Analytical Method Development of a Stability-Indicating RP-HPLC Technique for Simultaneous Estimation of Metformin and Sitagliptin in Combined Dosage Forms

Abstract

The present study focuses on the development and validation of a stability-indicating reverse-phase high-performance liquid chromatography (RP-HPLC) method for the simultaneous estimation of Metformin hydrochloride and Sitagliptin phosphate in combined dosage forms. Owing to the increasing use of fixed-dose combinations for the treatment of type 2 diabetes mellitus, a robust analytical method is essential for ensuring quality control and regulatory compliance. Method development was carried out on a C18 column using a mobile phase of phosphate buffer (pH 4.5) and acetonitrile (60:40 v/v) at a flow rate of 1.0 mL/min, with detection at 260 nm. The method achieved well-resolved peaks with retention times of 3.10 and 6.52 minutes for Metformin and Sitagliptin, respectively. Validation, in accordance with ICH Q2(R1) guidelines, demonstrated specificity, linearity (r² > 0.999), accuracy (recoveries 98–102%), and precision (%RSD < 2). Forced degradation studies under acidic, alkaline, oxidative, thermal, and photolytic stress conditions confirmed the stability-indicating capability, as the method successfully separated drugs from their degradation products without interference. System suitability parameters, including theoretical plates (>5000), tailing factors (~1.0), and resolution (>2), confirmed robustness and reproducibility. Compared with previously reported methods, the proposed technique offers simplicity, cost-effectiveness, and shorter run time while retaining regulatory compliance. The developed RP-HPLC method is therefore suitable for routine analysis, stability testing, and quality control of fixed-dose formulations containing Metformin and Sitagliptin.