Abstract: OBJECTIVE To establish a rapid and sensitive HPLC-MS method for simultaneous quantitative determination of carbamazepine(CBZ) and phenytoin(PT) in human plasma. METHODS Plasma samples were precipitated with acetonitrile and determined by HPLC-MS using lansoprazole as an internal standard. The separation was carried out on a Diamonsil C₁₈ column(2.1 mm×150 mm, 5 μm) with a mobile phase of methanol-water(including 0.1% formic acid)(0.20∶0.10) and with a flow rate of 0.3 mL·min^-1. ESI was performed in the MRM positive mode using target ions at m/z 237.0/194.0(CBZ), 253.2/182.0(PT), and 392.0/188.2(lansoprazole), respectively. RESULTS The RSD of average recovery rate for CBZ on three levels of concentration of low(66.08 ng·mL^-1), medium (660.8 ng·mL^-1) and high (16 120 ng·mL^-1), were <15%. The calibration curves of CBZ was obtained in the range of 40.3-20 150.0 ng·mL^-1(r=0.993 7) with good linearity. The low limit of quantitation was 40.3 ng·mL^-1. Meanwhile, the RSD of average recovery rate for CBZ on three levels of concentration of low (133.5 ng·mL^-1), medium (1 335.00 ng·mL^-1) and high (32 040.00 ng·mL^-1), were also <15%. The calibration curves for PT was obtained in the range of 80.1-40 050.0 ng·mL^-1(r=0.997 6) with good linearity. The low limit of quantitation was 80.1 ng·mL^-1. CONCLUSION The method provides a sensitive, accurate, precise and reliable analytical procedure for the therapeutic drug monitoring of CBZ and PT simultaneously in clinic and phamacokinetic studies.