OBJECTIVE： To develop a method for the concentration determination of olanzapine， risperidone and paliperidone in human plasma. METHODS： After liquid-liquid extraction， using buspirone hydrochloride as internal standard， the concentration of plasma sample was determined by UPLC-MS/MS. The determination was performed on ACQUITY UPLCTM BEH C18 column with mobile phase consisted of methanol-0.01 mol/L ammonium formate solution （gradient elution） at flow rate of 0.2 mL/min. The column temperature was 45 ℃， and sample size was 5 μL. The electrospray ionization source was adopted for positive ion scanning under MRM mode. Ion-pairs for quantitative analysis were as follows： m/z 313.29→256.25 （olanzapine）， m/z 411.42→191.19 （risperidone）， m/z 427.45→207.18 （paliperidone） and m/z 386.43→122.37 （internal standard）. RESULTS： The linear ranges of olanzapine， risperidone and paliperidone were 0.426-108.954， 0.213-54.476， 0.213-54.476 ng/mL， respectively. RSDs of inter-day and intra-day were all lower than 20％. The recoveries of them ranged 83.3％-112.9％， 90.0％-109.8％ and 95.2％-114.9％， respectively. Extraction recoveries ranged 65.5％-95.0％， 73.9％-98.5％ and 73.6％-99.4％， respectively. Both plasma matrix effect and dilute effect didn’t influence the determination of plasma concentration. The plasma concentrations of olanzapine， risperidone and paliperidone in 100 schizophrenia patients were （103.3±73.6），（13.1±13.1）and（23.2±20.0）ng/mL， respectively. CONCLUSIONS： The method is simple， rapid， sensitive and specific. It can be used for the determination of plasma concentration and pharmacodynamic study of olanzapine， risperidone and paliperidone.