Lercanidipine is the new generation of antihypertensive calcium channel blocker of dihydropyridine class. As the drugs uses in serious condition, these drugs need to be bioequivalence test, so it’s necessary to develop bioanalytical methods that are reliable, fast, and has high sensitivity. Therefore, the aim of this study was to obtain the optimum method and validated to analyze lercanidipine in plasma using Ultra-High Performance Liquid Chromatography tandem Mass Spectrometry (UPLC-MS/MS). Chromatographic separation was performed by a Waters Acquity^TM UPLC C18 1,7 µm (2,1 x 100 mm) column with a mobile phase a mixture of 0,1% formic acid - methanol (20:80 v/v) with isocratic elution, the column temperature 30 °C, flow rate was 0,2 mL/min and used amlodipine as internal standard. Mass detection was performed on Waters Xevo TQD equipped with an electrospray ionization (ESI) source at positive ion mode in the Multiple Reaction Monitoring mode. Lercanidipine was detected at m/z 612,11 > 280,27 and amlodipine was detected at m/z 409,1 > 238,15. The optimal sample preparation was carried out by liquid-liquid extraction method using 5 mL of a mixture of n-hexane - ethyl acetate (50:50 v/v) as extracting and reconstituted with 100 µL of mobile phase. This method was linear at concentration range of 0,025 to 10 ng/mL with r≥0.9986. This method fulfill the acceptance criteria for accuracy and precision, selectivity, carry over, stability, dilution integrity and matrix effects based on Guideline on Bioanalytical Method Validation by the European Medicines Agency in 2011.