Stability of Reference Masses in water or methanol

Hi everyone, 

I am using a 6546 LC-QTOF and have recently traced back some fairly significant ion suppression problems to the acetonitrile used to prepare my reference mass mix. It seems to be a problem with multiple lots of Fisher Optima LC/MS grade acetonitrile. I am in the process of purchasing similar grade acetonitrile from different suppliers (including Agilent), but if this does not correct the problem, I do know that using water or methanol to prepare the mix instead would alleviate some of the suppression.  

We are using 4 reference masses (two in positive mode, two in negative mode): Purine, HP-0321, Ammonium Trifluoroacetate, HP-0285

Each of these come stored in acetonitrile or acetonitrile/water. 

My question is whether anyone is preparing their reference mass mix in water or methanol? Or, if I choose to prepare it in water or methanol, does anyone know if that would impact the solubility or stability of the reference mass mix? Hoping I can benefit from someone else's experience here. 

Thanks very much, 


  • Hi, I don't think it is a fault of the purity of the solvent. This is normal when using acetonitrile.
    If you are using an iso pump to dose your reference masses, increase the flow rate, as the gradient rises.
    Another option is to change the mobile phase solvent to methanol.
    You may also consider preparing a higher concentration of reference masses, for this specific analysis. 

    In the agilent note you can find: 
    "The abundances of the reference mass compounds change during an HPLC gradient, with lesser abundances occurring at higher organic compositions. This is especially true when using acetonitrile as the organic component. Make sure the abundances are high enough during the entire gradient."

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