<p>The primary aim of the current research was to develop and validate a cost-effective, environment benign and rapid reverse phase high-performance liquid chromatography for the quantification of Posaconazole in its bulk and marketed formulation. The Inertsil ODS-3V (250 × 4.6&#xa0;mm, 5 μ) column was used for chromatographic separation with the mobile phase of methanol: water (95:05) at the flow rate of 1&#xa0;mL/min and the wavelength for analysis was set at 260&#xa0;nm. The chromatographic condition was determined and the retention time was found to be 3.379&#xa0;min. To assess whether the method is eco-friendly and economical, green and white tools were used such as, analytical eco-scale, analytical greenness calculator, modified green analytical procedure index, blue applicability grade index, red green blue fast and red analytical performance index. These tools verified that the optimised chromatographic method was both environmentally benign and feasible. Additionally, the suggested analytical method demonstrated that all the validation parameter was performed as per ICH Q₂R₁ recommendations and all the parameters are within the acceptable range. The calibration curve showed a linear in the concentration range of 1 to 25&#xa0;µg/mL with a correlation coefficient of 0.9999. The proposed method has several advantages over the previously reported RP-HPLC method and may be used to systematically investigate posaconazole in its formulation.</p> Graphical Abstract <p></p>