Improved and Reliable Liquid Chromatography/Tandem Mass Spectrometry (LC-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 Lercanidipine in human plasma by using LC-MS/MS with symmetry C18 (75 x 4.6 mm, 3.5 mu) column. The developed method was extended to bio-equivalence studies in which pharmacokinetic parameters (PK) like concentration time profiles, Cmax, AUC(0-t), AUC(0-alpha), T-max, T-1/2, Kel, for lercanidipine were estimated. Statistical methods were used to analyze the log- transformed pharmacokinetic parameters AUC(0-t), AUC(0-alpha) and C-max for bioequivalence of each of these parameters. Statistical analysis was performed using WinNonlin software. The matrix effect was evaluated using standard-line slope, post-column infusion and post-extraction spiking techniques. IS's mean extraction recovery was >94%. Five quality controls had an average accuracy (% CV) of 5.8% between batches and among batches. The results obtained for recemic and enantiomers lercanidipine were under the acceptance criteria. It shows both studies of lercanidipine under similar conditions and there is no in vivo conversion of enantiomers. When the concentrations of theR-enantiomer and S-lercanidipine were comparable, the R- enantiomer's presence protected the ester of S-lercanidipine from first-pass metabolism and the choice to produce the recemic version of the drug.