I'm using SPE to clean up plasma for trace drug analysis. I'm getting inconsistent extraction results. My internal standard will sometimes extract well and other times come out very low, even though cartidges were treated in exactly the same fashion. What gives?

Give us a few more details on the procedure. It is possible that you use an elution solvent that just does not have enough strength. It is possible that the timeframe of the elution is drastically different. It is possible that your SPE device dries before loading of the sample. Other things are possible as well. Is the internal standard affected by the pH of the sample?

Check with your supplier for trace metal analysis between lots, or ask for help. We found at the USDA that our SPE recoveries were dependent on low trace metals. We were losing key analytes due to their affinities for certain inorganic cations. Also, if a particular lot of SPE cartridge works, ask your supplier to reserve that lot for you. Also, make sure you are conditioning the cartridge properly, as well as keeping flowrate the same between samples. Hope this helps.