UV-Vis Spectrophotometric Determination of Multicomponent Pharmaceuticals: Limitations, Severity-Driven Strategies, and Method Selection

Abstract

Multicomponent pharmaceutical products, particularly fixed-dose combinations (FDCs), have become increasingly important in modern therapeutics to improve patient adherence and therapeutic outcomes. Although chromatographic techniques are widely employed for their analysis, ultraviolet-visible (UV-Vis) spectrophotometry remains an attractive alternative owing to its operational simplicity, cost-effectiveness, and broad accessibility. Nevertheless, the simultaneous spectrophotometric determination of multiple active pharmaceutical ingredients is intrinsically challenging due to extensive spectral overlap, limited method selectivity, disparities in absorptivity and dosage ratios, restricted linear concentration ranges, and matrix interference from formulation excipients. To address these challenges, a variety of mathematical, spectroscopic, and chemometric strategies have been developed, including derivative and ratio spectrophotometry, dual-wavelength and difference techniques, and multivariate calibration approaches such as principal component regression and partial least squares. This review critically evaluates the principal analytical limitations encountered in multicomponent UV-Vis spectrophotometric analysis and systematically summarizes the strategies used to overcome them. Particular emphasis is placed on severity-driven, decision-based method selection, method validation considerations, and regulatory alignment with ICH Q2(R2) and ICH Q14 guidelines. By integrating analytical challenges with structured mitigation strategies and workflow-based guidance, this work provides a comprehensive framework for the rational development and fit-for-purpose application of spectrophotometric methods in multicomponent pharmaceutical analysis.