Abstract: Objective: To establish a sensitive and specific RP-HPLC method for determination pseudoephedrine hydrochloride in human plasma.Methods: Human plasma with internal standard was extracted by methyl t-Butyl ether after being alkalinized.The supernatant was volatilized and then dissolved by 100μl mobile phase.The ZORBAX SB-C18 column（4.6×150mm,5 μm）was used with mobile phase of methanol-aqueous phase（5∶95,0.75% triethylamine and regulate pH to 6.6 by H3PO4）.The flow rate was 1.0 ml·min-1 and the detection wave was 213 nm.Results: The linear range of pseudoephedrine was 0.05～1mg L-1.The relative recovery were within 94.4%～118.2%,the within-day and the between-day RSD were all less than 9.8%.Conclusion: This simple,specific and stable method is suitable for the determination of pseudoephedrine hydrochloride in human plasma.