Abstract: The blood sample was extracted with acetonitrile, and then centrifugated for 10 min at the speed of 8 000 r·min^-1. The supernatant was filtered on 0.22 μm organic filtration membrane. UHPLC-MS/MS was applied to the determination of 20 common drugs in the filtrate. ACQUITY UPLC HSS C₁₈ chromatographic column was used as stationary phase, and the mixture of acetonitrile and 5 mmol·L^-1 ammonium formate solution (pH 3.0) mixed in different ratios was used as mobile phase in gradient elution. ESI⁺ and multi-reactions monitor mode were adopted in MS/MS. Linear relationships between values of peak area and mass concentration of the 20 drugs were kept in the same range of 10.0-100 μg·L^-1, with detection limits (3S/N) in the range of 0.10-5.00 μg·L^-1. On the base of blank sample, test for recovery was made by standard addition method; values of recovery found were in the range of 42.3%-113%, with intra-day RSDs (n=5) and inter-day RSDs (n=3) of determined values in the ranges of 0.050%-15% and 2.1%-15%, respectively.