Multi-dimensional sustainability assessment framework for micellar UPLC and spectrophotometric analysis of a three-drug combination and its genotoxic impurity

Abstract

This study introduces an innovative framework for comprehensive sustainability assessment of analytical methods, applied to the simultaneous determination of acebrophylline, montelukast, fexofenadine, and the genotoxic impurity bromobenzene. A newly developed micellar ultra-performance liquid chromatography (UPLC) method, employing a Kinetex HILIC column and an eco-friendly mobile phase of sodium dodecyl sulfate and 18 % 1-pentanol, offers reduced organic solvent use while achieving robust separation. Additionally, we report the first implementation of a suite of green spectrophotometric methods (direct zero-order, ratio subtraction, second and third derivative, and double-divisor ratio derivative) using only water as solvent for this four-component system. All methods demonstrated excellent analytical performance with appropriate linearity ranges (r² ≥ 0.999), recovery (98.5–101.5 %), and precision (RSD ≤2 %). The sustainability profile was assessed through a novel multi-dimensional approach integrating environmental impact (NEMI, ComplexGAPI, AGREE), practical applicability (BAGI), innovation potential (VIGI), and overall sustainability (RGB12). Carbon footprint analysis showed minimal environmental impact (0.002 and 0.039 kg CO₂ equivalent per sample for spectrophotometric and UPLC methods, respectively). The newly introduced Need, Quality, Sustainability (NQS) index quantified holistic sustainability, with the proposed methods achieving superior scores across all metrics compared to existing techniques. The NQS Index assessment confirmed strong alignment with SDGs, including SDGs 3 (Good Health), 6 (Clean Water), 9 (Innovation), 12 (Responsible Consumption), 13 (Climate Action), 14 (Life Below Water), and 15 (Life on Land). This integrated assessment framework advances analytical methodology evaluation beyond traditional performance metrics, introducing a holistic approach to quantify and visualize multiple sustainability dimensions in microanalytical chemistry.