An improved and reliable ultra-performance liquid chromatography/tandem mass spectrometry(UPLC–MS/MS) method has been developed and validated for the determination of lercanidipine in human plasma. Plasma samples with lercanidipine-d3 as an internal standard(IS) were prepared by solid phase extraction on Phenomenex Strata-X cartridges using 100 μL of human plasma. Chromatographic analysis was performed on UPLC BEH C_(18)(50 mm*2.1 mm, 1.7μm) column under isocratic conditions. Linear calibration curves were obtained over a wide dynamic concentration range of 0.010–20.0 ng/mL. Matrix effect was assessed by post-column infusion, post-extraction spiking and standard-line slope methods.The mean extraction recovery was >94% for the analyte and IS. Inter-batch and intra-batch precision(%CV) across five quality controls was <5.8%. Bioequivalence study was performed with 36 healthy subjects after oral administration of 10 mg of lercanidipine and the assay reproducibility was evaluated by reanalysis of 133 incurred samples. An improved and reliable ultra-performance liquid chromatography / tandem mass spectrometry (UPLC-MS / MS) method has been developed and validated for the determination of lercanidipine in human plasma. Plasma samples with lercanidipine-d3 as an internal standard (IS) were prepared by solid phase extraction on a Phenomenex Strata-X cartridges using 100 μL of human plasma. Chromatographic analysis was performed on UPLC BEH C_ (18) (50 mm * 2.1 mm, 1.7 μm) The wide dynamic concentration range of 0.010-20.0 ng / mL. Matrix effect was assessed by post-column infusion, post-extraction spiking and standard-line slope methods. The mean extraction recovery was> 94% for the analyze and IS. Inter-batch and intra-batch precision (% CV) across five quality controls was <5.8%. Bioequivalence study was performed with 36 healthy subjects after oral administration of 10 mg of lercanidipine and the assay reproducibility was evaluated by reanalysis of 133 incurred samples.