GC-MS problem (methanol is converted to formaldehyd?)

[Chacer]

Hello fellow GCers.
I faced with a problem that started recently and suddenly on out GC-MS/MS system.
We are screening for a range of illegal street drugs, but suddenly methamphetamine started acting very wierd.
We usually get one big peak, but now we get 2 small peaks with diffrent masses and a "smear" between them.
We dissolve all our samples in methanol, and we found that methanol is converted to formaldehyd (via the Mannich reaction http://en.wikipedia.org/wiki/Mannich_reaction) in the presence of metal, oxygen and heat/pressure. The formaldehyd reacts with methamphetamine and gives a diffrent product, hence the two small peaks, one methamphetamine and the other methamphetamine+formaldehyd. The reaction seems to be reverseable, hence the "smear" (could someone explain the reacion between methamphetamine and formaldehyd + maybe give me the mass of the product?).
We suspekt that the metal that catalyses the reaction with methanol comes from the injector/inlet/liner.

It is not an option to dissolve samples in other then methanol.

Does anyone have any idea what we could do?
Could we add something that would prevent the formation of formaldehyd but not ruin the rest of the analysis or react with the other drugs?
Any feedback is highly appriciated.

FULL GC INFO ON PAGE 4

Best regards
Chacer

[macgyver]

Don't know about methamphetamine, but ephedrine/pseudoephedrine can react with formaldehyde to form 3,4-dimethyl-5-phenyl-1,3-oxazolidine.
This paper might be useful: http://www.forensics.org.my/img/Article%2003.pdf

The other thing I've seen is the HCl salt of meth can give double peaks/lumpy tailing edges sometimes. They will be the same spectra, so this shouldn't be your problem. The freebase is usually nice and sharp.

[Don_Hilton]

The formation of this reaction product with methanol just started to happen? The first question that comes to my mind is what changed about the time that this change started. Solvents can be contaminated - even new bottles (from bad lots). Did you open a new bottle of methanol? Is it a bottle that has been open for a while, or shared with someone else?

You should not have significant oxygen in a GC inlet to cause oxidation (or oxidation should have been hapening all along) and if metal is an issue, consider replacing seal on the bottom of the inlet.

[Chacer]

It suddenly started happening of the course of 2 weeks and gradually got worse. We have a simular instrument right next to it, and it works perfectly.
Ill check the log to see if someone else made the solvent. But the same solvent is also used on the other GC that shows no problem on the same sample.

Thanks for the paper. Ill look into it. Didnt know about the HCl salt. Ill look into that too.

We called in experts from Agilent and they didnt know what to say. They are gonna let their development team look into it.

Thank you very much for the replys.
Any feedback is highly appriciated.

best regards
Suphi

[AICMM]

You can't replace methanol, you can't lower the inlet temp, then replace the whole inlet. You said it was working before and the one next to it is working, then replace the whole inlet.... I'm surprised Agilent did not say gun brush the inlet (they do say that once in a while) but I would just replace the whole thing with a new one. Perhaps it is the cost of doing business.

Other things you can try, if you don't want to take that leap yet (depends on what it is costing you) is to replace the split vent line and the split vent cartridge. Don is absolutely right about the bottom seal but that should have already been suggested or done by Agilent, if not by you on a routine basis.

Best regards,

AICMM

[HW Mueller]

macgyver, by what mechanim would the HCl salt give two peaks??

[Chacer]

UPDATE

ok we are analysing the freebase and not the salt.
We have replaced the liner and i didnt help.
There is no problem with the solvent, we tried a new bottle.
The oxygen % is 2.4

We will try to change the seal at the bottom of the inlet, didnt think about that, ty.
We have replaces the liner and it didnt help. We will try to replace the split vent line and the split vent cartridge if the above doesnt work.
If all fails, we will replace the whole inlet.

Thanks for all the great feedback.
More is welcome

Best regards

[macgyver]

AICCM, seems a bit drastic to suggest replacing the whole inlet! Don't think I agree with this. Maybe as an absolute last resort, but I would investigate other more likely avenues first.

HW Mueller, don't know what mechanism causes this - active sites maybe? I've seen it mostly happen when the liner needs changing. It's not really two peaks, usually a split top or lumpy tailing edge. The freebase is normally okay. On a clean system, meth HCl is normally a single peak with the usual tailing you get from amines.

Chacer, one more thing to check is the glass wool. I've seen weird things happen with different brands of glass wool. Check that no one has ordered something different without you knowing. Stick with what works.

[aldehyde]

You've replaced the liner, thats good, and you're going to do other inlet maintenance stuff. Good. Leak test your inlet and see if your air leak is coming from there. If not, uninstall the column from the inlet and cap it with a septa. Wait a little while and then check and see if the air leak is still present. You could also try capping off the MS at the interface. If the leak goes away its the interface ferrule, if it doesnt the leak is present somewhere in the MS analyzer.

I would try and get your air % lower if you can, like you said this happened "all of the sudden" and if you know its not the solvent then it is something in the system. Most likely it is the inlet.

I would also try a new syringe, or at least swap it with one you know is good to eliminate it as a possibility (its so easy to confirm that its not the syringe so why not .)

[Peter Apps]

Just an off the wall thought, if the samples are post-mortem they might be contaminated with formaldehyde before they even get to the lab.

Peter

[Chacer]

I forgot to mention that this happenes in the test mix we use on the system as well as all types of blood. However we dont inject the bloood directly for obvious reasons

We did the leak test by capping the collum. This didnt lower the oxygen level. So the oxygen comes from somewhere else. We tightened alll the bolts ect. but the oxygen is still the same...

Thanks for all the good replys
More are welcome
Ill start looking into the diffrent suggestions today.

One more thing. The oxygen leven on the system right next to this one, has the same oxygen level. But there is no problem. And it is ONLY methamphetamine that causes problems...

Best regards

[Chacer]

UPDATE

The seal at the bottom of the inlet has been changed before and after the problem started. So thats not it.

The split vent line and cartridge has also been changed before and after the problem started, we also run splitless.

The liners are same as we always use.

We have recently leak tested the inlet and the results werer accaptable.

The syringe has been changed and it didnt help the problem.


Ill try to upload the Mass Spec so you can see for yourself.

Best regards

[Peter Apps]

There are two steps to the process; first the formation of formaldehyde (presumably from methanol), then the reaction of the formaldehyde with the methamphetamine.

Methanol to formaldehyde can be by oxidation or dehydrogenation. Neither of these typically happen in a GC inlet. The % levels that you see for oxygen are relative to a tuning peak - if there really was 2.4% oxygen in the carrier gas the column and the MS filament would be long dead. Dehydrogenation does not seem at all likely under GC conditions.

So, is there any evidence besides the plausible reaction with methamphetamine that there really is formaldehyde present ?

Peter

[HW Mueller]

I go with Peter on this, because it is not easy to get an oxidation to stop at the aldehyde. That is a nice hunt to find out what went wrong suddenly. One needs to be very careful not to put too much belief into some working hypotheses.

(Peter, no matter what the mechanism is, the reaction from an alcohol to an aldehyde is an oxidation).

[Peter Apps]

(Peter, no matter what the mechanism is, the reaction from an alcohol to an aldehyde is an oxidation).

Hans, give me a chance, I'm just a zoologist !!

Peter