INCURRED SAMPLE STABILITY OF AMLODIPINE BESYLATE AND VALSARTAN IN HEALTHY HUMAN PLASMA BY LIQUID CHROMATOGRAPHY TANDEM MASS SPECTROMETRY

Abstract

This study aimed to evaluate incurred sample stability of amlodipine besylate and valsartan in plasma after administration of fixed dose combination tablet of amlodipine besylate and valsartan using Liquid Chromatography – Tandem Mass Spectrometry. Blood were collected from six healthy subjects until 72 hours after drug administration. Plasma samples were analyzed using LC-MS/MS with Waters Acquity TM BEH C18 column (100.0 mm × 2.1 mm, 1.7 µm). Mass detection was performed by ESI positive in MRM mode. Amlodipine besylate (AML), Valsartan (VAL), and Irbesartan (IRB) were detected at m/z 409.16 > 238.06; 436.22 > 291.15; and 429.22 > 207.1; respectively. Sample was extracted using ethyl acetate. The mobile phase consisted of 0.1% formic acid and acetonitrile with gradient elution, the flow rate was 0.2 mL/min. The obtained samples were reanalyzed until 30 days. The mean values of Cmax, tmax and AUC0-t for amlodipine besylate were 5.68 ng/mL, 5.83 h and 149.2 h.ng/mL respectively, while the mean values of Cmax, tmax, and AUC0-t for valsartan were 4172.44 ng/mL, 4.17 h, and 31952.45 h.ng/mL respectively. The results of incurred sample stability in plasma samples from six healthy subjects who were administered 10 mg of AML and 160 mg of VAL stored for 30 days were ranged -21.01 until 17.48% for AML and -12.98 until 14.67% for VAL. The incurred sample stability of AML and VAL in human plasma was stable until 30 days after drug administration, with more than 67% incurred samples had %diff value not more than ± 20%.