It is an extensively used method of column chromatography for qualitative and quantitative analysis of complex mixtures of volatile substances that can be vaporized without decomposition. It was initially proposed by Martin and Synge in 1941 and later in 1952 developed by Martin and James for the separation of volatile fatty acids. Today it is of wide applicability in the analysis of a vast array of organic and inorganic compounds in complex mixtures.

Compound separation in GC is effected between a liquid stationary phase and a mobile gaseous phase. Highly sophisticated, fully automated instruments are available for routine analysis of scores of compounds.

In conventional GLC, columns of glass or metal, either straight or coiled, variable in length from 1–20 m of about 5 mm internal diameter, are coated internally with an inert material of uniform and small particle size to give a relatively larger surface area. Stationary phase liquids such as silicone oils, paraffin, apiezon oils, high boiling point alcohols and their esters, propylene glycols, etc., are dispersed over the stationary phase. Special columns, which serve the double purpose of both support and stationary phase such as cross-linked styrene-like polymers, are also used. Nowadays capillary columns of fused silica of bore diameter varying from 0.15–0.5 mm with column length up to 60 m, either directly coated with stationary phase or with a support holding the stationary phase are used for speeding up analysis and for better resolution.

Mobile phase is an inert gas such as helium, hydrogen, nitrogen, or argon. Compound separation is determined by the flow rate of the gas (ranging from 10–50 ml/min).

The whole arrangement of the column is such that it is heated to provide suitable operating temperatures, which could vary from 150–400°C for different types of compounds. Sophisticated GCs could be programmed to achieve a gradient temperature rise. This enables better separation of different classes of compounds, in a single run without the need for long waiting period for the elution of strongly retained compounds.

The sample dissolved in a volatile solvent like ether in volumes as small as 1 µl is injected into the column. The compounds present in the mixture volatilize as soon as they come in contact with the stationary phase (at the temperature of the column) and get swept across the column by the gaseous mobile phase. Based on their relative partitioning between the stationary liquid phase and the mobile gaseous phase, the volatilized compounds are carried across the column and out of it, by the gas, separated from one another. Hence, they elute out of the column at different time intervals and could be detected by a range of detectors used along with GLCs. These detectors, detect and measure the compounds eluting out based on a property that is characteristic for the compound or by measuring an altered property of the effluent gas due to the compound being admixed with it.

Whatever the property measured, detectors record the presence of the compound in terms of the volume of carrier gas required to elute it or as retention time, that is, the time taken for the sample to elute out since being injected. GC detectors are mostly of flame ionization or electron capture type. The variables that can be controlled to bring about effective separation are the stationary phase and the operating temperature. This is in accordance with the temperature of volatilization of compounds. Volatile oils require 150–300°C, steroids require 250°C, and pesticides require 400°C, and so on. Even nonvolatile compounds such as sugars, flavonoids, cardio active glycosides, etc., may be converted into volatile trimethyl siloxy derivatives or as volatile methyl esters (nonvolatile plant acids). These can then be injected into the column and thus separated and detected.

GC is an efficient tool for qualitative detection and reference compounds co-injected with mixture to be resolved, aid in the quicker identification of mixture components. For quantitative analysis, area of the peak recording the presence of the compound on the chromatogram is measured and it is proportional to the quantity that is present in the mixture.

Tentative compound identification may be effected without reference compounds on a GC coupled to MS. This high-end scientific instrument measures the mass spectra of the compound eluting out of GC. The ion fragmentation data of MS is matched against a library of data on known compounds, providing clues on the nature of the compound. Known compounds are identified by an exact match of data, while for unknown compounds, the fragmentation patterns provide clues to its structural features.

Though used routinely for analytical work, larger preparative columns (approximately 60 m in length, 1–2 cm in diameter) can be used for preparative separation of larger quantities (up to 20 ml) of mixtures.

GC is widely used for routine analysis of volatile oils, plant acids, opium, tobacco, tropane alkaloids, cannabis resin, sapogenins, cardiac glycosides, cocaine and its metabolites in body fluids, pesticide residue estimation, etc.