Optimizing Preparative Workow with the LH-40 Liquid Handler

Importance of the Topic

Preparative liquid chromatography is a key technique for isolating target compounds at high purity from complex mixtures. It is widely used in pharmaceutical development, natural product research and chemical synthesis. Efficient preparative workflows reduce solvent consumption, sample waste and operator time while maintaining high recovery and purity, making optimization critical in routine and high-throughput applications.

Objectives and Study Overview

This study demonstrates how the Shimadzu Nexera Prep system, equipped with the LH-40 liquid handler and LabSolutions control software, can streamline the entire preparative LC workflow. The report covers preliminary analytical investigations, scale-up to preparative conditions, fraction collection, purity verification and scalable high sample throughput using multiple LH-40 units.

Applied Instrumentation

• Shimadzu Nexera Prep preparative purification LC system
• LH-40 liquid handler combining autosampler and fraction collector
• LC-40D analytical pump and SPD-40V UV detector
• LC-20AP preparative pump and SPD-M40 UV detector
• Shim pack Scepter C18 columns 250 mm x 4.6 mm ID and 250 mm x 20 mm ID particle size 5 micron
• LabSolutions control software

Methodology

Initial separation conditions were evaluated on an analytical scale by injecting up to 400 microliters into a 4.6 mm ID C18 column. Retention times, peak shapes and loading volumes were determined to estimate sample capacity. Scale-up to preparative scale employed geometrically proportional adjustments to column internal diameter, flow rate and injection volume. Fraction collection parameters were configured automatically or by time windows within LabSolutions. Collected fractions were analyzed directly by the LH-40 on the analytical flow path for purity assessment without manual sample transfer.

Main Results and Discussion

Scale-up from a 4.6 mm ID column at 1 mL per minute to a 20 mm ID column at 19 mL per minute maintained identical chromatographic performance. Automatic fraction collection based on signal slope and threshold simplified peak isolation, while time based methods ensured consistent fractionation across runs. Purity checks of fractions showed single compound peaks above 99 purity for each target. Coupling two LH-40 units enabled processing up to 72 samples with five fractions each in a continuous workflow, demonstrating high sample throughput.

Benefits and Practical Applications

• Fully integrated workflow from method development to purity verification in a single system
• Reduced manual intervention and minimized solvent and sample handling
• Flexible fraction collection modes to accommodate retention time variability
• High throughput capability by coupling up to six LH-40 units for sequential processing of large sample sets

Future Trends and Opportunities

Advancements in preparative LC are expected to focus on increased automation, integration with lab information management systems and application of artificial intelligence for method optimization. Miniaturized preparative columns and solvent recycling technologies may further reduce resource consumption. Expanded multiunit configurations will address growing demands in pharmaceutical purification and combinatorial chemistry.

Conclusion

The combination of the LH-40 liquid handler and LabSolutions software within the Nexera Prep platform streamlines preparative LC workflows, enabling efficient scale-up, automated fraction collection and inline purity checks. The system supports high-purity isolations and high throughput applications by coupling multiple liquid handlers, making it a versatile solution for pharmaceutical, chemical and natural product laboratories.

References

• Koterasawa K Asakura H Nakajima K Osaka Y Funada Y Matsumoto K Watanabe K Optimizing Preparative Workflow with the LH-40 Liquid Handler Shimadzu Technical Report C190 E277 2021