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SFC Basic Guide - Shimadzu Supercritical Fluid Chromatograph

Guides | 2025 | ShimadzuInstrumentation
SFC
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Summary

Significance of the Topic


The transition from conventional liquid chromatography to supercritical fluid chromatography reduces net CO2 emissions by using recycled carbon dioxide and minimizes organic solvent waste. This supports global efforts to combat climate change and fosters greener analytical workflows.

Objectives and Overview


This guide outlines the principles of supercritical fluid chromatography (SFC), contrasts SFC with gas chromatography and high performance liquid chromatography, and highlights recent technological advances that have made SFC a routine laboratory technique. It covers fundamental properties of supercritical fluids, analytical advantages of SFC, preparative applications, and complete system configurations.

Used Methodology and Instrumentation


Analysis by SFC relies on the unique physical properties of supercritical carbon dioxide combined with organic modifiers. Key instrument elements include:
  • Pumps designed for liquefied CO2 and separate pumps for organic modifiers and make up solvents
  • Back pressure regulators to maintain fluid state throughout flow channels
  • Column ovens and a variety of stationary phase choices spanning normal phase and reversed phase media
  • Detectors such as UV visible, evaporative light scattering, and mass spectrometry compatible with rapid CO2 depressurization
  • Online and offline supercritical fluid extraction modules that automate sample pretreatment for solid materials

Main Results and Discussion


SFC using supercritical carbon dioxide offers several analytical advantages:
  • Low polarity mobile phase similar to hexane yields improved structural selectivity and chiral separations
  • Solvent miscibility with modifiers such as methanol or ethanol enables analysis of a broad polarity range from fatty acids to peptides
  • Low viscosity and high diffusion coefficients permit ultra fast separations with maintained resolution
  • Rapid depressurization of CO2 at detection enhances LC MS sensitivity by reducing matrix dilution
  • Preparative separations benefit from minimal post processing as CO2 evaporates and targets are collected with high recovery rates

Benefits and Practical Applications


Applied examples illustrate the practical value of SFC:
  • Simultaneous analysis of hundreds of pesticides in food matrices covering very hydrophilic to hydrophobic compounds
  • Automated screening of chiral columns and organic modifiers to optimize enantiomeric separations of pharmaceutical intermediates
  • Rapid extraction and analysis of bioactive components from plant materials using integrated supercritical fluid extraction and chromatography
  • Fast screening of inhaled drug formulations and related impurities by online SFE SFC QTOF MS
  • Preparative purification of volatile aroma compounds with minimal solvent handling and high purity fractions

Future Trends and Potential Applications


Advances likely to shape SFC workflows include:
  • Enhanced method scouting software with automated modifier mixing and column switching for high throughput development
  • New stationary phases tailored for mixed mode interactions to resolve challenging isomers and polar analytes
  • Wider adoption of online SFE SFC MS in metabolomics and environmental screening for rapid sample to result analysis
  • Expanded use of preparative SFC in pharmaceutical and natural product purification to reduce solvent costs and simplify post processing

Conclusion


Supercritical fluid chromatography now offers a powerful and environmentally friendly alternative to conventional GC and HPLC. By leveraging the unique properties of supercritical CO2 with modern instrumentation and software, SFC delivers fast, high resolution separations across a wide chemical space with reduced solvent consumption and waste.

References


  • Simultaneous analysis of water soluble and fat soluble vitamins by unified SFC LC chromatography J Chromatogr A 2014 1362 270 277
  • Retention behavior in subcritical fluid chromatography with varied polarity stationary phases J Sep Sci 2008 31 1238 1251
  • van Deemter plots for supercritical fluid chromatography Chromatographia 1987 21 14 25
  • Supercritical fluid chromatography fundamentals and applications Technical Report Shimadzu 2021 C190 E200
  • Comparison of retention in SFC and normal phase HPLC with diverse stationary phases Molecules 2019 24 2425
  • High throughput phospholipid profiling by SFE SFC MS J Chromatogr B 2012 1076 196 204

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