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Supercritical CO2 Chromatography: Remediating Extracts and the Planet in Tandem

Some folks busy themselves by debating climate change and carbon dioxide’s role in our postulated impending doom. Others have evolved to trying to mitigate said doom in innovative ways. Here comes the cannabis industry and the demand for sustainable, environmentally-sound manufacturing process augments, giving carbon dioxide another chance, literally, through recycling waste gas generated by other industries.

You know all about supercritical carbon dioxide (sCO2) if you’ve been frequenting Extraction Magazine blogs or the print/digital magazine. Cannabis concentrates produced with CO2 abound, as many product designers like the non-toxic, inflammable attributes of repurposing this greenhouse gas for more constructive, or rather, deconstructive, purposes.

There’s another use of sCO2, however. Once the crude extract is isolated, its phytoconstituents can be further fractionated using supercritical fluid chromatography, or SFC. SFC is analogous to normal phase high-performance liquid chromatography (LC) in several regards, such as the use of a non-polar mobile phase, the instrumentation used for separating chemical species, and detection schemes for identifying and quantifying individual analytes. And just like in LC, a liquid sample is injected into a pressurized column where molecules interact with column packing materials, like bare silica, to differing levels than their molecular brethren, enabling the separation of chemicals.

SFC utilizes a supercritical gas, most often CO2, instead of a liquid mobile phase to perform the separation. This means that the entire separatory column must be pressurized, and that the pressure inside must be monitored and regulated to ensure that the conditions required for reaching the supercritical point are retained.

As mentioned before, CO2 is a non-polar solvent, and thus, is good at extracting molecules of comparable polarities. If an analyte can be dissolved in methanol or less polar solvent, it’s considered to be an adequate candidate for SFC. [1] To enable the extraction of more polar species, often a co-solvent like ethanol can be used with the CO2. I don’t want to go all van Deemter on you, so, suffice to say for now that the addition of a co-solvent changes the properties of the solvent, and so, while pure CO2 would provide about 10 to 15 times the speed, SFC is more commonly said to be 3 to 5 times faster than LC using the same instrumental parameters.

SFC is often used for separating chiral compounds, which are those molecules, like enantiomers, that have mirror-images that cannot be superimposed. Often in pharmaceutical manufacturing, racemic mixtures are produced, which contain a 50/50 mix of left- and right-handed isomers. The problem with this is that while one hand might be a benevolent benefactor of well-being, the other hand can be adversarial, causing undesirable effects. Enantiomerically pure drugs can be re-patented, replacing the old, racemic form, allowing a company to stretch out their patent a bit longer.

And now, for the relevance to Cannabis sativa. You’ve produced your crude extract and have winterized to strip out molecules like chlorophyll and plant waxes. You’ve decarbed the oil and have done some other refining to permit that oil to really pop with translucency. But alas, this is an extract of hemp, and your delta-9 tetrahydrocannabinol (THC) levels are above the 0.3% cutoff. You could try converting THC to CBN, but you don’t want to do anything too sacrificial to the rest of the desired components of the extract. This is the time for selectivity, and SFC can provide the answer.

Perhaps you’re the mirror image of the person being described in the preceding paragraph… the one with the THC problem. You don’t have a dark side like a racemic drug, so THC is your holy grail. The thing is, you’ve seen the promised land and understand that for your business, you want to thrive on formulations that contain beneficial molecules other than just THC. You don’t want every product to be full-spectrum, however. Rather, you’d like to isolate the extracted cannabinoids and then recombine those desired in precise ratios for generating reproducible consumer experiences. By knowing where each analyte elutes, you can capture these desired eluting fractions. And thus, your secret sauce is born.

Or, more direly, perhaps you’ve got an extract that requires remediation of a contaminant, like myclobutanil. SFC can help you fractionate what’s good, while getting rid of what’s bad, especially in complex mixtures, like the mother liquors resultant from the crystallization processes used in making CBD isolate.

As the blossoming belief in the medicinal capacity of C. sativa fully blooms on a worldwide scale, our ability to respect the Earth upon which our plants thrive will be monumentous. Finding additional uses for villainous CO2, like SFC, where it can personify the hero for a change, presents an exciting option for staying true to homeostatic ideals.


[1] Kot, A., Sandra, P., Venema, A. “Subcritical and Supercritical Fluid Chromatography on Packed-Columns- A Versatile Tool for the Enantioselective Separation of Basic and Acidic Drugs.” J. Chromatogr. Sci., vol. 32, no. 10, 1994,  pp. 439–448. [journal impact factor = 1.216; cited by 63]

Image Credit: TharProcess

About the author

Jason S. Lupoi, Ph.D.