Analytical Method for the Determination of Sglt2 Inhibitors in Biological Matrices: A Comprehensive Review

In this review‚ we summarize and critically discuss existing analytical procedures developed for the determination of SGLT2 inhibitors in bioanalytical matrices since they have become major players in the management of T2DM in an insulin-independent manner‚ with some kind cardiovascular and kidney outcomes․ Amongst the majority of prescribed drugs of this drug class‚ dapagliflozin‚ empagliflozin‚ and canagliflozin are the most widely used SGLT2 inhibitors․ The analysis of biologic fluids such as plasma‚ serum‚ and urine is also necessary for pharmacokinetics‚ therapeutic drug monitoring‚ and monitoring medication adherence․ This review discusses a variety of sample clean-up techniques including protein precipitation‚ liquid-liquid extraction‚ solid-phase extraction‚ and various types of microextraction․ Each of these techniques has its own advantages and disadvantages with regards to sensitivity‚ selectivity‚ and throughput․ Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the gold standard analytical method because of its higher sensitivity and specificity with the ability to detect at ng/mL concentrations․ Strong method validation (accuracy‚ precision‚ linearity‚ limit of detection and matrix effects) is fundamental for quantification in complex biological matrices‚ yet matrix effects‚ low analyte concentrations‚ prohibitive instrumentation and variation in sample preparation methods often complicate the analytical community's pursuit for accurate and reproducible results․ High throughput‚ low-cost‚ and green analytical methods as well as Ultra High Performance Liquid Chromatography (UHPLC)‚ High Resolution Mass Spectrometry (HRMS)‚ and microsampling methods are likely to dominate future approaches․ Stronger analytical methods also need to be developed to improve treatment options and the clinical management of diabetes overall.