An 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 µ) column. The developed method was extended to bio-equivalence studies, in which pharmacokinetic parameters like Concentration time profiles, Cmax, AUC0 − t, AUC0−α, Tmax, T1/2, Kel, for lercanidipine was estimated. Statistical methods are used to analyze the log-transformed pharmacokinetic parameters AUC0 − t, AUC0−α and Cmax for bioequivalence of each of these parameters. Statistical analysis will be performed using WinNonlin Software, Matrix effect was assessed by post-column infusion, post-extraction spiking and standard-line slope methods. The analyte and 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 that both studies of lercanidipine under similar conditions and there is no any in vivo conversion of enantiomers. The presences of the R-enantiomer and S-lercanidipine concentration were similar then the presence of R-enantiomer spares the S-lercanidipine (eutomer) from first-pass metabolism and decision to develop the recemic form of lercanidipine.