Green analytical evaluation of anticancer drug analysis: A multi-tool assessment of HPLC and LC-MS methods

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.