This research developed and validated a highly sensitive and selective UPLC–MS/MS approach using a triple quadrupole mass spectrometer for quantifying favipiravir. Moreover, we introduced a study evaluating bioequivalence using two drugs, Favibrivix and Avigan, containing favipiravir. Lean Six Sigma verified the capacity and performance of the process. Protein precipitation extraction was utilized to extract favipiravir from the collected human matrices. We used an Acquity UPLCr BEH HILIC column and valproic acid as an internal standard. Furthermore, we conducted the procedure using an isocratic elution comprising acetonitrile and 0.005% ammonia in water (75:25, v/v), a flow rate of 0.25 ml/min, a temperature controlled at 10°C and an injection volume of 1.0 μl. Our UPLC–MS/MS process has a broad range (50–10,000 ng/ml) with a determination coefficient of 0.9980. We validated the method in line with the US Food and Drug Administration. The findings revealed that the test, Favibrivix 200 mg/tablet, and the reference, Avigan® 200 mg/tablet, were statistically bioequivalent in healthy Egyptian participants.