A Green and QbD‐Optimized Rp‐Hplc Method for Simultaneous Estimation of Linagliptin and Dapagliflozin

ABSTRACT The present study focuses on the development and optimization of a robust reversed‐phase high‐performance liquid chromatography (RP‐HPLC) method for the simultaneous estimation of linagliptin and dapagliflozin in bulk and tablet dosage forms. A Quality by Design (QbD) approach was employed using the Box‐Behnken design to systematically optimize critical chromatographic parameters, ensuring efficient separation with high sensitivity and reproducibility. The optimized conditions utilized a mobile phase of methanol: acetonitrile: buffer: triethylamine (80:10:10:0.1 v/v/v/v), with a pH adjusted to 5.0 using orthophosphoric acid and a flow rate of 1.0 mL/min. The method demonstrated excellent linearity (r 2 > 0.998), precision (%RSD < 2), and accuracy (98.9%–100.5%), complying with ICH guidelines. Additionally, a greenness evaluation was conducted using the AGREE analytical greenness metric tool, giving a score of 0.68, indicating an environmentally sustainable analytical approach. The developed method is rapid, reliable, and suitable for routine quality control analysis of linagliptin and dapagliflozin in pharmaceutical formulations.