OBJECTIVE： To develop a method for simultaneous determination of carbamazepine， venlafaxine， rosiglitazone and nifedipine in human plasma. METHODS： UPLC-MS/MS method was adopted to determine plasma sample after precipitated with methanol （containing 0.1％ formic acid） using pioglitazone hydrochloride as internal standard. The determination was performed on Waters ACQUITY UPLC HSS C18 column with mobile phase consisted of aqueous solution containing 0.01％ formic acid-methanol containing 0.01％ formic acid （gradient elution） at the flow rate of 0.3 mL/min. The column temperature was 50 ℃， and sample size was 5 μL. ESI was used for positive ion scanning by multi reaction monitoring mode. The ion pairs for quantitative analysis were m/z 237.00 to 194.05 （carbamazepine）， m/z 278.20 to 58.10 （venlafaxine）， m/z 358.08 to 135.04 （rosiglitazone）， m/z 347.15 to 315.17 （nifedipine）， m/z 357.09 to 134.06 （internal standard）. RESULTS： The liner ranges of carbamazepine， venlafaxine hydrochloride， rosiglitazone hydrochloride and nifedipine were 2.00-2 000.00 （r＝0.995 9，n＝5）， 2.12-2 120.00（r＝0.990 5， n＝5）， 2.00-2 000.00（r＝0.991 5， n＝5） and 2.04-1 020.00（r＝0.991 0，n＝5） ng/mL； the minimum detection limits were 0.200， 0.106， 0.100， 1.020 ng/mL， respectively.  RSDs of inter-day and intra-day were less than 15％. The absolute values of RE were less than 15％.  The extraction recoveries were 65.66％-96.36％（RSD％＜15％，n＝5）， and matrix effects ranged 80.99％-114.33％. The plasma concentrations of carbamazepine in 2 epileptic patients were （1 500.41±169.11）， （1 159.01±59.24） ng/mL（RSD were 11.27％， 5.60％，n＝3）. The plasma concentrations of nifedipine in 2 hypertensive patients were （14.68±1.92），（21.18±3.59）ng/mL（RSD were 16.98％， 13.10％，n＝3）. CONCLUSIONS： The method is simple， specific， sensitive， accurate and suitable for the monitoring of plasma concentration and pharmacodynamic study of above drugs.