Separation and Purification of Bioactive Natural Products from Complex Biological Matrices

Dear Colleagues,

Bioactive natural products, sourced from plants, microorganisms, marine organisms, and other biological systems, continue to serve as a vital foundation for drug discovery, functional food development, cosmeceutical innovation, and agrochemical design. However, their effective separation and purification from complex biological matrices—such as crude extracts, fermentation broths, tissues, and bodily fluids—pose substantial technical hurdles. These challenges are compounded by the vast chemical diversity of natural metabolites, wide polarity distributions, frequent low abundance of target compounds, coextraction of interfering substances (e.g., lipids, pigments, proteins, and polysaccharides), and the presence of closely related structural analogues that are difficult to resolve.

This Special Issue, titled "Separation and Purification of Bioactive Natural Products from Complex Biological Matrices" focuses on innovative strategies, advanced technologies, and integrated workflows that address the unique obstacles encountered when isolating highpurity bioactive molecules from biologically derived source materials. We invite original research articles, communications, and comprehensive reviews that showcase significant progress in sample preparation, selective enrichment, highresolution separation, and final purification, with particular attention to sensitivity, reproducibility, throughput, scalability, and green chemistry principles.

Topics of interest include, but are not limited to, the following:

• Advanced chromatographic methods (e.g., preparative HPLC, highspeed countercurrent chromatography, flash chromatography, and multidimensional LC) tailored for complex matrix fractionation;
• Novel stationary phases, monolithic columns, and multimodal separation materials designed for selective capture of bioactive natural products;
• Hyphenated analytical platforms (e.g., LCMS/MS, LCNMR, LCHRMS) for targeted isolation and realtime structure annotation of minor bioactive constituents;
• Membrane filtration, solidphase extraction, molecularly imprinted polymers, and immunoaffinity techniques for matrix cleanup and preconcentration;
• Green and sustainable extractionpurification cascades (e.g., deep eutectic solvents, supercritical fluid extraction, enzymeassisted, and ultrasoundassisted processes) applied to biologically complex feeds;
• Bioactivityguided fractionation coupled with highresolution activity screening (e.g., microplatebased, online HPLCbioassay) to pinpoint active compounds directly from crude mixtures;
• Simulated moving bed chromatography, centrifugal partition chromatography, and other scalable purification technologies for industriallevel recovery;
• Strategies for removing major interferents (e.g., chlorophyll, tannins, sterols, and endotoxins) without compromising target bioactivity;
• Process analytical technology (PAT), qualitybydesign (QbD), and machinelearning models for optimizing separation conditions and predicting elution behavior in complex systems;
• Recycling and reusability of separation media, solvents, and stationary phases to enhance economic and environmental sustainability.

We cordially invite researchers from analytical chemistry, natural product chemistry, biochemical engineering, and pharmaceutical sciences to submit their latest findings and forwardlooking perspectives. Contributions that bridge fundamental understanding with practical solutions for realworld biological matrices are especially encouraged. All accepted papers will be rapidly published and widely disseminated to an international audience, fostering crossdisciplinary collaboration in this critically important field.

Dr. Chunying Li
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Separations is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• bioactive natural products
• complex biological matrices
• separation technologies
• purification techniques
• coupling technologies
• chromatography
• bioactivity
• guided fractionation
• prepared HPLC
• countercurrent chromatography
• green separation