30 mM Sulfuric Acid & LC-MS?

[Arne]

Hello all,

I have been approached by somebody in another lab with the request to identify peaks in their HPLC run by LC-MS. However, their mobile phase contains 30 mM sulfuric acid (pH 1.5)....

I am not keen on having that mobile phase go through our ESI source. and cause corrosion, especially at elevated temperature. At the same time, it is critical to identify said peaks.

Do you have any suggestions on how to compatibilize this HPLC method with ESI (or APCI)?

I am considering installing a 1:10 or so splitter post-column and then mixing with enough ammonium acetate buffer before the source to neutralize the acid. I will not be sensitivity limited at all. Does that sound like a viable plan?

Should I expect long term contamination with sulfuric acid-related ions? I had this happen with phosphoric acid before.

Thank you very much in advance!

Arne

[Hollow]

maybe not as you still have the non-volatile sulfate in your eluent (similar to phosphates)

Maybe it is possible to replace the sulfuric acid with some volatile acid like TFA or Difluoroacetic acid (less ionsupression), or even a (higher concentrated) formic acid can do the trick?
Of course, the other lab should also redo the chromatography with the new modifier, to recheck the peak order.

Otherwise, maybe de-sulfating fractionated peaks by SPE would be an option for this "one time task". (fractionate, dilute with water, load on SPE, elute with sulfate free solvent and reanalyze with a generic, MS-friendly method or direct MS infusion)
A 2D-LC setup for this online SPE task would be nice.

[lmh]

As a matter of interest, sulphuric acid is indeed hideously corrosive to an LC-MS, even at muuuuuch lower concentrations. But it gives really nice sulphate adducts of the analytes. Don't ask how I know...

[Arne]

Thank you for the replies guys! It turns out the customer is not interested in the region of the chromatogram in which sulfuric acid is used as a modifier. I will jsut use the switching valve and divert the flow away from the MS during the first part of the analysis.

I'll let you know how it went....

[Arne]

Despite using a divert valve there was a serious signal for HSO4-, H3S2O8-, and methyl bisulfate. Flushing the system with water cleared it out easily.

Overall, it was worth doing the analyses.

[Alp]

I assume you are required to run the same HPLC conditions in order keep the elution order and elution time the same and to put m/z to those specific peaks seen in the HPLC runs.

It can take up to several minutes to flush out all the H2SO4 from the column, as you have probably discovered.

If it were me trying this, I would look into developing a similar chromatographic method but with use of acetic acid or formic acid.