Abstract: Using the new technology of the sample pre-treatment SPE and AMDIS to establish a simple and fast method to extract and analyse common hypnoticsedative drugs (including acidity, alkalescence and litmusless). Comparing OasisHLB cartridge、C₁₈ and C₂ three categorys SPE column to extract simultaneity 13 sedative drugs and 2 internal standards in the blood, and the effect on covery by different eluant, different eluant quantities different PBS quantities. The covery of Oasis HLB cartridge were over 83% for the most of drugs;chloroform were most effectly eluant by 3 mL and 2 mL PBS were optimal quantities. The method had the characteristic of simple and quick operation,high recovery, good repeatability and clean extract, It can be applied to the cases of determinating hypnotic sedative drugs in the blood.