Automated Optimization of Chiral Separation Parameters Using Nexera UC Chiral Screening System

Importance of the Topic

Chiral compounds are central to many pharmaceutical and agrochemical products, where the two enantiomers can exhibit markedly different biological activities. Traditional HPLC methods for chiral analysis often require normal phase conditions with significant solvent use and lengthy method development. Supercritical fluid chromatography (SFC) offers a high-speed, low-viscosity alternative using supercritical CO₂ with polar modifiers. Automating the optimization of chiral SFC parameters can dramatically accelerate method development and reduce solvent consumption and environmental impact.

Objectives and Study Overview

This study aimed to demonstrate the capabilities of the Nexera UC chiral screening system for automated scouting of separation conditions. Using omeprazole as a model compound, the system evaluated 36 combinations of 12 Daicel CHIRALPAK®/CHIRALCEL® columns and three modifier types (methanol, ethanol, acetonitrile/ethanol) under a programmed gradient. The goal was to rapidly identify optimal column–modifier pairs that achieve baseline separation of enantiomers within a practical analysis timeframe.

Methodology and Used Instrumentation

The screening workflow involved automatic switching among columns and modifier compositions. Key analytical conditions included:

• Mobile phase A: Supercritical CO₂
• Mobile phase B: Methanol, ethanol, or acetonitrile/ethanol (3:1, v/v)
• Gradient: 20% B (0–8 min) to 40% B (8–10 min) back to 20% B (10–14 min)
• Flow rate: 3 mL/min; Column temperature: 40 °C; Back pressure: 10 MPa
• Injection volume: 2 µL; Detection by photodiode array (210–400 nm max-plot)

Used instrumentation:

• Shimadzu Nexera UC chiral screening system
• Daicel CHIRALPAK® (IA, IB, IC, ID, IE, IF, AD, AS, AY) and CHIRALCEL® (OD, OJ, OZ) 3 µm, 100 mm × 3 mm I.D. columns
• Supercritical fluid delivery module and column oven
• Photodiode array detector

Main Results and Discussion

All 36 conditions were evaluated, and enantiomeric separation of omeprazole was achieved in under 8 minutes. The top-ranked method employed CHIRALCEL® OZ-3 with methanol modifier, delivering a resolution of 7.97 and separation factor of 1.92. Secondary ranking favored CHIRALPAK® IC-3 with methanol (resolution 5.59) and with ethanol (resolution 5.38). The automated ranking tool effectively filtered chromatograms exceeding resolution criteria (≥1.5), simplifying the selection of the best analytical conditions. Comparative analysis highlighted how different stationary phases and modifier polarities influence retention, selectivity, and peak symmetry.

Benefits and Practical Applications

• Rapid method development through automated scouting avoids manual column and solvent trials.
• Reduced organic solvent consumption and shorter analysis times lower operating costs and environmental impact.
• Reliable ranking of separation quality supports quality control and research workflows in pharmaceutical and chemical industries.

Future Trends and Potential Applications

Advances may include integration of machine learning to predict optimal chiral separations, expansion of screening libraries to novel stationary phases and greener modifiers, and real-time feedback loops for automated method refinement. The approach could be extended to complex mixtures, high-throughput enantiomeric purity testing, and regulatory compliance applications.

Conclusion

The Nexera UC chiral screening system enables streamlined, automated optimization of SFC parameters for chiral analysis. By evaluating multiple column–modifier combinations in a single unattended run, it substantially reduces method development time and solvent usage while delivering high-resolution enantiomer separations. This platform supports efficient, sustainable workflows for chiral compound analysis.

References

No formal literature references were provided in the source document.