Impurity detection via GCMS

Discussions about GC-MS, LC-MS, LC-FTIR, and other "coupled" analytical techniques.

14 posts Page 1 of 1
Hi all,

I was running an impurity analysis on a technical grade material of L-Carvone - 10 separate batches with purities ranging from 93.00% to 99.27%.

The technical grade material is synthetically made and I would image that if I have a purity of 93.00%, there should be a significant amount of other "stuff" compromising that 7% that I would detect on the mass spec.

Specifically, the supplier does their own analysis and usually finds the following impurities: dihydrocarvone, carvenone, and cyanocarvone. They are found at concentrations between 0.01 to 0.3% depending on the impurity.

Now, when I look at these molecules, they are very similar to my main compound in structure and have very similar physical properties. My question is sort of general - mass spec is my weakest subject - but if I am unable to separate these impurities from the main compound on the column, and they elute into the mass spec at the same time, will the sheer higher relative concentration of the main active ingredient "overshadow" the fragmentation spectrum of these other possible impurities? My chromatogram only shows one peak but the fragmentation ion spectra at different parts of the peak look slightly different but not enough to give me a different match in the library.

Due to time constraints, I was forced to follow the method supplied by another lab (column, parameters, etc... were all identical to what they ran). I have a feeling the column I am using, ZB-FFAP is not able to separate these molecules on the column properly. I find it very strange that I see only one peak on my chromatogram when the supplier (not the supplier of the method, but the chemical supplier) has shown impurities up to 0.3%.

Thanks for any help!
You need to find reference spectra for the suspected impurities and see if you have unique ions present that you can use to quantify each one. If a mass is shared between two or more analytes, then you have to separate them on the column or you will not be able to quantify accurately.
The past is there to guide us into the future, not to dwell in.
James_Ball wrote:
You need to find reference spectra for the suspected impurities and see if you have unique ions present that you can use to quantify each one. If a mass is shared between two or more analytes, then you have to separate them on the column or you will not be able to quantify accurately.



Thanks James, I kind of figured that would be the case. Do you have any suggested online library of ion spectra for various compounds that you would recommend using?
I agree with James. I have found this very useful:

http://webbook.nist.gov/chemistry/

your impuruties show a nice m/z = 152 molecular ion and your carvone is only m/z = 150. There are other ions in the spectra by which you can sort your data to check for coelution.

I'd be surprised if you can't separate these 3 from each other on a wax phase. Have you reproduced all of the analysis conditions that the other lab uses? Be careful you're not blowing all of the impurities out the split vent.
rb6banjo wrote:
I agree with James. I have found this very useful:

http://webbook.nist.gov/chemistry/

your impuruties show a nice m/z = 152 molecular ion and your carvone is only m/z = 150. There are other ions in the spectra by which you can sort your data to check for coelution.

I'd be surprised if you can't separate these 3 from each other on a wax phase. Have you reproduced all of the analysis conditions that the other lab uses? Be careful you're not blowing all of the impurities out the split vent.


I'll check out that website, thanks for the reference. I definitely see that the impurities I'm looking for all contain a 152 m/z ion, but this molecular ion is not present at all in any of my samples.

So for now I'll have to troubleshoot and determine why the supplier of the material is seeing these impurities but I'm not. As you mentioned, could be the column - which is what I'm leaning towards. The lab supplied method we're using didn't come from the supplier but a 3rd party who performed impurity identification on this material as well (they didn't detect any impurities either but they used different batches) so now that I'm seeing I didn't detect any impurities either, on material the supplier says there are impurities, I think it is more of an issue with their column selection and methodology than it is with the impurities not being present.

Thanks for your help!
Lets say your detection limit is 0.1 ng. To see an impurity at 0.3% (which is the highest level that the supplier reports) you have to have 333 times as much of the main compound, or 33 ng. This is a pretty big peak for the main compound - check the concentration of the sample you are injecting, the injection volume and the split ratio to make sure that you are putting at least that much onto the column. For the minor impurities you need correspondingly more main component to see the impurity peaks.

