Huma Sulthana, Judy Jays, Prakash Kumar B., Prakash S. Goudanavar
The escalating global cancer burden necessitates sustainable analytical methods for therapeutic drug monitoring of antineoplastic agents, yet conventional HPLC and LC-MS protocols predominantly employ hazardous solvents. This study presents comparative greenness evaluation of chromatographic methods specifically for anticancer drugs, applying eight complementary GAC tools AGREE, MoGAPI, AGREEprep, Analytical Eco-Scale, BAGI, CACI, CaFRI, and AGSA to 20 published analytical methods (16 HPLC and 4 LC-MS). Z-score standardization enabled composite rankings, with Pearson correlation analysis confirming strong inter-tool agreement (AGREE-BAGI: r = 0.858, p < 0.001 in HPLC cohort). Results showed marked variability in sustainability, with top performing methods achieving high scores (HPLC Method 1: AGREE 0.57, AES 86, composite Z-score 1.541; LC-MS Method 3: AGREE 0.61, composite Z-score 0.983). Optimized HPLC methods outperformed LC-MS counterparts in reagent safety, waste reduction, and energy efficiency. Critically, no method incorporated genuinely green solvents. The multi-metric framework provides quantitative benchmarks for method optimization via solvent substitution, miniaturization, and automation. By identifying practical and eco-friendly analytical routes for anticancer drug analysis, this study promotes greener pharmaceutical research and advocates integration of greenness metrics into regulatory guidelines.