The Analytical Evolution of Glibenclamide (Glyburide) Antidiabetic Agents: Analytical Tools, Challenges, and Future Trends

Glyburide (glibenclamide), a second-generation sulfonylurea, remains a cornerstone in the management of type 2 diabetes mellitus. However, its narrow therapeutic index and typically low plasma concentrations demand highly sensitive and reliable quantification methods for applications spanning pharmacokinetics, therapeutic drug monitoring, clinical diagnostics, pharmaceutical quality control, and environmental surveillance. This review provides a critical overview of four decades of methodological progress in glyburide analysis, synthesizing evidence from major scientific databases, including Scopus, Web of Science, ScienceDirect, PubMed, and Google Scholar. High-performance liquid chromatography (HPLC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) have emerged as the gold-standard approaches, offering exceptional sensitivity, specificity, and reproducibility across diverse matrices. In contrast, spectrophotometric methods provide cost-effective and straightforward options for routine analyses, while electrochemical techniques, particularly voltammetry with nanotextured electrodes, demonstrate remarkable sensitivity, sustainability, and applicability to trace detection. Capillary electrophoresis, though less commonly adopted, offers distinct benefits in resolution and solvent economy. Critical challenges are highlighted, including the quantification of glyburide at clinically relevant levels (2-400 ng/mL in plasma, with LOD as low as 0.038 ng/mL and LOQ 1.5 ng/mL), as well as overcoming matrix interferences and stability issues. Rigorous method validation remains essential to ensure accuracy and clinical utility. Finally, this review identifies key future directions, emphasizing the integration of green analytical chemistry principles, miniaturized platforms, and nanostructured sensing technologies to advance selective, sensitive, and environmentally sustainable glyburide analysis. These innovations hold the potential to transform glyburide monitoring from laboratory-based methods to real-world applications, including point-of-care testing and environmental health monitoring.