We have developed a novel polymer-based restricted access material (RAM) column for small molecule analysis. This column operates as a reversed-phase column, but it has size-exclusion and normal-phase properties. It retains very well both polar and non-polar molecules under MW 1,000 even in the presence of proteins. It is especially useful in minimizing sample preparation for small molecule analysis in biological fluids, e.g., serum, plasma, urine, etc. This column is operational in pH range of 3 � 12, temperature range of 20 � 60 deg.C, and pressure of up to 150 bar. The column generates sharp peaks even with low salt concentration and without ion pairing reagent.

We applied ODP2 HP column for drug molecule analysis in BSA and control serum by column-switching experiment in a LCMS system. We obtained good recovery rate of 88 to 112% with a wide variety of small molecules.