OBJECTIVE:To establish RP-HPLC combined with solid phase extraction method to determine the plasma concentration of lansoprazole.METHODS:The sample was extracted by solid phase extraction in darkness.RP-HPLC was applied using Venusil XBP-C18(200 mm?4.6 mm,5 ?m) column.The mobile phase consisted of acetonitrile-water(32:68,pH value adjusted to 7.6 with 1% ammonia water) and flow rate was 1.0 mL?min-1.The detection wavelength was set at 284 nm and column temperature was set at room temperature.RESULTS:The linear range of lansoprazole was 10～2 500 ng?mL-1(r=0.999 9) with mean recovery of 100.93%.The RSD of intra-day and inter-day were both less than 10%.CONCLUSION:The method is sensitive,convenient and rapid for the determination of lansoprazole concentration in plasma.