A stability-indicating RP-HPLC method for quantification of impurities in sertraline hydrochloride finished dosage forms using quality by design with environmental assessment

Sertraline hydrochloride is a widely prescribed antidepressant used in the management of depression and anxiety disorders. The control of impurities is essential to ensure the safety, efficacy, and quality of pharmaceutical products. The present study describes the development and validation of a simple, robust, supported favorable environmental performance, and stability-indicating RP-HPLC-UV method for the determination of impurities in sertraline hydrochloride finished dosage forms using an Analytical Quality by Design (AQbD) approach. Chromatographic separation was achieved on an ACE5 C18 PFP column (250 × 4.6 mm, 5 µm) using a gradient mobile phase comprising phosphate buffer (pH 4.2), methanol, and acetonitrile at a flow rate of 1.0 mL min⁻¹, with UV detection at 254 nm. Critical method parameters were optimized using a three-level, two-factor Design of Experiments (DoE), and a design space was established to ensure method robustness. Forced degradation studies under various stress conditions confirmed the stability-indicating nature of the method. The developed method provided complete resolution of all impurities and degradation products with high specificity. Validation results demonstrated excellent linearity over the approximate concentration range of 0.2–5.0 µg mL⁻¹ (R² > 0.999), along with satisfactory accuracy, precision, sensitivity, and robustness. Greenness assessment using AGREE and GAPI tools yielded scores of 0.79 and 84, respectively, confirming the environmental sustainability of the method. The proposed AQbD-based and favorable environmental performance method is suitable for routine quality control and stability testing of sertraline hydrochloride pharmaceutical formulations.