Implementation of Analytical Quality by Design to Develop a Stability-Indicating RP-HPLC Method for Sotagliflozin
Year: 2026
Type: article
Abstract: This study applied Analytical Quality by Design (AQbD) approaches to systematically develop a stability-indicating RP-HPLC method for the quantification of sotagliflozin in both bulk drug substance and tablet formulations. The Analytical Target Profile (ATP) was determined to guide the selection of Critical Analytical Attributes (CAAs), namely retention time and tailing factor. The Critical Method Parameters (CMPs) including mobile phase composition, flow rate, and column temperature were optimized using a Box-Behnken design to effectively control the CAAs. Chromatographic separation employed a mobile phase of acetonitrile and 10 mM ammonium acetate buffer in a 60:40 (v/v) ratio. An isocratic mobile phase, adjusted to pH 3.0 with 0.05% ortho-phosphoric acid, was delivered at 1.0 mL min-1 through an ODS C18 column (250 mm × 4.6 mm i.d., 5 µm) maintained at 28 °C. Detection was conducted at 225 nm, corresponding to the λmax of sotagliflozin. Analysis of variance (ANOVA) test resulted in statistically significant linear model terms (p < 0.05). The developed method was validated following ICH guidelines which demonstrated linearity over 5-25 µg mL-1 (R² = 0.999), with LOD and LOQ of 0.12 and 0.38 µg mL-1, respectively. Forced degradation studies supported the stability-indicating nature of the method, with marked degradation under acidic (26.45%), alkaline (29.29%), and thermal (23.58%) conditions, while greater stability was observed under oxidative, hydrolytic, and photolytic stress. Therefore, this AQbD-based stability-indicating RP-HPLC method provides a robust and scientifically justified approach for the routine analysis of sotagliflozin, supporting reliable drug product stability assessment.
Institutions: University of Dhaka, East–West University, East West University
Language: English
Subfield: Analytical Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: diamond
OpenAlex ID: W7167488609