Abstract: OBJECTIVE To develop the method for concentration determination of carbamazepine, lamotrigine, clonazepam, diazepam and oxazepam in human plasma. METHODS UPLC-MS/MS was adopted to analyze plasma with protein precipitated by methanol and sulfamethlazole(SMZ) was used as internal standard. Plasma samples were separated on Waters ACQUITY UPLC HSS PFP(2.1mm×100 mm,1.8 μm) column with aqueous solution(0.1% formic acid 5 mmol·L^-1 ammonium acetate buffer)-0.1% formic acid method(0-5 min, 35∶65→10∶90) as mobile phase, and at a flow rate of 0.2 mL·min^-1. The protonated ion of samples was detected in positive ionization by multiple reaction monitoring(MRM) mode. The target compounds carbamazepine, lamotrigine, clonazepam, diazepam, oxazepam and SMZ were quantified with m/z 237.0→194.06, m/z 255.98→144.95, m/z 316.01→270.0, m/z 285.04→193.07, m/z 287.02→241 and m/z 253.96→91.97, respectively. RESULTS The liner calibration curve of carbamazepine, lamotrigine, clonazepam, diazepam and oxazepam were obtained in the concentration range of 2.4-600 ng·mL^-1(r=0.999 7), 2.52-630 ng·mL^-1(r=0.992 0), 2.08-520 ng·mL^-1(r=0.997 9), 2.28-570 ng·mL^-1 (r=0.998 2) and 8.0-800 ng·mL^-1(r=0.999 2), respectively. The lowest detection limit were 0.24 ng·mL^-1, 0.63 ng·mL^-1, 0.52 ng·mL^-1, 0.57 ng·mL^-1 and 3.2 ng·mL^-1, respectively. The RSD of inter-day and intra-day were less than 15%. The relative recovery was more than 70%, and the RSD was less than 15%. CONCLUSION The method is accurate, sensitive and suitable for blood concentration monitoring and pharmacokinetic study of carbamazepine, lamotrigine, clonazepam, diazepam and oxazepam.