Advancing eco-engineered quality-by-design framework for sustainable chromatographic co-analysis of piroxicam and venlafaxine: A holistic greenness, whiteness, and blueness profiling

The analysis of multicomponent mixtures through High-Performance Liquid Chromatography constitutes a robust and precise analytical strategy for elucidating the composition and behavior of complex substances. This study introduces, for the first time, an experimentally designed HPLC method for the simultaneous quantification of piroxicam and venlafaxine hydrochloride in their pure forms, synthetic mixtures, single and combined dosage forms. Moreover, chromatographic optimization was carried out using a 2³ full factorial design to attain superior analytical efficiency and robustness while simultaneously minimizing time, labor, and solvent usage. On a C18 column, chromatographic separation was carried out using isocratic elution. 25 % phosphate buffer adjusted to pH 3.0, 60 % ethanol, and 15 % methanol made up the mobile phase and delivered at a flow rate of 1.2 mL/min. UV detection was conducted at 226 nm. The proposed method was rigorously validated in alignment with the International Council for Harmonization (ICH) guidelines. Calibration curves for piroxicam and venlafaxine hydrochloride exhibited exceptional linearity within the concentration ranges of 3.0–90.0 μg/mL and 4.5–200.0 μg/mL, respectively. The limits of detection were determined to be 0.979 μg/mL for piroxicam and 0.718 μg/mL for venlafaxine hydrochloride, while the limits of quantification were 2.96 μg/mL and 2.18 μg/mL, respectively. Another benefit is that the separation and quantification can be completed in less than 3 min. Also, the method fulfills all criteria of greenness, whiteness and blueness. In addition, the method's superior selectivity, precision, operational simplicity and rapidity collectively underscore its suitability for implementation in analytical quality control laboratories.