Evaluating the Performance of the LotusStream Gas-Liquid Separator for Preparative Supercritical Fluid Chromatography

Importance of the Topic

Preparative supercritical fluid chromatography (SFC) is widely used for large-scale purification in pharmaceutical, chemical, and natural-product research. Effective gas–liquid separation is critical to achieve high recovery rates and prevent sample loss or cross-contamination when CO2 transitions from supercritical fluid to gaseous state.

Study Objectives and Overview

This technical report evaluates the performance of the newly developed LotusStream™ gas–liquid separator integrated into a Shimadzu Nexera UC Prep system. Key goals include assessing recovery efficiency for compounds of differing volatility and solubility, measuring contamination in adjacent collection tubes, and determining carryover after instrument rinsing.

Methodology

Recovery, contamination, and carryover assessments were conducted using standard operating procedures and comparative liquid chromatography (LC) benchmarks:

• Recovery Evaluation: 1 mL injections of caffeine, linalool, and hydrocortisone under preparative SFC conditions; fractions collected in 100 mL flasks; reinjected to calculate recovery rate.
• Contamination Check: Linalool separation with multi-fraction system; eluate collected in adjacent tubes; samples diluted 2000× and reinjected to quantify carry-over into neighboring containers.
• Carryover Assessment: Hydrocortisone injections followed by a 2-minute rinse of the separator and flow path; eluate collected post-rinse, diluted 1000×, and reinjected to measure residual analyte.

Used Instrumentation

• Shimadzu Nexera UC Prep Stacked Fraction System and Multi-Fraction System
• LotusStream™ patented gas–liquid separator
• FRS-40 and FRC-40SF fraction collectors
• High-pressure SFC cell, back-pressure regulator, PDA detector, LCMS-2020 for reinjection analyses

Main Results and Discussion

Recovery rates using the LotusStream separator consistently exceeded 96% for all test compounds (caffeine 97.4%, linalool 98.9%, hydrocortisone 96.5%) with relative standard deviations below 0.6%. Contamination of adjacent test tubes during linalool separation was below the detection limit, corresponding to under 0.006%. Carryover after a two-minute rinse was measured at just 0.024% for hydrocortisone, demonstrating effective removal of non-volatile residues.

These results confirm that the LotusStream separator minimizes liquid splatter during CO2 expansion, enhances analyte recovery, and reduces sample carryover and cross-contamination compared to traditional separators.

Benefits and Practical Applications

• Improved purification yields in preparative SFC workflows
• Reliable recovery for both volatile and low-solubility compounds
• Low cross-contamination for sequential fraction collections
• Reduced rinse times and solvent usage for instrument maintenance

Future Trends and Applications

Advancements may include further optimization of flow-channel geometries, integration with automated fractionation software, and adaptation to continuous-flow preparative platforms. Miniaturization of gas–liquid separators and application to chiral and high-throughput workflows are promising directions.

Conclusion

The LotusStream gas–liquid separator offers a robust solution for preparative SFC by delivering high recovery rates, minimal contamination, and negligible carryover. Its implementation can streamline large-scale separations, reduce solvent consumption, and improve laboratory throughput in pharmaceutical and industrial analytics.