Flash column chromatography is a method of chemical separation that is used to purify chemical mixtures. It is also known as flash purification, due to its function as a purification method. It is also sometimes referred to as medium pressure chromatography.
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The technique can be used to isolate a natural component or synthesize a novel molecule. It is relied upon as a simple way of separating molecules from complex mixtures.
How does flash column chromatography work?
The specialized technique utilizes compressed gas, such as air or nitrogen, or, in some cases a pump is used in place of gas, to move a solvent through a column filled with a pure, solid medium. Often synthetic silica is used for this medium onto which the mixture to be separated is introduced.
Once the mixture has been introduced to the top of the column, compounds with a higher solubility move down the column at faster rates than those with lower solubility. Gravity facilitates this movement, with more highly soluble compounds moving downwards faster than the flow of the mixture. This allows for these highly soluble compounds to be collected.
These compounds are always extracted in a purer state than when they were combined within the original mixture. The resultant components emerge from the bottom of the column at different times depending on their rate of diffusion, allowing scientists to separate the components of a mixture based on their solubility.
The method of flash chromatography is essentially a sped-up version of conventional chromatography. The technique can be considered as a hybrid method, combining medium pressure and shorter column chromatography and utilizing air pressure to speed up the process and obtain the resultant compounds in a shorter time frame.
The technique was popularized by Clark Still of Columbia University who adopted the method as an alternative to gravity-fed chromatography, which is often slow and inefficient. Flash column chromatography differs from the older, slower version in that it uses pressurized gas to move the solvent through the column of the stationary phase.
The theory of flash column chromatography
The method of flash column chromatography capitalizes on the innate partitioning behavior differences between the mobile phase and the stationary phase to separate the individual components of a mixture.
The mixtures compounds interact with the stationary phase based on their charge, adsorption, and relative solubility. The measurable speed at which a substance passes through the chromatographic system is known as the retention, which is as the time between injection and detection.
Flash Column Chromatography
The advantages of flash column chromatography
The numerous advantages of flash column chromatography over alternative methods have helped it become a popular technique within a range of disciplines.
Most notably, flash column chromatography overcomes the main drawback of conventional chromatography, which is the slow rate at which the solvent percolates move through the column. Flash chromatography overcomes this with the use of air pressure, which helps to move the solvent through the column at higher speeds, having the impact of significantly reducing the time it the to purify a mixture, resulting in required operation time of just 10-15 minutes to successfully separate a mixture.
In addition to performing separations in drastically shorter time frames, flash column chromatography has several other advantages. It is ideal for separating compounds up to quantities into gram sizes. It is relatively cheap, with no requirement for expensive equipment. The method is also economic, due to its speed of processes mixtures. It is also considered to be an ideal way to transfer results from thin-layer chromatography (TLC) to capillary liquid chromatography (CLC). Finally, the method utilizes low operating pressure and has a simple packing procedure.
These advantages have helped to cement flash column chromatography as a standard analytical and purification method in labs across the globe.
Applications of flash column chromatography
There is a wide range of uses of flash column chromatography, from forensic pathology and crime scene testing to nucleic acid research and food pathology. However, one of the most popular applications of the technique is in the drug discovery process.
Pharmaceutical research frequently utilizes flash column chromatography in the drug discovery process. Scientists often derive chemical compounds with biological activities for novel therapeutic medications from natural sources, such as from animals, plants, and microorganisms. These are referred to as natural products (NPs). Scientists constantly look to NPs when developing new drugs, with roughly half of all pharmaceuticals approved between 1981 and 2006 deriving directly or indirectly from NPs.
The first stage of the development process often involves extracting NPs from their natural source. In most cases, purification of large quantities of the source is required to extract enough of the NP for scientists to experiment with. Flash column chromatography is often relied upon as this purification method for its speed, efficacy, and relatively low operating costs.
The future of flash column chromatography
Flash column chromatography has firmly established itself as an effective and reliable purification method, allowing scientists across several disciplines to extract compounds from mixtures for a variety of purposes. It is likely that, due to its number of benefits, the technique will remain commonplace in labs across industries.
Sources:
- Ahmad Dar, A., Sangwan, P., and Kumar, A., 2019. Chromatography: An important tool for drug discovery. Journal of Separation Science, 43(1), pp.105-119. https://www.onlinelibrary.wiley.com/doi/full/10.1002/jssc.201900656
- Eldridge, G., Vervoort, H., Lee, C., Cremin, P., Williams, C., Hart, S., Goering, M., O'Neil-Johnso, M., and Zeng, L., 2002. High-Throughput Method for the Production and Analysis of Large Natural Product Libraries for Drug Discovery. Analytical Chemistry, 74(16), pp.3963-3971. https://pubs.acs.org/doi/abs/10.1021/ac025534s
- Moosmann, B., Kneisel, S., Wohlfarth, A., Brecht, V., and Auwärter, V., 2012. A fast and inexpensive procedure for the isolation of synthetic cannabinoids from ‘Spice’ products using a flash chromatography system. Analytical and Bioanalytical Chemistry, 405(12), pp.3929-3935. https://link.springer.com/article/10.1007/s00216-012-6462-0
- Price, K., Curl, C., and Fenwick, G., 1987. Flash chromatography—A simple technique of potential value to the food chemist. Food Chemistry, 25(2), pp.145-153. https://www.sciencedirect.com/science/article/abs/pii/030881468790063X
- Williams, T., Riddle, M., Morgan, S., and Brewer, W., 1999. Rapid Gas Chromatographic Analysis of Drugs of Forensic Interest. Journal of Chromatographic Science, 37(6), pp.210-214. https://academic.oup.com/chromsci/article/37/6/210/315771
Further Reading