SIMULTANEOUS RP-HPLC DETERMINATION OF ARMODAFINIL, CLONIDINE, AND VILOXAZINEHYDROCHLORIDE: ICH VALIDATION AND COMPUTATIONAL GREEN, BLUE, AND WHITE METRIC PROFILING
Attention-deficit/hyperactivity disorder (ADHD) is a widespread neurological condition commonly managed withacombination of armodafinil, clonidine, and viloxazine hydrochloride. Despite their concurrent clinical use, novalidated simultaneous analytical method exists for their quantification, representing a critical gap in pharmaceutical quality control. This study presents the development and ICH Q2(R1) validation of an environmentally sustainablereverse-phase high-performance liquid chromatography (RP-HPLC) method. A sustainable RP-HPLCmethodwasdeveloped for the simultaneous determination of three drugs in a single analytical run. Chromatographic separationwas performed on a Sunfire C18 column using a Waters 2695D system with UV detection at 230 nm. Separationwas conducted at a flow rate of 1.0 mL/min with an injection volume of 10 μL. The 14-minute run yielded wellresolved peaks with excellent linearity (R² > 0.99). Intraday and interday RSDs remained below 2%, confirminghigh precision and accuracy, while low LOD and LOQ values demonstrated adequate sensitivity, and robustness andsolution stability studies further validated its reliability for routine use. Comprehensive sustainability evaluationusing AGREE prep, AGREE, GAPI, GWAPE, WAC, and BAGI tools revealed superior greenness, blueness, andwhiteness scores compared to previously reported individual methods, demonstrating reduced solvent hazards, minimised waste generation, and enhanced analytical efficiency. The proposed method provides a scientificallyvalid, economical and eco-compatible solution to the simultaneous pharmaceutical quality check analysis, withdirect applicability to regulatory submissions and industrial laboratory workflows. Its green analytical profile further positions it as a model for sustainable method development in multi-drug formulation analysis.
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