Zero air vs. pure nitrogen as ESI source gas for LC-MS/MS.

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

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A strange situation among LC-MS/MS manufacturers has developed. (I will try to avoid using manufacturer's names.)

Some manufacturers are now requiring (or strongly recommending) "zero-air" for ESI source gas, while others are requiring nitrogen for the source gas. This is source gas only, not sweep or collision. The theory I was told was there would be less corona discharge in the source and better sensitivity.

While zero-air should be cheaper to generate than N2 (in theory), nitrogen is still needed for other uses on these mass spectrometers; therefore, it actually increases cost and complexity of supplying 2 (or more) separate gases.

Our laboratory has been using pure N2 as a source gas for years. We recently put a single method head-to-head on the same instrument with N2 versus zero-air as the source gas using identical settings. We saw no difference in any results, but that was for a single method.

Has anyone actually observed where there is a significant benefit to using zero-air over N2 as the source gas? What conditions/compounds/method was this for?

(I would presume that N2 would offer longer gas heater life and less chemical oxidation for some compounds in the source and a theoretical higher fire risk -- but these are both only theories too.)
LC is not in my wheelhouse but I recall our PFAs group running into stability/reproducibility issues trying to hit 1.6-4 ng/L for EPA 533. We ordered a zero air cylinder for testing but ended up installing a large module with three individual gas filters for each LC. Still ended up moving sample volume up from 125 to 250 mL to get the blanks to reliably pass.

Not sure if those filters were for the source gas or not.
Thank you.

Surprised that the manufacturer would recommend a blanket instrument configuration change for one class of compounds, which I assume is in negative mode for PFAS.

I am wondering if "zero-air" is that much better, because we didn't see any noticeable difference. Also, other manufacturers are still requiring pure N2 for their instruments and still perform PFAS.
bcd_GCLCMSMS wrote:
Thank you.

Surprised that the manufacturer would recommend a blanket instrument configuration change for one class of compounds, which I assume is in negative mode for PFAS.

I am wondering if "zero-air" is that much better, because we didn't see any noticeable difference. Also, other manufacturers are still requiring pure N2 for their instruments and still perform PFAS.


Some also recommend Argon as the collision gas while others say stay away from it.

Also we had one that said Nitrogen from the gas generator was ok for collision (99% pure) while another said we had to use UHP from a cylinder(99.995% or better).
The past is there to guide us into the future, not to dwell in.
Glad to see this topic as I had the same question and did not find a good answer. I would like to know pros and cons of nitrogen vs zero air for desolvation and nitrogen vs argon for collision.

Another question is: how come zero air desolvation with a flamabel solvent like methanol and high voltage is not a fire hazard? Our manual states that it is important to have a working nitrogen flow that removes oxygen to avoid fire hazards when source is in operate mode for ESI.
Excellent points and questions!

I have often wondered about the flammability aspect in ESI sources, since the gas is being nebulized AND heated well above its flash point. I have never seen a fire in a source, but then again, I have, until this past year, used nitrogen for all the gases, except the collision.

For collision I default to the manufacturer's recommendation. Also, the collision gas flow is so low, the cost difference of Ar vs. N2 is not an issue. (There are minor differences in collision energy voltage needed between nitrogen and argon to achieve optimum fragmentation for each, but I have never found a method that would only work with one and not the other.)
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