Peter
Peter Apps
Peter Apps wrote:
Lets say your detection limit is 0.1 ng. To see an impurity at 0.3% (which is the highest level that the supplier reports) you have to have 333 times as much of the main compound, or 33 ng. This is a pretty big peak for the main compound - check the concentration of the sample you are injecting, the injection volume and the split ratio to make sure that you are putting at least that much onto the column. For the minor impurities you need correspondingly more main component to see the impurity peaks.

Peter



Thanks for the reply Peter. I'm using a splitless injection, so I'm not too worried about the split ratio. I will have to do some trouble shooting, so I will look at my sample concentration and injection volume for sure. Right now I am currently injecting 1uL at a concentration of 2mg/mL of my main component - so I am injecting 2ug of main component into the system.
With 2 ug on the column you might be getting serious concentration overloading that buries your impurity peaks under the main component. You might need to use a different stationary phase.

Peter
Peter Apps
Peter Apps wrote:
With 2 ug on the column you might be getting serious concentration overloading that buries your impurity peaks under the main component. You might need to use a different stationary phase.

Peter



One thing I noticed with the supplied method I was given - after the running the analysis of course - was that the column they used for the analysis of the purity of the main component was done using a polar stationary phase, while the impurity identification analysis was performed using a nonpolar stationary phase. Changing the stationary phase to a polar stationary phase or using a column designed for chiral separations was one of the first things that came to mind to play around with. I'll definitely be looking into that.
Zoraku wrote:
Peter Apps wrote:
With 2 ug on the column you might be getting serious concentration overloading that buries your impurity peaks under the main component. You might need to use a different stationary phase.

Peter



One thing I noticed with the supplied method I was given - after the running the analysis of course - was that the column they used for the analysis of the purity of the main component was done using a polar stationary phase, while the impurity identification analysis was performed using a nonpolar stationary phase. Changing the stationary phase to a polar stationary phase or using a column designed for chiral separations was one of the first things that came to mind to play around with. I'll definitely be looking into that.


One column to identify and another to quantify - now why would they do that ? I wonder. The FFAP column you have is very polar - try a methyl silicone or 5%phenyl column.

Peter
Peter Apps
Sigma have an application for the enantiomers of Carvone. Any use?
https://www.sigmaaldrich.com/technical- ... rvone.html
Peter Apps wrote:
Zoraku wrote:
Peter Apps wrote:
With 2 ug on the column you might be getting serious concentration overloading that buries your impurity peaks under the main component. You might need to use a different stationary phase.

Peter



One thing I noticed with the supplied method I was given - after the running the analysis of course - was that the column they used for the analysis of the purity of the main component was done using a polar stationary phase, while the impurity identification analysis was performed using a nonpolar stationary phase. Changing the stationary phase to a polar stationary phase or using a column designed for chiral separations was one of the first things that came to mind to play around with. I'll definitely be looking into that.


One column to identify and another to quantify - now why would they do that ? I wonder. The FFAP column you have is very polar - try a methyl silicone or 5%phenyl column.

Peter


I didn't really think much of it, using a polar and a non-polar column at the time, but after not seeing any significant separation of any compounds on the GCMS I started to question it. Especially that when I run the GC-FID analysis there does happen to be a few small peaks separated from the main component. I will give one of those types of stationary phases a try. I would imagine if you can separate components for quantification during FID - why not use the same column for the MS portion?
Andy F wrote:
Sigma have an application for the enantiomers of Carvone. Any use?
https://www.sigmaaldrich.com/technical- ... rvone.html


Thank you for this Andy. I have seen this before, and while it is certainly interesting, I would prefer to not put any more money into this project (purchasing the Chiral column) than I already have. I already get a lot of flak for the amount of money I spend around here and with the year ending, there isn't anything in the budget for me to spend - even a few thousand for a new column. I have a few GC columns already that I will be able to work with (we don't use a lot of GC or GC/MS analysis around here, so I have limited funds and supplies to work with at the moment).
Can I make a suggestion without spending any more money? Try split, say 50:1. Then try SIM as well for 152. You can then at least establish presence.

To give you an analogy, ASTM 5501 measure 0-3% or so impurity in ethanol. Big split to minimize the tailing of the ethanol peak, get a much nicer peak. Then the other components will separate better. If you do not see impurities with split, then move to SIM mode.

Best regards,

AICMM
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