Abstract: OBJECTIVE To develop an HPLC method for the quantitative determination of ziprasidne hydrochloride in plasma. METHODS The residues were analyzed with a RP-HPLC used Kromasil C₁₈ column(4.6 mm×250 mm, 5 μm) with the mobile phase consisted of methanol-acetonitrile-40 mmol·L^-1 ammonium acetate (With acetic acid adjust to pH 3.5±0.1) (100∶100∶155). The flow rate was 1.0 mL·min^-1, and carbamazepine was used as internal standard. The detection wavelength was set at 254 nm. RESULTS Linear regression analysis was made by ziprasidne hydrochloride plasma concentration(C) and the peak area ratio (Y) of ziprasidne hydrochloride to internal standard (carbamazepine), the regression equation was C=213Y-85.5(r=0.996 2). The results showed that ziprasidne has a good linear relationship in the range of 20.0-1200 μg·L^-1. The average recovery of ziprasidne hydrochloride was 97.38%. CONCLUSION The method provides a simple and accurate way for clinical monitoring of ziprasidne hydrochloride in plasma.