Comprehensive assessment of HPLC methods for atorvastatin using different tools: A step towards sustainable...

The present study provides a comprehensive assessment of thirty reported high-performance liquid chromatography (HPLC) methods for the determination of atorvastatin using seven green analytical chemistry (GAC) evaluation tools, including HEXAGON, Analytical Method Volume Intensity (AMVI), Chloroform-oriented Toxicity Estimation (ChlorTox), Red-Green-Blue fast model (RGBfast), Modified Green Analytical Procedure Index (MoGAPI), Analytical GREEnness (AGREE), Analytical Eco-Scale, one white analytical chemistry (WAC) evaluation tool, namely Blue Applicability Grade Index (BAGI) and one redness evaluation tool, Red analytical performance index (RAPI). These tools were applied to systematically evaluate analytical performance in terms of solvent consumption, toxicity, energy usage, waste generation, and method applicability.

AMVI values ranged from 50 to 315 mL/component, indicating substantial differences in solvent consumption among the evaluated HPLC methods. ChlorTox values varied between 0.006929 and 0.499461, reflecting differences in the toxicity profiles of the solvents employed. AGREE scores ranged from 0.54 to 0.72, while Analytical Eco-Scale scores varied from 63 to 87, identifying several methods with excellent greenness characteristics. MoGAPI scores ranged from 64 to 77, classifying majority of methods as moderately green. BAGI scores between 65 and 82.5 indicated moderate to excellent applicability for routine analytical use. RAPI scores ranged from 22.5 to 77.5, demonstrating considerable variation in analytical performance, from poor to very good validation quality. RGBfast assessment further highlighted differences in analytical efficiency, environmental sustainability, and practical applicability among the evaluated methods. Overall, methods characterized by low solvent consumption, lower solvent toxicity, and strong analytical performance exhibited the highest sustainability, whereas methods requiring higher solvent volumes and employing more hazardous solvents showed greater environmental burden.

The study highlights the importance of integrating multiple greenness tools to guide the development and selection of environmentally sustainable analytical methods.