A sensitive and accurate LC/MS method for the determination of elbasvir (ELB) and grazoprevir (GZP) in human plasma was established using daclatasvir (DCT) as an internal standard. The analytes were separated on a Waters Spherisorb phenyl column (150 mm x 4.6 mm ID, 5 µm particle size) maintained at 40°C ± 2°C. Gradient elution, at a flow rate of 0.8 mL min-1, was used. The mobile phase consists of 90% of acetonitrile mixed to 10% of a 5 mM ammonium formate buffer (+ 0.1% v/v of trimethylamine, pH was adjusted to 3.2 by formic acid) as phase A and 10% of acetonitrile mixed to 90% of the same buffer as phase B. Liquid-liquid extraction with ethyl acetate solvent was used to recuperate compounds from plasma. The method was validated over a concentration range of 2 and 100 ng/mL for GZP and between 1 and 50 ng/mL for ELB. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD) < 15%, and the accuracy values ranged from 94.2% to 107.8%. The robustness of the method was established using a two-level full factorial design.