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This Reprint investigates the implementation of highly effective technologies based on chromatographic techniques to separate complex compound mixtures in difficult matrices. It highlights recent scientific findings in separation science, with a strong focus on the development of advanced analytical protocols. A central theme of this collection is the application of these chromatographic techniques in environmentally friendly processes. The compiled research presents innovative analytical systems, sample preparation ideas, and extraction methodologies that promote green analytical chemistry. By bringing together modern studies on compound separation and sustainable technologies, this Reprint serves as a comprehensive resource for researchers and practitioners working to minimize environmental impact while maintaining high analytical performance in the laboratory.