GURU NANAK INSTITUTE OF PHARMACEUTICAL SCIENCE AND
TECHNOLOGY (AnAutonomous Institute)
TOPIC- FLASH CHROMATOGRAPHY
NAME OF THE STUDENT:MOHAMMAD JAVED
PNR NUMBER:186112201008
ACADEMIC SESSION:2022-23
PAPER NAME:ADVANCE SPECTRALANALYSIS
PAPER CODE:MPT 2031
Affiliated to MaulanaAbul KalamAzad University of Technology

TABLE OF CONTENT
1.INTRODUCTION
2.PRINCIPLE
3.COLOUMN CHROMATOGRAPHY(BRIEF)
4.INSTRUMENTATION
5.COLOUMN CHROMATOGRAPHY Vs FLASH CHROMATOGRAPHY
6.WORKING
7.ADVANTAGE AND DISADVANTAGE
8.APPLICATIONS
9.CONCLUSION
10.REFERENCE

INTRODUCTION
 Flash chromatography was discovered in 1978 by W. Clark Still in
Columbia University.
 Flash chromatography is advanced version of column chromatography.[1]
 Flash chromatography is also called medium pressure chromatography.

PRINCIPLE OF FLASH CHROMATOGRAPHY
 Chromatography exploits the differences in
partitioning behavior between a mobile phase
and a stationary phase to separate the
components in a mixture. In flash
chromatography gas-pressurized solvent
reservoir is used to accelerate solvent flow and
achieve superior chemical separations in less
time than traditional gravity-based column
chromatography.[2][3]

COLOUMN CHROMATOGRAPHY(THE CONVENTIONAL)
 In column chromatography a crude reaction mixture is
applied on top of a bed of silica gel loaded in a glass
column.
 A gravity-fed solvent mixture (mobile phase) passes
through the vertical column of silica gel (stationary
phase), separating the individual products of the crude
reaction mixture.[4]

INSTRUMENTATION
Selection of Stationary Phase
a.Silica: Slightly acidic medium. Best for ordinary compounds, good
separation is achieved.
b.Alumina: Basic or neutral medium. Can be effective for easy separations,
and purification of amines.
c.Reverse phase silica: The most polar compounds elute fastest, the most
nonpolar slowest.[1]

Selection of Solvent Systems
Flash column chromatography is usually carried out with a mixture of two solvents, with a polar and a
nonpolar component. Though one solvent can also be used. Some examples of one component systems
are:
a.Hydrocarbons: pentane, petroleum ether, hexanes. (Least Polar)
b.Ether and dichloromethane (very similar polarity). (Moderately Polar)
c.Ethyl acetate. (Most Polar) [1][2]
Mobile Phase
According to type of eluent:
a.Gradient: Composition of solvent changes throughout the run. It is used for multiple components.
b.Isocratic: Solvent has same composition throughout the run. It is used for single component.

 Pump : A pressure range up to either 10 bar or 50 bar gives
optimum separation results for a broad range of applications.
There are different types of pumps:
i. Pump Module C-601, 10 bar: The Pump Controller C-610 with
a Pump Module C-601 is used for fast isocratic flash
separations.
ii. Pump Module C-605, 50 bar: The Pump Manager C-615 with a
Pump Module C-601/C-605 is used for isocratic Flash
separations.
iii. Pump Manager C-615 : The Pump Manager C-615 with two
Pump Modules C-601/C-605 for binary solvent gradients.
iv. Vacuum Pump/peristaltic Pump: Transfer Solvent from Mobile
phase Reservoir to Flash Pump.[3]

Columns
i. Glass Columns : A wide range of columns offer maximum
flexibility for every situation. Depending on the nature and
the quantity of the sample offers a series of column types
which vary in form, size and performance.
ii. Plastic+Glass Column: Plastic+ Glass-coated Glass
Columns are available for larger sample amounts and
higher pressure applications on a high safety level.
iii. Precolumns: Precolumn are minimizing dead volumes and
enhance the life time of the main column by trapping
contaminants. The small Precolumn, fits to glass
columns.[2][3]

