A-QbD-based green RP-HPLC method for estimation of rivaroxaban in pharmaceutical dosage forms

Abstract This work reports the Analytical Quality by Design (AQbD) based green RP-HPLC method for Rivaroxaban, aimed at delivering a sustainable and robust analytical approach. A systematic AQbD framework was applied to define the QTPP and select critical analytical attributes, leading to an optimized method using an Ascentis C18 column. The analysis was carried out at a constant temperature of 40 °C with a mobile phase flow rate of 1 ml min⁻¹ and UV detection at 250 nm. A 5µL aliquot of standard solution was injected using an isocratic mobile phase of water pH 3 and ethanol (60:40v/v). The method produced a sharp Rivaroxaban peak at 2.51 min, with excellent linearity ( r = 0.999) and high accuracy (99.40%), confirming its precision, reliability, and suitability for routine use. Greenness was evaluated using five independent tools AES, NEMI, GAPI, AGREE, and the RGB model. The method demonstrated good eco-friendliness, reflected by an AES score of 79%, a favourable NEMI pictogram, a GAPI profile indicating moderate environmental impact, an AGREE score of 0.62, and an RGB greenness value of 75.2%. Collectively, these assessments show high consistency across tools and confirm that the developed AQbD-based method offers a strong balance of analytical performance and environmental sustainability. Overall, this study provides a validated, rapid, economical, and green RP-HPLC procedure that supports improved sustainability in pharmaceutical quality-control testing while maintaining regulatory-compliant analytical reliability.