Supercritical Fluid Chromatography (SFC): A Review on Key Technique of Green Analytical Chemistry in Advanced Pharmaceutical Spectral Analysis

Abstract

This review provides an in‐depth examination of Supercritical Fluid Chromatography (SFC) as a key analytical technique in advanced pharmaceutical spectral analysis. Emphasizing its evolution over recent decades, the paper outlines how SFC has emerged as a robust alternative to traditional chromatographic methods such as High-Performance Liquid Chromatography (HPLC) and Gas Chromatography (GC). By utilizing supercritical carbon dioxide as the primary mobile phase, often modified with polar co-solvents, SFC achieves rapid separations, enhanced resolution, and reduced solvent consumption. These advantages are particularly beneficial in the analysis of complex pharmaceutical formulations, where precise impurity profiling, chiral separations, and stability testing are critical. The review discusses the fundamental principles governing SFC, including solubility, partitioning mechanisms, and chiral recognition, while also detailing the instrumentation advancements that have expanded its applicability. Special attention is given to the integration of advanced detection techniques, such as mass spectrometry and diode array detection, which have significantly enhanced spectral analysis capabilities. Moreover, the paper explores the role of SFC in driving forward green chemistry practices by minimizing hazardous solvent usage. Overall, this review underscores the transformative potential of SFC in pharmaceutical research and quality control, positioning it as an indispensable tool for ensuring drug safety, efficacy, and compliance with stringent regulatory standards.