Challenge‐Oriented Decision Tree for Analytical Method Selection in Metformin, Sodium–Glucose Cotransporter‐2 (SGLT2) Inhibitors and Dipeptidyl Peptidase‐4 (DPP‐4) Inhibitors Triple Antidiabetic Fixed‐Dose Combinations in Pharmaceutical Dosage Forms

Triple fixed-dose combinations (FDCs) comprising metformin, sodium-glucose cotransporter-2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors have become an important therapeutic option for type 2 diabetes mellitus but present significant analytical challenges owing to differences in dose ratio, polarity, ionization behaviour, solubility, ultraviolet absorption and chemical stability. This review critically evaluates analytical methods for the simultaneous determination of these combinations in pharmaceutical dosage forms, including ultraviolet spectrophotometry, high-performance thin-layer chromatography, reversed-phase and ultra-performance liquid chromatography, capillary electrophoresis and liquid chromatography-tandem mass spectrometry. Rather than describing published methods individually, the review comparatively assesses analytical performance, robustness, validation quality, stability-indicating capability, greenness and suitability for routine pharmaceutical quality control within the context of ICH Q2(R2), ICH Q14, USP <1220> and Analytical Quality by Design (AQbD). A major contribution is the development and retrospective validation of a challenge-based decision framework that integrates physicochemical properties, analytical objectives, regulatory requirements, laboratory capabilities and sustainability principles to support rational method selection. Validation against published methods demonstrated strong agreement with reported analytical strategies. Future perspectives highlight the potential of artificial intelligence, advanced chemometrics and emerging chromatographic technologies to advance analytical development for complex multicomponent pharmaceutical products.