Flash Chromatography

Flash chromatography has become a critical part of the hemp and cannabis extraction industry. Because of its ability to identify and separate various components efficiently, flash chromatography is essential for testing, identification and remediation of any hemp or cannabis extract.

In this article, we will examine the benefits of flash chromatography and how it can benefit your extraction operation. The beginning of this article will explain what chromatography is, and where it is used.

Then we will look at the difference between high-performance liquid chromatography (HPLC) and flash chromatography which are both commonly used in the extraction industry. Finally, we will discuss the advantages of flash chromatography in the extraction industry and how you will benefit from having a flash chromatography system in your process.

What is Flash Column Chromatography

Let’s define what flash chromatography is and why it is useful today. Flash chromatography is simply a method of chemical separation used to purify chemical mixtures. Because of this, it is also commonly referred to as flash purification. This is very useful for isolating specific natural components in a product.

Flash chromatography is a form of liquid chromatography that uses a solvent coupled with a pressurized gas like nitrogen in order to aid in the separation process. Then, a solid silica material is often used to fill a column and used as the stationary phase. By adding the solution to the mobile phase, the materials in need of testing or remediation will pass through the column and the separation process will be complete.

Flash chromatography has become a necessity for purification in order to make unadulterated products. A good example of this is in the synthesis of molecules. When synthesis is performed, unreacted materials in a solution can create undesirable byproducts during the synthesis process. In order to avoid those byproducts, flash chromatography can be used to remediate those unreacted materials.

scientist using chromatography equipment

How Does Flash Column Chromatography Work?

Now that we’ve talked about what flash chromatography is, and where it is used, let’s take a look at how it works. The basic principle of flash chromatography is based on the solubility of a particular compound in a particular solvent. So, compounds with a lower solubility in the solvent used are more readily able to be separated and collected due to their affinity to the material used in the stationary phase. Let’s take a closer look at the process itself.

As the name would suggest, flash column chromatography uses a vessel called a column filled with a medium like silica to be used as the stationary phase. This column is where the solution being separated has been introduced into the liquid used as the mobile phase. During the flash chromatography process, the solution inside of the mobile phase will pass through the column filled with the stationary phase using a vacuum pump.

As the liquid mobile phase passes through the stationary phase, the materials in the desired solution with the highest mobility will pass through the stationary phase at the highest rate while the materials with the lowest solubility will pass through more slowly. This allows the selected materials with the lower solubility to be selectively separated and captured so that they can be removed from the solution.

Due to the efficiency of flash chromatography, it is an incredibly useful technique for separations in the hemp and cannabis industry. This can apply to intentional remediation of cannabinoids like THC in order to remain legally compliant with federal CBD product standards, or for finding and removing other potentially harmful compounds like pesticides, heavy metals and solvents.

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Cannabinoid Separation Using Flash Chromatography

When it comes to hemp and cannabis specifically, flash chromatography is an incredibly useful tool for separating cannabinoids and other plant compounds so that they can be isolated for product formulation. Let’s briefly walk through the isolation process of cannabinoids using flash chromatography.

The Flash Chromatography Process

  1. Add the extract you intend to separate into an eluent used as the mobile phase. This is often a solvent such as methanol, ethanol or pentane that will efficiently separate the desired cannabinoids during the flash chromatography process. Selectivity of a solvent is an important factor in the separation process meaning that the solvent used will have the desired effect on the intended cannabinoid being separated. Where one solvent may work for one compound, it may be useless for another compound, so solvent choice is very important.
  2. The solvent/extract mixture can be applied to the top of the column containing the stationary phase which is often a silica or gel. While gravity can effectively perform the separation process, it is not very efficient. Therefore, a vacuum pump is often used to pull the mobile phase with the extract through the stationary phase in order to begin the separation process.
  3. As the separation process is underway, you can then elute the separated cannabinoids into separate vessels so that they can be collected for further processing. You can specifically target a particular cannabinoid, or allow for the separation of multiple cannabinoids. However, it is more efficient to select a specific cannabinoid and tailor your process to that separation process.
  4. After the separation process, there is still an amount of solvent left in the separated cannabinoid. It is important to remove that final solvent using some kind of evaporation process like a rotary evaporator or a falling film evaporator. Once this has been accomplished, you should have a full isolated cannabinoid. That said, there should be some necessary testing to ensure that all solvent and traces of other compounds have been removed.
lab testing vials for chromatography

Applications of Flash Column Chromatography

Most of the common applications of flash column chromatography are in the pharmaceutical industry. In this industry, flash chromatography can be used for antibiotic purification, early drug discovery, protein analysis, and sample cleanup among others. There are other areas outside of the pharmaceutical industry that flash chromatography is also very effective including DNA purification, formulation of dietary supplements, creating Biomarkers and more.

The formulation of natural products is also a common application of flash chromatography. For example, common supplements on store shelves like ginkgo biloba, ginseng and green tea extracts are all isolated using methods like flash chromatography to ensure purity and safety. Because there are other compounds in the original plants that could be detrimental to the formulation of the product, flash chromatography is efficient enough in separations to remove those other compounds and create a pure product.