Sample Loading: Two different methods are used to load
the column: the wet method and the dry method.
 Wet Loading Method: In the wet method, the sample to
be purified (or separated into components) is dissolved in
a small amount of solvent, such as hexanes, acetone, or
other solvent. This solution is loaded onto the column.
 Dry Loading Method: First dissolve the sample to be
analyzed in the minimum amount of solvent and add
about 100 mg of silica gel. Swirl the mixture until the
solvent evaporates and only a dry powder remains. Place
the dry powder on a folded piece of weighing paper and
transfer it to the top of the prepared column.[2][3]

MAJOR DIFFERENCE BETWEEN COLUMN AND FLASH CHROMATOGRAPHY

PARAMETERS COLOUMN
CHROMATOGRAPHY
FLASH
CHROMATOGRAPHY
1.Separation Separation is due to
gravity.
Pressurized gas is used to
accelerate separation and
achieve superior chemical
separations.
2.Time Separation is slow. Separation is fast
3.Particle size Silica gel particles of size
74-250 µm (60-200 mesh
size) is used.
Silica gel particles of size
40-63 µm (230-400 mesh
size) is used.
4.Sample size Used for large sample size Used for small sample size
5.Cost Less expensive then flash Very expensive

WORKING
 The column is clamped vertically, and the sample is
introduced to the top of the sand/silica before more
mobile phase is added. Compressed air or nitrogen is
then used to move the solvent through the column.
As in gas or liquid chromatography, compounds with
a greater affinity for the solid phase move more
slowly through the column allowing different
fractions to be collected from the column. These can
then be identified using NMR or by another
technique.[2][1]

ADVANTAGE AND DISADVANTAGE OF FLASH CHROMATOGRAPHY
 Advantages:
 Quick and efficient separation technique
 Can be used for a wide range of sample sizes and types
 Easy to use and relatively low cost
 Can be automated for high-throughput purification
 Disadvantages:
 Limited resolution compared to other separation techniques such as HPLC
 The use of large amounts of solvent can be wasteful and environmentally harmful
 The stationary phase can be expensive and difficult to recycle.

SOME MAJOR APPLICATIONS
•Flash chromatography is commonly used in the purification of organic compounds in various fields
such as:
 Pharmaceuticals: for the isolation of drug candidates and intermediates
 Biotechnology: for the purification of proteins and peptides
 Natural product chemistry: for the isolation of natural products from plants and microorganisms
•Other applications include food and beverage analysis, environmental analysis, and forensic analysis.[5]

CONCLUSION
 Flash chromatography is a widely used separation technique that offers quick and efficient
purification of organic compounds.
 It is versatile and can be used in various fields such as pharmaceuticals, biotechnology, and
natural product chemistry.
 While flash chromatography has some disadvantages, its advantages make it a valuable tool for
many researchers and scientists.

REFERENCE
1. A. B. Roge et al.,; BRIEF REVIEW ON: FLASH CHROMATOGRAPHY; International
Journal of Pharmaceutical Sciences and Research Vol. 2, Issue 8; 2011; Page: 1930-1937.
2. W.C Still, M Kahn , A Mitra, Flash chromatography, J.Org.Chem. 43(14); 1978; Page: 2923-
2925.
3. Cudiamat, G. (2020, November 13). Flash Chromatography. Chromatography Online.
https://www.chromatographyonline.com/view/flash-chromatography-3.
4. Regenstein, J. M., & Regenstein, C. E. (1984). Column Chromatography. Food Protein Chemistry,
144–167. https://doi.org/10.1016/b978-0-12-585820-5.50020-8
5. FLASH CHROMATOGRAPHY: AREA & APPLICATIONS. (n.d.). PharmaTutor.
https://www.pharmatutor.org/articles/flash-chromatography-area-applications.