Evolution of Pregabalin Analytical Methods: A Comprehensive Assessment of Performance, Accessibility, and Future Directions.

Analytical determination of pregabalin presents unique challenges due to its aliphatic structure and absence of chromophoric groups, despite its classification as a BCS Class I drug with high solubility and permeability. This comprehensive review critically evaluates and compares the diverse analytical methodologies developed over the past two decades for pregabalin quantification in pharmaceutical formulations and biological matrices. We systematically analyze titrimetric, spectroscopic (UV-Vis, fluorescence, and infrared), electrochemical, chromatographic (HPTLC, HPLC, GC), and mass spectrometric techniques, with particular emphasis on derivatization strategies that overcome pregabalin's inherent detection limitations. Comparative assessment of these methods reveals significant variations in sensitivity (LOD ranging from 19.00 μg/mL to 4.9 ng/mL), selectivity, complexity, and applicability across different matrices. This review provides analytical chemists with a decision framework for method selection based on specific analytical requirements, available instrumentation, and sample characteristics. Our analysis identifies emerging trends in pregabalin analysis, including the increasing adoption of green analytical approaches, miniaturized techniques, and hyphenated systems that enhance both sensitivity and specificity while reducing environmental impact.