Applied Technology

Production Scale Chromatography for Purification of Cannabis Extracts

Lance Griffin
Written by Lance Griffin

Chromatography refers to the physical separation of compounds between a stationary phase (solid or liquid) and a mobile phase (liquid or gas). [1] It is commonly used to isolate compounds of interest from complex matrices (such as botanicals). [1]

Analytical laboratories widely use gas chromatography and high performance liquid chromatography to analyze cannabinoid, terpene, and contaminant content in cannabis samples. [2-4] But chromatography is also taking the stage for a different purpose: the isolation and purification of cannabis compounds for scaled production.

Consumers — especially patients — may require precise, standardized, and targeted ratios of phytochemicals. Distillation refines extracts to typically around 80% purity or higher, but certain types of chromatography may provide more efficient and complete results. In fact, chromatography is often used to remediate hemp-based distillates that exceed delta-9-tetrahydrocannabinol (THC) legal limits, and contaminated concentrates.

Centrifugal Partition Chromatography

Centrifugal partition chromatography (CPC) is liquid-liquid chromatography with one liquid phase made stationary by centrifugal force from rotation. [5] Hazekamp et al [5] report that “[CPC] has a very high capacity because of the large volume of stationary phase involved in the separation process.”

Gilson® manufactures CPC instruments for production purposes and points out that CPC is a one-step process and does not require silica, which can cause absorption and must be replaced over time (though silica may be recycled with washing and thermal treatment [6]). The company RotaChrom claims to offer the “largest centrifugal partition chromatographic instrument in the world,” purportedly capable of five hundred kilograms of purified product per month.

Supercritical Fluid Chromatography

Supercritical fluid chromatography (SFC) uses a gas in its supercritical state, most commonly supercritical carbon dioxide (sCO2), for the mobile phase, retaining a conventional solid stationary phase (e.g., functionalized silica). Hoffstetter et al [7] maintain that contemporary industrial SFC is the result of “five decades of continual refinement since the first report on high-pressure gas chromatography in 1962,” and that in contemporary times, it stands as the “method of choice for chiral and semi-preparative applications in pharmaceutical, cosmetic, and food-related technologies.”

Certified cGMP hemp toll processor and manufacturer Thar Process utilizes sCO2 for large-scale extraction and chromatography purification. Advantages of SCO2, according to the company, include low viscosity, high diffusivity, and strong sustainability. Thar Process cites capabilities of up to 99.9% purity of single cannabinoids from SFC fractionation equipment. Their industrial scale instruments may be capable of processing up to 80 kg of distillate per day (24 hours).

Flash Chromatography & Reversed-Phase Chromatography

Flash chromatography pushes (with pressure) the mobile phase through the solid stationary phase to speed up the overall process. It is suited for the quick separation of compounds with distinct polarities. Reversed-phase chromatography inverts the polarities of the mobile and solid phases to first elute hydrophilic molecules. This latter technique is more suited to the separation of molecules with similar polarities, such as THC and CBD. Honey Gold Processing advertises THC remediation for up to 500 liters of distillate (2-4% THC) using reversed-phase chromatography.

Simulated Moving Bed Chromatography

Simulated moving bed (SMB) chromatography uses a system of multiple solid columns engineered in a circular series of zones with inlets and outlets. The liquid mobile phase then courses through the column zones at controlled rates. [8] This technique is limited to binary fractionation. SMB chromatography dates to the 1950s and may be the most economical route to scaled production. GMI manufactures an SMB instrument they report capable of 1,000 kg of purified product per year.

Chromatography thus represents a powerful tool for cannabis producers, affording the isolation of cannabinoids and other chemicals with unparalleled precision. The implications of these instruments at scale are significant for product design, quality control, analytical testing compliance, and research and development.

References

  1. Hage, David S. “1 – Chromatography.” Principles and Applications of Clinical Mass Spectrometry: Small Molecules, Peptides, and Pathogens. Edited by Nader Rifai et al., Elsevier, 2018, pp. 1–32, doi:https://doi.org/10.1016/B978-0-12-816063-3.00001-3.
  2. Nie B, et al. “The Role of Mass Spectrometry in the Cannabis Industry.” Am. Soc. Mass Spectrom, vol.30, no.719, 2019, Y730. Journal Impact Factor = 3.202, Times Cited = 3
  3. Zivovinovic S, et al.“Determination of Cannabinoids in Cannabis sativa Samples for Recreational, Medical, and Forensic Purposes by Reversed-Phase Liquid Chromatography-Ultraviolet Detection.” J Anal Sci Technol, vol.9, no.27, 2018, https://doi.org/10.1186/s40543-018-0159-8. Journal Impact Factor = 1.519, Times Cited = 5
  4. Klein RFX. “Analysis of Marijuana by Liquid Chromatographic Techniques: A Literature Survey, 1990 – 2015.” Microgram Journal, vol. 12, no. 1-4, 2015.
  5. Hazekamp A, et al. “Preparative Isolation of Cannabinoids from Cannabis sativa by Centrifugal Partition Chromatography.” Journal of Liquid Chromatography & Related Technologies, vol.27, no.15, 2004, pp. 2421–2439. Journal Impact Factor = 0.987, Times Cited = 49
  6. Wahshi FS, et al. “Our Experience of Using Thermally Recycled Silica Gel in a Teaching and Small Research Laboratory Setting.” Proceedings, vol.9, no.28, 2018. Journal Impact Factor = 2.690, Times Cited = 1
  7. Hofstetter RK, et al. “Supercritical Fluid Chromatography: From Science Fiction to Scientific Fact.” ChemTexts, vol.5, no.13, 2019.
  8. Juza M, et al. “Simulated Moving Bed Chromatography and Its Application to Chirotechnology.” Trends in Biotechnology, vol. 18, 2000, pp. 108–18, doi:10.1016/S0167-7799(99)01419-5. Journal Impact Factor = 13.747, Times Cited = 285

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Lance Griffin

Lance Griffin

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