What Is Supercritical Fluid Chromatography (SFC) And How It is Different From HPLC And GC

Supercritical Fluid Chromatography (SFC) is a type of normal-phase chromatography that uses a supercritical fluid—typically carbon dioxide—as the mobile phase. Ideal for separating low to moderate molecular weight, thermally labile, and chiral compounds, SFC shares similar principles with HPLC but operates under high pressure to maintain the supercritical state. Because supercritical fluids combine properties of both liquids and gases, SFC is also known as convergence chromatography—a concept first introduced by Giddings

Among the different chromatographic techniques, Supercritical Fluid Chromatography (SFC) is making waves — offering a greener, faster, and more efficient alternative to conventional methods like HPLC and GC. This blog will walk you through everything you need to know about SFC: from basic definitions to advanced applications.

What is Supercritical Fluid Chromatography (SFC)?

Supercritical Fluid Chromatography (SFC) is a separation technique that uses a supercritical fluid as the mobile phase to separate components in a mixture. A supercritical fluid exists at a temperature and pressure above its critical point, where it exhibits properties of both gases and liquids — low viscosity and high diffusivity like gases, but solvation power like liquids.

The most commonly used supercritical fluid in SFC is carbon dioxide (CO₂) due to its low toxicity, low cost, and relatively mild critical temperature (31.1°C) and pressure (73.8 bar).

Principle of SFC

The principle of SFC is similar to that of liquid chromatography:

• The sample is injected into the system.
• It is carried by the supercritical CO₂ (often modified with a polar organic solvent like methanol or acetonitrile) through a chromatographic column.
• Separation occurs based on differential partitioning of analytes between the mobile phase and the stationary phase.
• Detection (often UV, PDA, or mass spectrometry) follows.

Mobile Phase and Column in SFC

Mobile Phase:

• Primary: Supercritical CO₂
• Modifier/Additive: Small percentage (5–40%) of polar solvents like methanol, ethanol, or isopropanol to increase solubility and polarity range.

Column:

• Typically packed with silica-based stationary phases similar to HPLC.
• Both normal-phase and reversed-phase columns are used, depending on the application.
• Particle sizes are usually in the sub-2 µm to 5 µm range.

Step-by-Step Function of SFC

1. Sample Introduction: The analyte is injected into the mobile phase stream.
2. Pressurisation: CO₂ is pumped and pressurized above its critical point.
3. Modification: A co-solvent is mixed with CO₂ to enhance solubility of polar compounds.
4. Separation: The mixture flows through a column where components are separated based on their interaction with the stationary phase.
5. Detection: Detectors like UV, PDA, or MS detect the separated compounds.
6. Back Pressure Regulation: A back pressure regulator maintains the supercritical state of the CO₂ throughout the system.

Case Study: Application in Pharmaceutical Analysis

Use Case: Chiral Separation of Enantiomers in Drug Development

Pharmaceutical companies frequently use SFC to separate enantiomers of chiral drugs. For instance, ibuprofen, a chiral NSAID, has R- and S- enantiomers, only one of which is pharmacologically active. SFC offers rapid, high-resolution separation of enantiomers using chiral stationary phases and supercritical CO₂ — reducing analysis time and solvent use compared to HPLC.

Benefits in this context:

• Reduced analysis time (minutes vs. hours)
• Lower solvent consumption
• Better resolution of chiral pairs
• Scalability to preparative chromatography

Advantages of SFC

• Eco-friendly: Uses CO₂ instead of large volumes of organic solvents.
• Fast Analysis: Lower viscosity allows faster flow rates.
• Cost-effective: Reduced solvent usage and faster turnaround reduce operating costs.
• Versatile: Ideal for chiral, non-volatile, and thermally labile compounds.
• Scalable: Can be easily scaled up for preparative and industrial applications.

Limitations of SFC

• Limited to moderately polar compounds: CO₂ has low polarity; high-polarity compounds may require complex modifiers.
• System Complexity: Requires high-pressure pumps, back pressure regulators, and specialized equipment.
• Solubility Issues: Some compounds may have limited solubility in CO₂.
• Method Development: More complex and time-consuming than conventional HPLC.

Applications of SFC

• Pharmaceuticals: Chiral drug separation, impurity profiling, metabolite analysis.
• Food & Beverage: Detection of flavours, colours, and preservatives.
• Environmental: Pesticide residue and pollutant analysis.
• Cosmetics: Analysis of fragrance components.
• Petrochemicals: Separation of hydrocarbons and additives.

SFC vs. HPLC vs. GC

Conclusion

Supercritical Fluid Chromatography stands at the intersection of efficiency, sustainability, and versatility. Whether you’re working in a pharmaceutical lab or exploring new analytical methods, SFC offers a powerful alternative to traditional HPLC and GC — especially when analysing chiral compounds or seeking a greener approach.

As technology advances and environmental regulations tighten, SFC is poised to become a cornerstone of modern analytical science.

You may like:

1. Relative Response Factor (RRF) in Pharmaceutical Analysis
2. How To Control Impurities In Pharmaceuticals: Get Mastery In 11 Minutes
3. How To Calculate Potency, Purity and Assay In Pharmaceuticals

FAQs

Further Reading

1. Berger, T. A. (2002). Supercritical Fluid Chromatography: Principles and Practice. Oxford University Press.
   – This book provides a comprehensive overview of SFC theory, instrumentation, and practical applications.
2. SUPERCRITICAL FLUID CHROMATOGRAPHY