How does protein binding affect my extraction? (Pretreatment series)

Protein binding is a major concern with proteinaceous samples.  Protein binding occupies analytes’ interactive functional groups and takes away analytes’ ability to interact with the sorbent. 

Protein bound analytes are also likely to get carried through a cartridge with proteins that are too large to penetrate sorbent pores or have unspecific binding to the SPE sorbent.

All of these factors discussed lead to analyte loss and method inconsistency.