Abstract: UPLC-TOF/MSE was applied to the screen-testing of 150 drugs and toxic compounds in human whole blood. The human whole blood sample was prepared by liquid-liquid extraction, then separated on ACQUITY UPLC HSS C18 column. Mixtures of 5 mmol·L-1 ammonium formate solution (pH 3.0) and 1% (φ) formic acid-acetonitrile solution mixed in different ratios were used as mobile phase in gradient elution. Modes of positive electric spray ionization and full-scanning were adopted in MS. Detection limits (3S/N) of the 150 drugs and toxic compounds found were in the range of 0.2-25 μg·L-1. Matrix effects for 67 compounds were found in the range of 17.4% to 126%, and values of recovery of liquid-liquid extraction were ranged from 29.7% to 114%.