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.