Fully validated UPLC–MS/MS method for quantifying Favipiravir in human plasma boosted lean six sigma: An application for a bioequivalence study

Abstract

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.

Insights into the sustainability of liquid chromatographic methods for favipiravir bioanalysis: a comparative study

“…6 This necessity drives the development and evaluation of sustainable analytical methods for favipiravir bioanalysis, aiming to align with global sustainability goals and promote safer laboratory practices. Several analytical techniques have been utilized to analyze favipiravir, including spectrophotometry, [7][8][9] spectrouorimetry, [10][11][12] high performance liquid chromatographyultraviolet detector (HPLC-UV), [13][14][15][16] capillary electrophoresis, 17 liquid chromatographytandem mass spectrometry (LC-MS/MS) [18][19][20][21][22] and high performance thin liquid chromatography (HPTLC). 16 These methods have been applied to pharmaceutical dosage forms 7,8,11 and biological uids such as plasma, [13][14][15][16]18,19,21,[23][24][25][26][27][28][29][30] serum, 20,[31][32][33] and milk.…”

“…Several analytical techniques have been utilized to analyze favipiravir, including spectrophotometry, [7][8][9] spectrouorimetry, [10][11][12] high performance liquid chromatographyultraviolet detector (HPLC-UV), [13][14][15][16] capillary electrophoresis, 17 liquid chromatographytandem mass spectrometry (LC-MS/MS) [18][19][20][21][22] and high performance thin liquid chromatography (HPTLC). 16 These methods have been applied to pharmaceutical dosage forms 7,8,11 and biological uids such as plasma, [13][14][15][16]18,19,21,[23][24][25][26][27][28][29][30] serum, 20,[31][32][33] and milk. 29 Green Analytical Chemistry (GAC) has gained attention since 2000, with the goal of establishing safe analytical methodologies for both individuals and the environment.…”

“…Several analytical techniques have been utilized to analyze favipiravir, including spectrophotometry, 7–9 spectrofluorimetry, 10–12 high performance liquid chromatography – ultraviolet detector (HPLC-UV), 13–16 capillary electrophoresis, 17 liquid chromatography – tandem mass spectrometry (LC-MS/MS) 18–22 and high performance thin liquid chromatography (HPTLC). 16 These methods have been applied to pharmaceutical dosage forms 7,8,11 and biological fluids such as plasma, 13–16,18,19,21,23–30 serum, 20,31–33 and milk. 29…”

Facile synthesis and eco-friendly analytical methods for concurrent estimation of selected pharmaceutical drugs in their solutions: application to quality by design, lean six sigma, and stability studies

“…RSM can efficiently reduce the analysis cost by minimizing the number of experimental trials [ 3 – 10 ]. In the recent past, before the implementation of Six Sigma, almost pharmaceutical factories were suffering from high scrap and reprocessing without prior detection of an error, so the applications of the six-sigma methodology have become imperious in pharmaceutical industries to avoid wasting time, removing defects, and increase capability index in the process [ 11 – 13 ]. The stability study aims to offer data concerning how the performance of the pharmaceutical product varies gradually due to environmental variables such as light, humidity, and temperature, as well as to determine the shelf life of the drug product [ 14 ].…”