Chromatography Forum

Crude peptide synthesis products contain hydrophobic components that foul a column by binding irreversibly, or else require frequent column regeneration. To prevent fouling using preliminary solid phase extraction (no guard column), would dissolving the sample in 60% MeCN (enough organic to prevent desired peptide binding) and passing through a RP solid-phase extraction bed remove these hydrophobic impurities as effectively as if the sample were applied to a SPE bed in low organic, (where most material, including desired peptide will bind) and eluted in 60% MeCN?

It should work but my guess is that it will not do as good a job as the "retain-then-elute" approach. The trick is to find the lowest % organic that will assure quantitative desorption (or, more accurately, non-sorption) of your product.

Try it both ways and see what happens.