Hydrophilic Interaction Chromatography Techniques and Applications
Summary
Hydrophilic interaction chromatography (HILIC) has emerged as a pivotal separation technique for polar and hydrophilic analytes in complex matrices. By employing a polar stationary phase—typically silica or bonded zwitterionic, amino or diol derivatives—and an organic-rich mobile phase, HILIC achieves high retention of water-soluble compounds through a combination of partitioning into an adsorbed water layer and specific surface interactions. Advances in stationary-phase design have broadened the scope of HILIC, encompassing amino acid-derivative and zwitterionic phases that enhance selectivity and robustness. Integration of retention-modelling strategies, including adsorption and mixed-mode models, has accelerated method development and facilitated prediction of gradient-coupled separations, especially in proteomics and glycomics. Applications span from pharmaceutical impurity profiling and metabolite quantification to environmental monitoring of polar contaminants. The technique’s compatibility with mass spectrometry and laser-induced fluorescence detection underscores its role in high-throughput analyses. Continued innovation in column chemistry, mobile-phase optimisation, and computational approaches is driving global adoption of HILIC for routine and high-end research applications.
Research from Nature Portfolio
No recent Nature Portfolio content available.
Hydrophilic Interaction Chromatography Techniques and Applications publication trend
The graph below shows the total number of articles in hydrophilic interaction chromatography techniques and applications across all publications each year (not limited to Nature Index journals).
Technical terms
Hydrophilic interaction chromatography (HILIC): A mode of liquid chromatography employing a polar stationary phase and organic-rich mobile phase to retain hydrophilic analytes.
Stationary phase: The solid material within a chromatography column bearing functional groups that interact with analytes.
Retention factor (k): The ratio of the time an analyte spends in the stationary phase to the time in the mobile phase.
Gradient elution: A technique in which the composition of the mobile phase is varied during a run to improve separation efficiency.
Adsorbed water layer: The water-rich film immobilised on polar stationary phases that forms the primary retention medium in HILIC.
References
- Surface Modification of Silica with β‑Alanine Derivatives for Unique Applications in Liquid Chromatography. ACS Applied Materials & Interfaces (2023).
- Evaluating the Adsorbed Water Layer on Polar Stationary Phases for Hydrophilic Interaction Chromatography (HILIC). Separations (2019).
- Applicability of retention modelling in hydrophilic-interaction liquid chromatography for algorithmic optimization programs with gradient-scanning techniques. Journal of Chromatography A (2017).
- Accurate modelling of the retention behaviour of peptides in gradient-elution hydrophilic interaction liquid chromatography. Journal of Chromatography A (2019).
About these summaries
This Nature Research Intelligence Topic summary is created with the cited references and a large language model. We take care to ground generated text with facts, and have systems in place to gain human feedback on the overall quality of the process in line with our AI principles. We strive to create accurate and useful summaries for people unfamiliar with the research topic and that supports this goal. These pages are a beta release and will be updated as we learn how best to help people gain value from a research topic summary.
Turn complex research questions into confident strategic decisions
When you're under pressure to set direction, justify investment, or understand your competitive position, you need more than raw data — you need trusted insights you can act on.
Benchmark your performance against global peers using robust, methodologically sound analysis.
Combine quantitative metrics with qualitative expert insight to uncover strengths, gaps and emerging opportunities.
Gain tailored, decision-ready recommendations aligned to your strategic priorities.
Talk to us to learn more about our data dashboards and bespoke strategy reports.
Grow research skills, confidence and careers with training built for every stage of the research lifecycle.
Developed with Nature Portfolio journal Editors and internationally renowned experts. Discover three ways to learn:
Self-paced, online courses in convenient bite-sized units, covering key skills across scientific writing, publishing, grant writing, data analysis, and more.
Expert trainer-led workshops with hands-on exercises and real-time feedback across core research skills, delivered via interactive group sessions.
Editor-led workshops combining core principles in writing and publishing, personalised 1:1 feedback from Nature Portfolio Editors and hands-on exercises.
Explore course catalogues and workshop agendas, enquire about the options or request institutional pricing.