C18/SCX SPME was used to measure free concentrations of ionized pharmaceuticals.
Cfree can be used to calculate binding affinities to bovine and human serum albumin.
Fouling effects were observed and quantified but had limited effects on binding affinities.
Kinetic and equilibrium SPME resulted in similar calculated binding affinities.
C18/SCX SPME application allows sensitive determination of protein binding of cations.