Does ammonium fluoride assist ionisation? (and how?)

Hi I recently read a report in which 1mM ammonium fluoride was added to the LC-MS mobile phase to increase sensitivity/ionisation. Can anyone verify this is effective for ESI positive mode analysis of drugs? Can you point me to a reference that describes how this works (if it does) 



  • Hi


    There is this Agilent document:


    "Improved Analysis of Trace Hormones in

    Drinking Water by LC/MS/MS (EPA 539)

    using the Agilent 6460 Triple Quadrupole



    In there the 1mM ammonium fluoride method is described.



  • Ok thanks, so it’s not much use if M+H is your main pseudomolecular ion then I take it…

    When you say fluoride will ‘suppress sodium’, I assume you mean the fluoride ions co-ordinate in solution with sodium ions better than say, chloride or non-ionised drug molecules. Effectively mopping up the sodium- it that the theory here?



  • Hi Peter, 


    Using ammonium fluoride in your mobile phase will introduce free ammonium ions to create the ammonium adduct of your compounds. If you're detecting the ammonium adduct, having free ammonium ions is a prerequisite to good ionization.


    It is the same concept as using ammonium formate, but you get the added benefit of the free fluoride ions working to suppress free sodium ions. Every molecule of your compound that forms the sodium adduct won't be able to form the ammonium adduct! Le Chatelier's principle still applies. 




  • You've got it, Peter. If you're only detecting M+H then ammonium fluoride wouldn't normally be used.


    You could potentially gain some benefit if you were observing a lot of sodiated species, but you may introduce the potential for competitive reaction to create the ammonium adduct of your compound. If someone was struggling with excess sodium ions I would guide them to reduce exposure to glass wherever possible (PTFE mobile phase bottles, SS inlet frits, poly propylene vials, etc.). 


    If you're looking at a broad panel of drugs and are detecting some ammonium adducts I would consider adding it to your aqueous mobile phase along with your acid as a substitute for ammonium formate. A quick experiment comparing the two would show the winner in your specific application. 

  • Addition of NH4F would changed process of ionisation, but 1mM mentioned in the app note seems to be a lot. I am using 0,2mM NH4F, in Santa Clara are using even less. Addition of formic acid or acetic acid (about 20-50uL into 1L) would stabilise retention times. Using of pure NH4F usually reulted in cloged column, addition of acid really helped.

    Ammonium fluoride would help you with a response of many problematic analytes (phenols, phenoxy acids), it is helping in both, positive and negative ESI. It is not good for every compound, but it is very good for majority of small molecule analytes I ever tested (pesticides, pharmaceuticals, mycotoxins, alkaloids, lipids, polyphenols...).   

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