Metal–Organic Frameworks for Glucocorticoid Determination: Extraction Strategies, Electrochemical Sensors, and Future Translational Perspectives
Abstract
Glucocorticoids (GCs), including dexamethasone, prednisolone, hydrocortisone, and betamethasone, are widely used in anti-inflammatory and immunosuppressive therapy. However, their reliable determination in pharmaceutical formulations, biological fluids, and environmental samples remains challenging because of trace concentration levels, complex sample matrices, and stringent sensitivity requirements. Conventional analytical techniques such as high-performance liquid chromatography, ultraviolet–visible spectrophotometry, and liquid chromatography–tandem mass spectrometry provide high sensitivity and selectivity but often require costly instrumentation, labor-intensive sample preparation, and centralized laboratory facilities. Metal–organic frameworks have recently emerged as promising analytical materials owing to their high surface area, tunable pore structures, and versatile surface chemistry. This critical review summarizes recent advances in MOF-assisted glucocorticoid analysis with particular emphasis on sample preparation, extraction strategies, electrochemical sensing, and analytical performance. MOF-based extraction systems, including MIL-101(Cr), MIL-53(Al), and Fe₃O₄/g-C₃N₄/MIL-101 composites, have demonstrated enhanced preconcentration efficiency and improved detection limits for glucocorticoids in complex matrices. In parallel, electrochemical and surface plasmon resonance (SPR)-based sensing platforms incorporating MOFs, molecularly imprinted polymers, conductive materials, and metallic nanoparticles have shown rapid response, high sensitivity, and promising selectivity for pharmaceutical, clinical, and anti-doping applications. The review further discusses structure–property relationships governing analytical performance, current limitations associated with aqueous stability, metal-ion leaching, matrix interference, and reproducibility, and recent strategies to improve robustness through hybrid architectures and rational material design. Particular attention is given to Fe- and Zr-based frameworks, which exhibit favorable chemical stability and biocompatibility for analytical applications. Overall, MOFs represent a versatile platform for next-generation glucocorticoid extraction and sensing. Future developments should focus on standardized analytical validation, matrix-dependent performance assessment, scalable green synthesis, MOF–MIP hybrid materials, and portable sensing technologies to facilitate reliable real-world implementation.