A Greenness-Assessed Chromatographic Method for Dolutegravir: Quality by Design-Based Development and Validation

Dolutegravir (DTG), used in HIV therapy, requires precise quantification, and its increasing focus on sustainability necessitates an eco-friendly analytical procedure. In this study, a reverse-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated using quality by design (QbD) principles to quantify DTG in bulk and finished pharmaceutical products. A quadratic design based on the response surface methodology was applied to refine the key method parameters, such as solvent proportion, flow rate, and column temperature. The optimized conditions consisted of water: methanol (۶۰:۴۰ v/v) with detection at ۲۵۷ nm. The method was validated according to ICH Q۲ (R۱) guidelines. The environmental impact of the method was evaluated using the AGREE, analytical eco-Scale, complementary green analytical procedure index (Complex GAPI), blue applicability grade index (BAGI), and assessment of green profile (AGP), providing a comprehensive view of its sustainability. The method demonstrated excellent performance outcomes, including strong linearity over ۱۲.۵۰–۷۵.۰۰ µg/mL (R² = ۰.۹۹۹۵), high precision with %RSD < ۱.۵ % for intra- and inter-day studies, and robust system behavior despite variations in solvent ratio, flow rate, and temperature. The greenness results further highlight the strengths of the method, with AGREE (۰.۶۹), Analytical Eco-Scale (۸۲), and BAGI (۷۷.۵) scores, confirming its alignment with environmentally conscious analytical practices. Overall, these findings confirm that the QbD-assisted RP-HPLC method is accurate, reliable, robust, and environmentally sustainable for routine quantification of DTG. Therefore, this is a practical and eco-friendly choice for pharmaceutical quality control.

کلیدواژه ها:

Method Development ، Validation ، Greenness Analysis ، Dolutegravir ، QbD ، RP-HPLC ، Green chemistry