GREEN ANALYTICAL CHEMISTRY IN RP-HPLC METHOD DEVELOPMENT FOR ANTIDIABETIC FIXED-DOSE COMBINATIONS: A COMPREHENSIVE REVIEW WITH SPECIAL REFERENCE TO METFORMIN HYDROCHLORIDE AND DAPAGLIFLOZIN

*Mr. Mohammad Zameeruddin, Ms. Pooja Bhimrao Lamdade

Abstract

The growing prevalence of type 2 diabetes mellitus (T2DM) and the increasing clinical preference for fixed-dose combinations (FDCs) have necessitated the development of reliable, sensitive, and environmentally responsible analytical methods for the simultaneous quantification of antidiabetic drug combinations. Metformin hydrochloride (MET), a first-line biguanide antidiabetic agent, and Dapagliflozin (DAPA), a novel sodium-glucose cotransporter-2 (SGLT-2) inhibitor, represent a clinically significant FDC increasingly prescribed in T2DM management. This review critically examines the principles of green analytical chemistry (GAC) as applied to reversed-phase high-performance liquid chromatography (RP-HPLC) method development, with emphasis on the simultaneous estimation of MET and DAPA in pharmaceutical formulations. The review covers the pharmacological background of both drugs, physicochemical properties relevant to HPLC method design, green analytical chemistry principles and assessment tools (NEMI, GAPI, AGREE, Eco-Scale), chromatographic method development strategies, ICH Q2(R1) validation parameters, regulatory requirements, and a critical appraisal of published RP-HPLC methods for this drug combination. Emerging trends including ultra-high-performance liquid chromatography (UHPLC), green mobile phase alternatives, and multivariate optimization approaches are also discussed. This review serves as a comprehensive reference for analytical scientists developing sustainable chromatographic methods for antidiabetic FDCs.

Keywords: Green Analytical Chemistry, RP-HPLC, Metformin Hydrochloride, Dapagliflozin, Fixed-Dose Combination, ICH Q2(R1) Validation, SGLT-2 Inhibitor, Method Development, AGREE, NEMI.