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

Abstract

The introduction of favipiravir as a broad-spectrum antiviral agent, particularly in treating influenza and exploring its potential against COVID-19, emphasizes the necessity for efficient analytical methods. Liquid chromatography has emerged as a commonly utilized technique for quantifying favipiravir in biological fluids. However, the environmental and health concerns linked to classical analytical methods mean a transition toward green analytical chemistry is required. This study investigates the environmental impact of 19 liquid chromatographic methods utilized in the bioanalysis of favipiravir. Recognizing the importance of eco-friendly practices in pharmaceutical analysis, the study employs three widely accepted greenness assessment tools: Analytical Eco-Scale (AES), Green Analytical Procedure Index (GAPI), and Analytical Greenness Calculator (AGREE). Moreover, it incorporates a comprehensive evaluation on a global scale utilizing the whiteness assessment tool Red-Green-Blue 12 (RGB 12). The comprehensive evaluation aims to extend beyond traditional validation criteria and considerations of green chemistry, providing insights into the development of practically efficient, eco-friendly and economical analytical methods for favipiravir determination. This study emphasizes the necessity of planning for the environmental impact and overall sustainability of analytical methods before laboratory trials. Additionally, the integration of greenness/whiteness evaluation in method validation protocols is strongly advocated, emphasizing the importance of critical and global evaluations in analytical chemistry.

Fig. 1. Chemical structure of the antiviral agent favipiravir.

Fig. 2. Comparison of the whiteness profiles of the 19 methods for determining favipiravir in biological fluids using the RGB 12 algorithm. Red criteria (method performance) included scope of application (R1); lower limit of quantification (R2); precision (R3) and accuracy (R4). Green criteria (method greenness) included: toxicity of reagents (G1); amounts of reagent and waste (G2); energy consumption (G3) and direct impacts (G4). Blue criteria (method effectiveness) included: cost-efficiency (B1); time-efficiency (B2); requirements: sample consumption and the need for advanced instruments and skilled personnel (B3) and operational simplicity (B4).

Fig. 3. Comparison of the main assessment outcomes of the 19 methods used to determine favipiravir in biological fluids, as derived from the RGB 12 analysis. The white dotted line represents 100%, indicating complete suitability for the planned application.