I stopped using C18 for concentration and cleaning, prefering SCX. But, in this case wouldn't you just use 0.1% TFA to load as an ion pair and then elute with a step gradient of ACN? TBH, I'd use SCX instead cause it SHOULD be ignorant of the hydrophilicity/phobicity of the peptides.

Yep and we have a good protocol for SCX- but, I need to further reduce the presence of fully hydrophobic peptides, so it might not be the way to go here. If the C18 is a complete fail, I will probably try SCX anyway 😅