision, usually try to avoid above 75-80°C with water
Transfer line 110C
Loop 110C
T-line and Loop, well hard to tell depending on whats in the sample and if any polar high boilers may be present, as a precaution as you have unknows I would consider raising the considerbly like 180/190°C respectively to avoid any contamination of valve/loop/needle


Incubation time 60min-fair enough as you are screening but can be reduced when you have better info
Agitation high-do not hurt
Vial pressurisation 0.4min-What is the setting for vial pressure?
Loop fill 0.08min-In my experiance set to short for Agilent instruments below 0,15min you may have issues 0,20min should do better
Loop equilibration 0.2min-depend on loop size if standard 1ml I would set it to 0,05min
Sample inject 0.5min-Normally OK but depends on how your total flow looks like versus loop size, if for instance it is a EPC set up where the total flows go through HS and splits up like column 2ml/min and split 10ml/min the loop is flushed OK.
Oven stabilization 1min-OK

As for RSD% in general I would expect a RSD below 10%, pharmacopiea genereal procedures tend to accept a RSD of 15% which might be OK for trace limit test analysis of like 2ppm benzene but at 500-1000ppm level of toluene which have a good response on FID I would expect better.

Using water on top on the sample. Well I have mostly seen failures regarding water and toluene performance wise, technically you can dissolve some toluene in water but considering your settings you might have quite unstable partion coeffient bettwen liquid/gas phase (more or less completly forced to gas phase and the vapor issue). You could consider using an aprotic solvent such as DMF/DMSO unless those are likely to be present, that way you can keep headspace oven at like 70-80°C and have a more stable partion coefficient as those sample solvents retains toluene better.