Advantages of using immobilized stationary phases in chiral separations

Significance of the Topic

Polysaccharide‐based chiral stationary phases are central to modern enantiomeric separations, particularly in pharmaceutical, agrochemical and fine‐chemical industries. Their multiple chiral centres and attached aromatic groups provide broad chiral recognition. Immobilizing these selectors on silica expands solvent compatibility and enhances column robustness, enabling reliable resolution of challenging enantiomeric pairs.

Objectives and Overview

This article evaluates the advantages of immobilized versus coated polysaccharide chiral stationary phases. It aims to demonstrate how covalent attachment of chiral selectors to silica extends solvent choice, maintains selectivity under aggressive conditions and improves practical method development for enantiomeric resolution.

Methodology and Instrumentation

A variety of cellulose derivatives were compared in normal‐phase and polar‐organic modes. Key instrumentation details include:

• Columns: 250 x 4.6 mm ID, 5 µm Lux i-Cellulose‐5 (immobilized) and Lux Cellulose‐1 (coated).
• Elution: Isocratic runs using MtBE with 0.1 % ethylamine or hexane/ethanol with 0.1 % diethylamine.
• Flow rates: 1.0–1.5 mL/min; detection via UV absorbance at 220–280 nm; ambient temperature.
• Injection solvent studies employed strong organics such as dimethyl sulfoxide (DMSO).

Results and Discussion

Immobilized Cellulose‐5 columns achieved baseline separation of ornidazole when methyl tert‐butyl ether (MtBE) with ethylamine was used, outperforming the coated Cellulose‐1 phase with hexane/ethanol mixtures. The immobilized phase maintained high resolution despite injections of strong organic solvents; whereas coated phases risk dissolution and loss of selectivity, the covalent linkage in immobilized phases prevented degradation and ensured consistent performance over repeated runs.

Benefits and Practical Applications

• Expanded Solvent Range: Covalent attachment allows use of aggressive solvents, improving screening flexibility.
• Enhanced Stability: Immobilized phases resist dissolution and maintain selectivity under demanding conditions.
• Single‐Column Workflow: A single chiral column can support normal‐phase, reversed‐phase, polar‐organic and supercritical fluid chromatography.
• Improved Method Development: Broader mobile phase options accelerate optimization for difficult enantiomer pairs.

Future Trends and Applications

Advances in selector chemistry may yield new polysaccharide derivatives with tailored binding pockets. Integration with supercritical fluid chromatography and 2D‐LC systems promises faster throughput and greener processes. Additionally, miniaturized immobilized CSPs could enhance chiral screening in microfluidic and online reaction monitoring applications.

Conclusion

Immobilized polysaccharide chiral stationary phases offer superior solvent compatibility, durability and selectivity compared to coated analogues. Their versatility simplifies chiral method development and supports reliable enantiomeric purity analysis across a wide range of compounds.

References

1. Polysaccharide‐based chiral stationary phase literature on immobilization techniques
2. Comparative studies of coated vs. immobilized cellulose phases in enantiomeric separations
3. Application notes on chiral separations of ornidazole using Lux chiral columns