Abstract: The restricted access stationary phase (RAS) are a new type of chromatographic packing material having a hydrophobic interior covered with a hydrophilic barrier. The RAS is used for direct injection in highperformance liquid chromatography for determination of drugs in biological fluids. These stationary phases include internal surface reverse phase, semipermeable surface, shielded hydrophobic phase and mixed functional phase (MFP). A kind of MFP packing material was synthesized from a porous silica gelintroduction of hydrophobic phenyl phase and introduction of hydrophilic diol phase. The MFP of RAS, on which proteins were eluted in the void volume, while the drugs were retained and separated, can be used for direct injection analysis of hydrophilic and hydrophobic drugs in serum and plasma. The recovery of the drugs in human serum was almost 100% with good reproducibility.