Solid phase extraction may employ hydrophobic, polar, ionic or a combination of mechanisms. Frequently, an internal standard is added in order to provide quantifiable results. Sample application can be optimized by removing particulates via centrifugation or filtration. Viscous matrices may also be diluted with water or buffers (ensure that sample is at the correct pH for the desired retention mechanism being employed).

On ion exchange sorbents, sample analytes must be oppositely charged from the sorbent functional phase. Negatively charged (-) anionic compounds are drawn to positively charged (+) anion exchange sorbents. Positively charged (+) cationic compounds bind to negatively charged (-) cation exchange sorbents. During sample application, the analyte binds by displacing a counter ion on the sorbent. The sample is applied to the sorbent bed at a rate of 1 mL / minute. A momentary increase in vacuum may be needed to initiate flow.