QbD-Driven Development of a Sustainable UPLC Method for Xanomeline and Trospium Chloride: A Multi-Metric Greenness Evaluation

Ultra-performance liquid chromatography (UPLC) remains a cornerstone in pharmaceutical analysis; however, the shift toward sustainable laboratory practices necessitates the development of ecologically conscious methodologies. This study presents a validated, greener UPLC method for estimation of Xanomeline (XAN) and Trospium Chloride (TRO) simultaneously which is a promising combination for managing schizophrenia and Alzheimer’s disease. Utilizing a Quality by Design (QbD) framework, the separation was optimized on a CHS C۱۸ column (۱۰۰mm × ۲.۱ mm, ۱.۸ µm) using a mobile phase of ۰.۱% trifluoroacetic acid with methanol in ratio of ۷۸:۲۲ with flow rate of ۰.۳ mL/min. The optimised method was rigorously validated as per guidelines of ICH Q۲ (R۱), which shows excellent linearity, precision, and accuracy. A pivotal aspect of this work was the multi-faceted assessment of environmental impact using nine distinct metrics. The method scored an Analytical Eco-scale score of ۹۳, signifying "Excellent Greenness," and an AGREE score of ۰.۸۳. Further evaluation via GAPI, NEMI, AGREE prep, Complex MoGAPI, BAGI, and RAPI tools confirmed a significantly reduced ecological footprint, characterized by minimal solvent waste and low energy consumption. This dual-purpose approach ensures that the method is not only analytically robust for regular quality control but also aligns with the global shift toward Green Analytical Chemistry (GAC).

کلیدواژه ها:

Ultra-Performance Liquid Chromatography (UPLC) ، Quality by Design (QbD) ، Xanomeline ، Trospium Chloride ، Analytical Greenness Assessment