Eco-Friendly Analytical Methods for Quantitative Estimation: A Critical Review of Green and White Analytical Chemistry Approaches in Pharmaceutical Analysis

Green Analytical Chemistry (GAC) has matured from a conceptual add-on into a quantifiable design criterion for methods used in the quantitative estimation of pharmaceuticals. Over the past decade, more than ten distinct greenness-assessment tools have emerged — from the qualitative National Environmental Method Index (NEMI, 2008) to fully quantitative, software-assisted metrics such as AGREE (2020), AGREEprep, Complex-GAPI, the Analytical Method Greenness Score (AMGS), and the 2024–2025 generation of tools including MoGAPI and the Analytical Green Star Area (AGSA). In parallel, White Analytical Chemistry (WAC) and complementary indices such as BAGI have emerged to balance environmental greenness against analytical performance and practicality ("Red" attributes), recognizing that a method optimized purely for greenness can sacrifice sensitivity or robustness. This review synthesizes the 2020–2025 literature on eco-friendly quantitative-estimation methods for pharmaceuticals, compares the principal greenness-assessment tools on their scoring logic and known limitations, and surveys recent applications combining Design of Experiments/AQbD optimization with green-solvent selection in HPLC-based quantitative estimation. Persistent gaps are identified in tool standardization, integration of greenness scoring into formal AQbD control strategies, and consistent joint reporting of green and white metrics.