Objective To develop a rapid LC-MS/MS method to determinate the concentration of irbesartan and amlodipine in human plasma. MethodsSamples were pre-treated using a protein precipitation method and separated by ACQUITY UPLC BEH C_(18)(2.1mmx50 mm, 1.7μm) column in gradient elution model with a mobile phase of acetonitrile(B)-0.1%formic acid in water(A) during 3 min. The column temperature was 40°Cand the flow rate was 0.40m L·min∼(-1). Detection of those two analytes was achived in pos. ion ESI in MRM mode. The MS/MS ion transitions monitored were m/z429.2→m/z 195.1(irbesartan), m/z 409.3→m/z 238.1(amlodipine), m/z 433.2→m/z 195.1 (irbesartan-d4) and m/z 413.3→m/z 238.1(amlodipine-d4). The specificity, standard curves and lower limit of quantitation (LLOQ), precision, matrix effect, recovery and stability were investigated. Results For irbesartan, the linearity range was 10-5000 ng·m L∼(-1)and the standard curve was Y=7.03x10∼(-4)x+7.35x10∼(-4)(r=0.998). The intra-and inter-precision were 1.2%-9.4%, while the relative deviation was-6.1%-4.0%. The matrix effect normalized by internal standard for low middle high QCs was 0.4%-6.6%, and the recovery was 102.0%-105.2%. For amlodipine, the linearity range was0.05-10 ng·m L∼(-1)and the standard curve was Y=4.86x10∼(-2)x+6.66x10∼(-4)(r=0.999). The intra-and inter-precision were 1.1%-10.1%, while the relative deviation was-10.0%-8.3%. The matrix effect normalized by internal standard for low middle high QCs was 0.7%-11.6%, and the recovery was 98.4%-106.6%. Both of those two analytes'stability were good. Conclusion This LC-MS/MS method was simple as well as sensitive, could be used for pharmacokinetics and bioequivalence studies.