Treating column with EDTA prior to use on LC/QTOF

UPDATE: 

Thank you for the input! I figured I'd share what we did in case someone else has this issue. 

Not wanting to use the EDTA disodium salt and potentially contaminate the system with sodium ions, I went with the trace metals 99.995% pure EDTA from sigma (431788-25G) . Due to the poor solubility of the free acid I titrated to pH 8 with MS-grade ammonium hydroxide to generate the diammonium EDTA at ~40 mM. (Definitely worth doing in a hood haha) 

I first ran the Agilent phosphoric acid passivation procedure recommended for using the InfinityLab deactivator without the column installed. Then I flushed overnight with the diammonium EDTA with the column attached. (ALL OF THIS WAS TO WASTE. NOT THE MS) 

This did help slightly compared with earlier tests but not nearly as well as just shooting large amounts of our protein... 

I will add that it had the side effect of making our peptide mapping look excellent (as to be expected) 

I'll be trying the InfinityLab deactivator (medronic acid) next.

Appreciate the update! Proteins binding to active sites is of course common for SEC- past experience makes me blame the column frit, but proteins can indeed bind to silica-based SEC columns.

Sufficient cosolvent/salt (typically potassium or sodium phosphate in LC-UV) suffices to minimize adsorption due to negatively charged silanols. Particularly hydrophobic proteins may then stick to the stationary phase (commonly a propyl-diol or similar), though this is commonly more an issue with high concentrations of salt in the mobile phase. 

For Native MS applications, more often than the mobile phase is 20-50 mM ammonium acetate unadjusted; definitely not sufficient salt for particularly basic proteins. Peak tailing and/or "non-ideal" SEC behavior (elution times not corresponding to hydrodynamic radius) would indicate that was the case. In these instances, 100 mM might be required; this could potentially kill signal but there are workarounds...

Either way, if priming helps (I'd say upwards of 20-50 µg on a 2.1x150 mm ID), then this is a good workaround. However, bear in mind that storing the column in a sufficient organic to act as a bacteriostat (e.g. 10-20% methanol) will likely strip the active sites and require priming again. 

Appreciate the update! Proteins binding to active sites is of course common for SEC- past experience makes me blame the column frit, but proteins can indeed bind to silica-based SEC columns.

Sufficient cosolvent/salt (typically potassium or sodium phosphate in LC-UV) suffices to minimize adsorption due to negatively charged silanols. Particularly hydrophobic proteins may then stick to the stationary phase (commonly a propyl-diol or similar), though this is commonly more an issue with high concentrations of salt in the mobile phase. 

For Native MS applications, more often than the mobile phase is 20-50 mM ammonium acetate unadjusted; definitely not sufficient salt for particularly basic proteins. Peak tailing and/or "non-ideal" SEC behavior (elution times not corresponding to hydrodynamic radius) would indicate that was the case. In these instances, 100 mM might be required; this could potentially kill signal but there are workarounds...

Either way, if priming helps (I'd say upwards of 20-50 µg on a 2.1x150 mm ID), then this is a good workaround. However, bear in mind that storing the column in a sufficient organic to act as a bacteriostat (e.g. 10-20% methanol) will likely strip the active sites and require priming again.