AIM: To establish a ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to determination the plasma concentration of clozapine and compare the bioequivalence of a generic clozapine tablet with Clozaril?. METHODS: A randomized, open-label, multiple-dose, steady-state, two-treatment, two-period, crossover study was conducted on Schizophrenia patients who had been receiving a stable dose of clozapine for at least three months under fasting condition. Twenty-four schizophrenia patients were orally administrated with Clozaril tablets or the generic clozapine tablet 100 mg every 12 h for 10 days, then switched to the other formulation for the next 10 d. The concentrations of clozapine in plasma were determined by an estabilished UPLC-MS/MS method. RESULTS： The method was validated by investigating the accuracy and precision for intra and inter-day runs in a linear concentration from 5-2 000 ng/mL. The main pharmacokinetic parameters of test and reference formulation in plasma were shown as follows: Tmax,ss were (1.01-5.02) and (1.00-5.00) h；Cmax,ss were (665.0 ± 279.3) and (679.5 ± 240.3) ng/mL; AUC0-τ were