Sodium-glucose co-transporter-2 (SGLT2) inhibitors ("gliflozins"), foundational cardiorenal therapeutics usually co-formulated with metformin and dipeptidyl-peptidase-4 inhibitors as fixed-dose combinations (FDCs), have an overwhelmingly experimental, computationally shallow analytical literature. This critical review examines in silico approaches to analytical and bioanalytical method development and to forced-degradation and stability profiling, then compares software platforms, separating gliflozin-specific evidence from prospective capability. From structure alone, computation reproduces the class's defining analytical problem: a several-log-unit polarity gap between neutral, moderately lipophilic gliflozins and hydrophilic cationic metformin. Property and ADME prediction is reliable only for rank-ordering, because inter-algorithm log P estimates diverge. Computer-assisted retention modelling with design of experiments, the most mature contribution, supports a defensible ICH Q14 method operable design region (MODR); quantitative structure-retention relationships, computationally designed molecularly imprinted polymers, and in silico degradation and impurity prediction remain largely prospective. ICH M7(R2) recommends two complementary (Q)SAR methodologies for potentially mutagenic impurities. The clearest opportunities are coupling degradation-pathway prediction to LC-HRMS to identify degradants prospectively, a first step toward closing the forced-degradation mass-balance gap, and externally validated retention models spanning the polarity gap. Every prediction (log P, retention time, degradant, docking score) is a hypothesis for experimental confirmation, never a substitute for validation.
β-lactam antibiotics, widely used in human and veterinary medicine, can trigger serious public health concerns through misuse-including antimicrobial resistance and drug residues. The detection of β-lactam antibiotics faces three challenges: unstable β-lactam rings prone to hydrolysis, complex metabolism requiring multi-residue analysis, and trace-level concentrations (μg/kg) with severe matrix interference demanding high sensitivity and accuracy. Thus, systematically optimizing sample analytical methods is essential to enhance monitoring programs and ensure food safety. This review offers a comprehensive overview of contemporary pretreatment methodologies, encompassing well-established techniques such as solid-phase extraction and dispersive liquid-liquid microextraction, as well as innovative approaches including solidification floating organic droplet liquid-liquid microextraction and electromembrane extraction. Recent advancements in pretreatment strategies for β-lactam antibiotics are increasingly oriented toward achieving high extraction and purification efficiency, enhancing environmental sustainability, and improving the reusability of extraction materials. By critically evaluating the advantages and limitations of various techniques, this review aims to support progress in detection accuracy and reliability, increase analytical throughput and efficiency, and reduce operational costs.
