The matrix may contain various levels of compounds which interfere with the extraction. If salts in the sample cause inconsistent retention, dilute the sample with water. A high level of lipids in the sample can reduce the retention capacity of the sorbent for the isolate. This may require the use of a larger sorbent bed. Adjust the sample pH to suppress ionisation of the isolate.
Neutral compounds retain better on non-polar sorbents than ionised compounds.
In biological samples, the isolate may be protein-bound. Break this interaction by adjusting the pH, adding denaturing compounds, or precipitating the protein. Ensure that the cartridge is being properly conditioned and that flow rates during sample application and elution steps are not too high.