High-Performance Liquid Chromatography vs. Flash Chromatography for THC Remediation

Blog, Chromatography

CBD chromatography has matured and developed over the last several years. Flash chromatography is a key technique used for hemp remediation. The following discusses the pros and cons of flash column chromatography when compared to high pressure liquid chromatography.

What is Flash Column Chromatography?

Flash column chromatography also known as flash chromatography is used extensively to separate and prepare pure amounts of components that comprise a liquid mixture. Many companies use flash chromatography who separate out CBD from THC so that their hemp extracts will be fit for commerce. This is known as THC remediation. There are several benefits and advantages that high-performance liquid chromatography equipment has over flash column chromatography equipment. These include the following:

  • High efficiency

  • Shorter run times

  • Less solvent usage

  • Peak Shape

  • Better recovery

  • Better scale up

  • Lower cost of operation

scientist using chromatography equipment

HPLC Efficiency; Higher Than Flash Chromatography

Flash chromatography columns are typically packed with non-spherical particles that have a large particle diameter distribution. This particle size distribution typically is in the range of 30 to 60 microns. As a consequence, flash columns are typically very inefficient and do not have the resolving power of a high performance liquid chromatography machine.

Shorter Run Times & Less Solvent Usage

In order to compensate for their inefficiency, typically flash chromatography columns will be much longer in order to obtain the number of plates needed for the separation. This leads to longer run times compared to high-performance liquid chromatography. The longer run time is primarily due to the fact that the minimum volume to get a compound out of the column for a flash chromatography column is much greater compared to high-performance liquid chromatography.

High Cost of Solvent with Flash Column Chromatography

A key contributor to the overall cost of running a flash chromatography system is the solvent usage itself. Typically a flash chromatography would have to purchase large amounts of solvents due to the high solvent usage and have a legal place to store all those solvents. The following lists the important considerations for solvent operating cost:  

  • The cost of solvent startup

  • The cost of solvent re-use

  • The cost of solvent loss

lab testing vials for chromatography

Flash Chromatography Equipment and Facilities Fire and Electrical Code Requirements

Any piece of equipment that is used in a production setting must be UL-listed and must also comply with NFPA requirements for solvent storage, room classification, electrical installation and solvent transfers. There are many requirements for the lawful installation of equipment that uses flammable solvents. Primary requirement is that the equipment itself be certified to be compliant with the requirements of class 1 division 2 electrical requirements for the NFPA electrical code 70. Class 1 division 2 installations and equipment take into account the possibility of leaks from the equipment and the fire hazard that are associated with those leaks. Any centrifugal partition chromatography system must address class 1 division 2 requirements.

Peak Shape

An ideal peak shape for a perfectly packed column is a Gaussian peak. Sometimes the peak can be skewed on the leading edge of the peak or on the trailing edge of the peak due to method conditions.

When the back of the peak is skewed, it looks like it has a tail. This tail is caused by many different factors including secondary chemical interactions or a large extra column volume relative to the column.

peak shape graph

Fronting of the peak is typically caused by overloading the column.
High-performance liquid chromatography columns typically are typically more efficient and have less peak volume than observed with flash chromatography.

That’s why it is important for any high-performance liquid chromatography equipment to eliminate extra-column volume and reduce or eliminate unnecessary causes of liquid mixing. This requirement is a lot less stringent with flash chromatography simply because the column volumes are so large.

Packing quality of a chromatography column is also a large contributor to the presence of a tail. In the case of flash chromatography, the packing quality is rather poor due to the non-spherical and randomized particle diameter that are used in flash column chromatography.

Due to this factor, high-performance liquid chromatography columns and systems that have been engineered to match those columns, typically have a better Peak shape than flash chromatography machines.

Recovery of Sample

When a sample gets injected on a column, the sample starts to interact with the stationary phase. The components that the chromatographer desires to separate, interact with the stationary phase differently. Colored laboratory vialsFor example, one component of the sample will associate more with the mobile phase and elute from the column first. Another component may interact more strongly with the stationary phase and elute from the column later than the first component. As long as each component interacts weakly with the stationary phase so that it moves on the column, high recovery is certain. This is the case with the separation of THC and CBD. It is possible to devise a method whereby zero recovery is obtainable by changing the stationary phase to a highly retentive phase or by changing the mobile phase. Of course, those methods would never be practical.

Column Reconditioning

In some cases some components of the sample may interact with the stationary phase so strongly that they never elute. These components may stay in or even be bound to the stationary phase and interfere with the stationary phase’s ability to separate out the desired compounds. This situation can be remedied by washing the stationary phase in a strong solvent that will preferentially dissolve the strongly interacting components of the sample. This is known as reconditioning the column and can be automated into a method sequence.

Scale Up and Operating Costs

High-performance liquid chromatography is better for scale up simply due to the fact that the columns are more efficient and use less solvent. The column material must also be considered as a factor in operating cost.

Why pure99 HPLC is Superior to Flash Chromatography

Chromatography has become critically important for the widely popular formulations of CBD products including full-spectrum, broad-spectrum, and CBD isolate – all of which are increasingly desired in the growing hemp extract markets. With the ability to selectively manipulate various cannabinoids, terpenes and other materials from the plant matrix, there are a number of methods by which chromatography can be accomplished, but HPLC and extraktLAB’s pure99 have proven themselves to be advantageous for an number of reasons in larger scale extraction. pure99 chromatography All in all, the pure99 high performance liquid chromatography system is advantageous in terms of cost, run time, and overall efficiency when compared to traditional flash column chromatography equipment. With a max flow rate of 4 – 8 LPM and a solvent recycling rate of 3.6 – 7.2 LPH, it is a highly efficient, scalable chromatography solution for any extraction business looking to take their production to a new level.



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Dr. Thompson is a separations scientist, entrepreneur, and inventor. As a scientist, he has a strong technical background and industry experience in analytical instrumentation, in-vitro diagnostics, biotech, mining, and homeland security markets.

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