Shimadzu Solutions for Medicinal Chemistry

Importance of the Topic

The development of efficient, high-throughput separation techniques is essential in medicinal chemistry to accelerate chiral screening, preparative purification, and compound identification. By integrating supercritical fluid chromatography (SFC), ultrahigh-performance liquid chromatography (UHPLC), and advanced software solutions, laboratories can significantly reduce method development time, maximize instrument utilization, and ensure high-purity isolations for drug discovery and quality control.

Objectives and Overview

This collection of application notes presents Shimadzu’s Nexera UC series and related systems designed for analytical and preparative separations in medicinal chemistry. Key goals include:

• Streamline chiral method scouting using automated column and modifier switching.
• Improve preparative SFC recovery rates with novel separators and stacking injections.
• Enable seamless UHPLC/SFC mode switching for rapid condition optimization.
• Support remote data review and sample management in LC/MS workflows.
• Integrate online concentration and trap purification for ultrafast preparative LC (UFPLC).

Methodology and Instrumentation

Major systems and components described:

• Nexera UC Chiral Screening SFC: automatic switching among 12 chiral columns and 4 modifiers with Method Scouting Solution software.
• Nexera UC Prep: semi-preparative SFC with LotusStream separator, compressor-cooled CO2 pump, stacked injection, and up to four detector channels.
• Nexera UC/s UHPLC/SFC Switching System: shared solvent delivery, autosampler, column oven, and detector for both modes with automatic mobile-phase and column switching.
• Open Solution Analytical LCMS: open-access sample login, automatic email notification, remote Data Browser review, and automatic flow-line washing.
• Nexera Prep LC and MS-Trigger LCMS: integrated fraction purity checks, sample rescue function, LH-40 liquid handler, and FRC-40 fraction collector supporting multiple tube formats.
• UFPLC System: online fractionation, trap concentration, counter-ion removal, and rapid drying for high-purity recovery of trace and volatile compounds.
• Daicel CHIRALPAK and CHIRALCEL columns: 12 polysaccharide-derivative stationary phases for SFC chiral separations.

Main Results and Discussion

Analytical and preparative performance highlights:

• Chiral Screening: 36 SFC conditions screened overnight; analysis time reduced to one-third to one-fifth of conventional HPLC.
• LotusStream Separator: achieved 96.7% recovery of 1% linalool versus 78.0% with standard separators, independent of flow rate or modifier concentration.
• Stacked Injection: enabled nine consecutive injections in the time of three, tripling sample throughput.
• Multi-Detector Prep: UV and MS triggering allowed high-purity fraction collection of low-UV-absorbing components.
• UHPLC/SFC Reproducibility: five-cycle switching demonstrated stable retention times and peak shapes across both modes for multiple chiral drugs.
• Remote LCMS Access: sample submission, run monitoring, and data processing fully accessible via networked Data Browser without local software installation.
• Fraction Purity & Rescue: integrated purity checks during preparative runs and recovery of residual sample after process interruptions.
• UFPLC Efficiency: reduced fraction and drying times by >50%; on-column trapping and counter-ion removal delivered high-concentration, free-base fractions rapidly.

Benefits and Practical Applications

The combined systems offer:

• Acceleration of method development through automated condition scouting.
• Reduced labor and downtime by continuous overnight runs and remote monitoring.
• Enhanced lab footprint efficiency by sharing modules across SFC and UHPLC.
• Improved fraction purity and recovery yields in preparative workflows.
• Flexibility to scale from analytical screening to preparative purification seamlessly.

Future Trends and Possibilities

Emerging opportunities include:

• Integration of machine-learning algorithms for predictive method scouting and automated parameter optimization.
• Development of greener mobile phases and supercritical solvent alternatives to further reduce environmental impact.
• Miniaturized, modular systems for benchtop continuous-flow purification and real-time analytics.
• Expanded online coupling of purification with high-resolution mass spectrometry and structure elucidation tools.
• Cloud-based data management platforms to enable global collaboration and data sharing in real time.

Conclusion

Shimadzu’s comprehensive suite of SFC, UHPLC/SFC switching, preparative LC, and UFPLC systems delivers a unified approach to analytical and preparative challenges in medicinal chemistry. By combining advanced hardware innovations with specialized software workflows, laboratories can achieve faster screening, higher recovery rates, improved purity, and greater operational flexibility, supporting accelerated drug discovery and development.

Reference

• No specific literature references were provided in the source document.