Hypertension therapy is one of the ways for reducing the cardiovascular diseases, such as pharmacology therapy using amlodipine besylate and valsartan. Antihypertensive agents are drugs for serious condition that need bioequivalence test. Bioequivalence testing for generic prodrug development is carried out in long period of time, so it is necessary that the stability of amlodipine besylate and valsartan to be known by analyzing the incurred sample stability. This study aimed to analyze the in vivo stability of amlodipine besylate and valsartan on subjects’ plasma samples on days 7, 14 and 28 in the C_max phase and elimination phase. Amlodipine besylate and valsartan analysis were performed on 6 healthy subjects administered a fixed dose combination of amlodipine besylate and valsartan tablets that contain amlodipine besylate 10 mg and valsartan 160 mg. The subjects’ blood was collected in 18 points at several times up to 72 hours. The chromatographic conditions used was the Acquity® UPLC BEH C₁₈ column (2.1 × 100 mm × 1.7 µm); column temperature was 45^oC; mobile phase consist of 0.1% acetonitrile and formic acid in water with gradient condition; flow rate 0.2 mL/minute with total run time of 6 minutes. Mass detection was performed using Waters Xevo TQD equipped with an electrospray ionization (ESI) source in positive mode with MRM mode. The pharmacokinetic profile in human plasma results were; C_max 4.86 – 6.56 ng/mL; t_max 5.33 hours for amlodipine besylate and C_max 3570.00 – 4553.34 ng/mL; t_max 4.17 hours for valsartan. The %diff values of amlodipine besylate and valsartan incurred sample stability until day 28 on 6 subjects not more than 20%, which fulfilled the acceptance criteria of validation method based on EMEA Bioanalytical Guideline 2011.