Application of Green Analytical Chemistry in Pharmaceutical Drug Analysis: Sustainable and Eco-Friendly Analytical Methods

Abstract

ABSTRACT Pharmaceutical quality control and drug analysis laboratories consume massive quantities of toxic organic solvents, generate hazardous chemical waste, and expend substantial energy annually. Green Analytical Chemistry (GAC) has emerged as a fundamental paradigm shift aimed at minimizing or eliminating the environmental and ecological footprint of analytical methodologies without compromising methodological rigor, sensitivity, precision, or regulatory compliance. This comprehensive review critically examines the strategic integration of GAC principles into pharmaceutical drug analysis. We systematically evaluate green chromatography, including Supercritical Fluid Chromatography (SFC), Eco-Friendly High-Performance Liquid Chromatography (HPLC) utilizing benign mobile phases (e.g., ethanol, water, bio-based ionic liquids, deep eutectic solvents), and Ultra-High Performance Liquid Chromatography (UHPLC) designed for ultra-low solvent consumption. Furthermore, advanced solventless and microextraction sample preparation techniques—such as Solid-Phase Microextraction (SPME), Stir Bar Sorptive Extraction (SBSE), and Liquid-Phase Microextraction (LPME)—are rigorously benchmarked against traditional liquid-liquid extraction (LLE). Quantitative greenness assessment tools (NEMI, GAPI, AGREE, and RGB fast model) are analyzed for their utility in validating eco-friendly protocols. Through comprehensive comparative evaluations, this review highlights recent green analytical breakthroughs for key Active Pharmaceutical Ingredients (APIs), assesses operational and economic hurdles in quality control environments, and outlines future perspectives driven by microfluidic lab-on-a-chip technologies and artificial intelligence-optimized chromatographic separations.

KEYWORDS: Green Analytical Chemistry; Pharmaceutical Analysis; Eco Friendly HPLC; Deep Eutectic Solvents; Supercritical Fluid Chromatography; AGREE Metric; Sample Preparation.