Bioanalytical Approaches for the Quantitative Determination of SGLT2 Inhibitors in Biological Matrices: A Comprehensive Review

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a significant class of antidiabetic medications that also provide documented cardiovascular and kidney protection. It is essential to quantify these drugs precisely in biological matrices such as plasma, serum, and tissues. The quantification aids pharmacokinetic studies, assists bioequivalence establishment, and facilitates therapeutic monitoring. This review outlines the key bioanalytical methods established for their quantitation. These techniques include liquid chromatography-tandem mass spectrometry (LCMS/MS), which is the most suitable because of its high selectivity, sensitivity, and capability to detect the substance at very low concentrations. Highperformance liquid chromatography (HPLC), often coupled with ultraviolet detection, is also a common and inexpensive option for regular analysis. Ultra-performance liquid chromatography (UPLC) has become popular due to its rapid run times and enhanced separation efficiency, thus being a suitable option for high-throughput analysis. The review also considers usual sample preparation techniques, including protein precipitation, liquid-liquid extraction, and solidphase extraction, and how they impact recovery, selectivity, and matrix effects. It addresses validation criteria such as accuracy, precision, linearity, detection limits, quantitation limits, and analyte stability, according to international guidelines. Although LC-MS/MS represents the norm in practice today, UPLC methods are gaining increasing recognition for their speed and analytical potential