Why is Supercritical Fluid Chromatography Making a Comeback?
Introduction
In early 2026, the Chinese Journal of Pharmaceutical Analysis published a research paper by researchers from the School of Pharmacy, Fudan University and the Shanghai Institute for Drug Control and Research (formerly Shanghai Institute for Food and Drug Control). The study employed supercritical fluid chromatography (SFC) with an Ultisil Cellu-D chiral column from Welch Materials as the stationary phase to separate vildagliptin, an antidiabetic drug, from its R-enantiomer.
The method used supercritical carbon dioxide–methanol (90:10) containing 0.2% diethylamine and 0.2% trifluoroacetic acid as the mobile phase, and a resolution of up to 2.7 has been achieved.
What is SFC, and what are the differences between SFC and HPLC? In this article, we will explore this unsung hero which is gaining renewed attention in today's pharmaceutical analysis.
What is SFC: Look Beyond Conventional Chromatography
Let us forget about the stereotypes the word "chromatography" brought to us, and ask a simple question: what is a supercritical state?
Matter is commonly encountered in three states: solid, liquid, and gas. However, when a substance is heated and pressurized beyond its critical point, it enters a unique "fourth" state, where it combines gas-like low viscosity and high diffusivity with liquid-like solvent power. SFC features supercritical carbon dioxide (scCO₂) in this state as the primary mobile phase.
One may ask: why carbon dioxide? This is because carbon dioxide is non-toxic, non-flammable, chemically inert, readily available, and has relatively mild critical conditions (31.1°C and 7.39 MPa).
How Does SFC Work?
An SFC system combines supercritical CO₂ with a mobile phase modifier to achieve chromatographic separation. First, CO₂ from a cylinder passes through a cooling and delivery pump, while the modifier solvent is delivered by a separate pump. Then, just like HPLC, the two streams are mixed to form the mobile phase, which then passes through an autosampler (which introduces the sample) and enters an SFC column, where the sample components are separated.
Why is SFC Gaining Momentum?
The renewed interest in SFC rests on three principal advantages: speed, sustainability, and strength in chiral separation.
Speed: The low viscosity and high diffusivity of supercritical CO₂ significantly reduce mass-transfer resistance compared with conventional HPLC, enabling fast separations. In a comparative study on the separation of chiral sulfoxide enantiomers, Kolderová et al. demonstrated that an SFC method could achieve a separation in just 3 minutes that required 12 minutes by HPLC.
Sustainability: Traditional HPLC consumes substantial quantities of organic solvents, including acetonitrile, methanol, n-hexane, and isopropanol. With CO₂ being used as the primary mobile phase, organic solvent consumption in SFC can be reduced by more than 80%. The Chinese Pharmacopoeia 2025 Edition has recognized SFC as a greener alternative technology, with 50 drug products selected for pilot implementation.
Strength: SFC is widely regarded as one of the most promising techniques for chiral separation. According to published data, 64% of the 506 new molecular entities approved by the FDA between 2002 and 2022 were chiral drugs. Among the 62 small-molecule drugs approved in 2023 and 2024, more than 90% contained chiral centers, and 86% were marketed as single enantiomers. Chiral separation is where SFC excels.
What Can SFC Do?
Recent research shows that the application landscape of SFC is expanding rapidly. In chiral drug separation, SFC has been successfully applied to the enantiomeric separation of tegoprazan, sitagliptin phosphate, linagliptin, lansoprazole, sertraline, and ezetimibe, besides vildagliptin. In complex impurity analysis, SFC enables the simultaneous separation and quantification of seven isomeric and non-isomeric impurities in brivaracetam, as well as the analysis of 15 impurities in semisynthetic paclitaxel in a single run.
In lipidomics, SFC can be used to analyze complex lipid classes, including fatty acids, glycerides, and phospholipids. In food analysis, SFC is used in the analysis of nutrients and bioactive compounds.
Market Outlook
According to market research reports, the global SFC market was valued at approximately USD 1.63 billion in 2025 and is projected to reach USD 2.25 billion by 2033. North America currently holds the largest market share, at approximately 39.6%, while Asia-Pacific is expected to be the fastest-growing regional market in the following years.
Key growth drivers include rising demand for high-throughput analysis in the pharmaceutical and biotechnology industries, increasingly stringent requirements for chiral separation, and the broader adoption of greener, more sustainable analytical technologies.
Advancing Your SFC Capabilities with Welch Materials
The Ultisil Cellu-D column featured in the study introduced at the beginning of this article belongs to an earlier generation of Welch Materials' chiral column portfolio.
Today, Welch Materials offers the next-generation Blossmate chiral column series, comprising three major product categories: normal-phase coated, reversed-phase coated, and immobilized chiral columns.
Designed to address diverse separation challenges, the Blossmate series provides a comprehensive range of column options to support your analytical needs in both SFC and HPLC. For more information, please contact us at info@welchmat.com.
