QbD‐Assisted RP‐HPLC Method Development and Validation for the Quantification of Sotagliflozin With LC–MS/MS Characterization of Its Degradation Products and Greenness Assessment Using AGREE and MoGAPI

ABSTRACT

An AQbD‐based approach was employed to develop and validate a reliable, stability‐indicating RP‐HPLC method for quantifying sotagliflozin in API and tablet dosage forms. Sotagliflozin, a dual SGLT‐1/2 inhibitor used in diabetes management and cardiovascular risk reduction, requires a sensitive and robust analytical method for quality control and stability assessment. Critical method parameters were screened using a Taguchi design and optimized through Box–Behnken Design (BBD). Chromatographic separation was achieved on an Agilent Zorbax SB‐C18 column using an eco‐friendly mobile phase comprising ethanol and 0.1% TFA (pH 2.25) in a 38:62% v/v ratio at a flow rate of 1 mL/min, yielding excellent system performance. The method was validated according to ICH guidelines, demonstrating good linearity (25–150 μg/mL), precision, accuracy, robustness, and sensitivity with low LOD and LOQ values. Forced degradation studies confirmed its stability‐indicating capability, with notable degradation under acidic (11.03%), alkaline (14.13%), oxidative (12.39%), and thermal (14.49%) conditions, while minimal degradation occurred under hydrolytic and photolytic stress. LC–MS/MS enabled identification and structural characterization of four major degradation products. Greenness assessment using AGREE and MoGAPI tools yielded scores of 0.89 and 91, respectively, confirming the method's eco‐friendly nature for routine pharmaceutical analysis.