Flash Chromatography in the Hemp Industry

Now, let’s take a look at the hemp and cannabis industry. In the CBD industry, there is a federal mandate that any CBD product be formulated with 0.3% or less delta 9 THC in order for that product to be considered legal. Despite going through rigorous distillation, hemp extracts may still have a THC level that is not legally allowed to be formulated. This is where flash chromatography comes into play.

By using this method of chromatography, a processor can effectively, measurably remediate THC from a final extract to a specific amount of THC that is at or below that 0.3% threshold. This can also be applied to specifically formulate products to have exact quantities of certain cannabinoids in a final product which has become more desirable as interest in novel cannabinoids increases.

Looking more broadly at both hemp and cannabis product formulations, the need to remediate other materials from an extract. In order to ensure a safe product, flash chromatography can be used largely to identify and remove materials like heavy metals and pesticides and effectively remove them from a final extract. Because certain materials have a certain affinity for the material used as a stationary phase, they can be effectively separated from the extract while the desired products like CBD, THC, and terpenes can pass through the column and be collected as a safe, potent product.

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Flash Chromatography vs the Prep HPLC Technique

While similar, there is one particular difference between a high-pressure liquid chromatography technique and a flash column chromatography method. Another term for flash chromatography is medium pressure chromatography. The reason for this is that, although the mobile phase is being influenced by a vacuum pump, the amount of pressure being used is not very high. However, compared to an HPLC method, the pressure being applied to the system can reach as high as 5000 psi.

Another difference between the HPLC and flash chromatography is the media particle size. Most HPLC systems will typically pack their columns with a media of 5 to 15 microns in size. This is a good way to improve separations overall, but does have some limitations. The particle size typically used in flash chromatography methods is around 25 to 50 microns. This generally reduces the pressure of operation while increasing flow rates.

How Column Size Affects Chromatography

Another factor is the general dimensions of the columns used for flash chromatography and HPLC systems. The typical size of the columns used in HPLC systems tends to be longer and narrower than that of flash chromatography. The benefits of this in HPLC chromatography can provide an overall better separation. That said, the wider columns used in flash chromatography are more capable of higher sample loads that would otherwise create issues with HPLC systems. The difference between these columns also affects the overall pressure of these systems which is the primary difference between HPLC and flash chromatography systems.

One of the last differences between these two chromatography systems is the cost of the materials needed like columns. Columns used in HPLC chromatography are most often a stainless-steel material in order to handle the higher pressures of that method. Because the flash chromatography method operates at lower pressures, the columns used are made of polypropylene and polyethylene which are much more cost efficient.

Flash vs. HPLC Chromatography Flash Chromatography High-performance liquid chromatography
Pressure Medium pressure High; up to 5000psi
Media particle size 5 to 15 microns 25 to 50 microns
Column size short/wide long/narrow
Cost of materials Low High

How Can Consumers and The Industry Benefit From Flash Chromatography

Because flash chromatography is such a safe and efficient method for testing and separation, it is an incredibly useful tool in the industry of hemp and cannabis extraction. There are a number of reasons why chromatography is necessary in this industry including cannabinoid separation, THC remediation, and testing of materials for quality and safety.

For separation purposes, flash chromatography is highly efficient for product formulation. For example, the popularity of so-called “designer spectrum” products are increasing as the technology to make them has improved. These are products that are formulated with specific levels of cannabinoids and terpenes in order to achieve a desired effect. This is very common in the recreational cannabis extract industry in which products are formulated with exact ratios of THC to CBD as some customers prefer a certain level of each in their chosen product.

Why THC Remediation is so Important

As mentioned above, the need for remediation in CBD products is essential to keep a product legal. Without remediation, levels of THC in a CBD product can reach above the 0.3% legal threshold and render the product useless since it cannot be sold. Flash chromatography is the most effective method to remove THC from a distillate in large enough quantities to make it an efficient process. While there are other ways to separate cannabinoids, this is the most effective and cost efficient in a large scale extraction process.

Perhaps the most important thing that flash chromatography is used for in the extraction industry is testing. There can be a number of different materials in an extract that can disrupt the formulation process, or worse, be harmful to the consumer if not properly removed. Chromatography’s original use was for identifying and testing materials in a solution. When a distillate undergoes flash chromatography, it is capable of testing and removing materials like residual solvents, pesticides, metals, etc. All of which could make an otherwise quality product unusable.


Final Thoughts

It is clear now that chromatography has changed the hemp and cannabis industry for the better and has become a staple in the extraction process. With testing becoming vitally more important to increasingly strict federal regulations, large scale chromatography can be used as the most efficient method to test and remediate extracts to ensure potency and purity. Not only that, chromatography is one of the most effective ways of creating specific extracts with its capability of separating cannabinoids into their individual components for product formulation down the line.

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