CFC Fraction Collectors Extend the Application of SFC

• Chiral Separations
• Isolation of Impurities from Reaction Products
• Fractionation of Natural Products and Complex Mixtures
• Isolation of Metabolites and Biomarkers
• Flash SFC

The HPLC-like convenience and functionality of Modular SFC’s Fraction Collectors overcome the past barriers to wide acceptance of SFC and enable chemists to take advantage of the many inherent benefits of SFC:

• High speed separations
• Faster drying of fractions
• Large fraction capacity yields higher fraction resolution and purity
• Higher sample loading
• Orthogonal selectivity to HPLC
• Environmentally friendly/minimal use of organic solvents
• Reduced reagent/disposal costs

Enabling SFC Solutions

The CFC Fraction Collectors allow broad polarity fractionation by SFC into an array of up to 24 fraction containers with high recovery at atmospheric pressure. This convenience and capability simplifies the migration of traditional HPLC applications to SFC for complex mixtures requiring many fractions or multiple samples requiring only a few fractions each.

Applications include:

High purity chiral separations
Chiral compounds are a common artifact in medicinal and other synthetic chemistry. The retention tuning attributes of SFC drive its application to these particularly difficult purifications of chiral compounds─both intermediates and final products─ for a wide variety of chemotypes. Typically, chemists have barely enough fraction capacity to collect the two enantiomers following the SFC separation. Ideally, three fraction cuts should be made of each chiral peak. With the high fraction counts of the CFC Fraction Collectors, chiral chemists can now use SFC as a high throughput purification tool. For example, in a purification of 4 enantiomeric mixtures, the CFC-2 enables collection of six fractions each before taking time to replace a new set of test tubes, thus speeding the medicinal chemistry process.

Isolation of impurities from reaction products
During drug development, analytical procedures are required for the detection and quantitation of degradation and reaction products. Analytical methods are designed to reveal impurities and degradation compounds in the drug product. The resolution of SFC has proven useful in isolating these impurities and the CFC's ability to conveniently collect up to 24 fractions increases the productivity of SFC in this fraction-intensive area.

Fractionation of natural products and other complex mixtures
In working with natural products and other complex mixtures, preparative SFC has demonstrated superior speed and sample loading for the pre-screening purification of drug like molecules. By greatly reducing the variety of compounds in a potential screening sample and perhaps even beginning to accumulate some characteristic data about individual fractions, correlations among hit samples become more apparent earlier in the screening campaign. The CFC instruments bring the convenience and familiarity of HPLC fractionation to the enticing productivity gains and economies offered by SFC.

Isolation of metabolites and biomarkers from biological fluids
The emerging fields of metabonomics and metabolomics are rapidly gaining widespread use in the pharmaceutical, healthcare, and agrochemical industries. Metabonomics enables the rapid identification of endogenous metabolites and biomarkers in various biofluids as a result of a disease state, toxicity, genetic modification, or environmental factors. SFC has demonstrated better separation efficiency and less solvent consumption than conventional approaches, but has not gained widespread adoption due to the limitations of fraction collection. The CFC instruments overcome these prior limitations of low numbers of fractions and time consuming collection container washing protocols designed to prevent cross contamination.

Flash SFC
Flash liquid chromatography (Flash LC) has proven to be a useful technique for the rapid separation and clean-up of excess reactants and reaction products in synthetic organic chemistry, particularly in medicinal chemistry departments of the pharmaceutical industry. Due to the limitations and complexity of collecting fractions with SFC, the concept of a quick and effective clean-up tool using supercritical CO₂ has not been feasible. However, with the CFC instruments, Flash SFC becomes a viable concept, offering inherent speed, resolution, and loading capabilities, in addition to greatly reduced organic solvent consumption and virtually dry fractions immediately following the Flash clean-up step.