If you are a fan of the TV Show CSI, then you are familiar with the frequently mentioned Gas Chromatograph (GC) testing.  The show emphasizes its ease of use; put in a sample and a few moments later everything about it is revealed. Not meaning to be the bearer of bad news, but in reality, nothing could be further from the truth. The GC is a highly complex instrument that is commonly used in analytical chemistry for separating and analyzing compounds that can be vaporized without decomposition. In the world of pharmaceuticals, it is routinely used for testing the purity of a particle substance (assay) or for separating the various components of a compound to determine the overall structure or makeup of the substance under test. In this article, we will review the basic operation of the GC instrument in order to develop a better understanding (or review) of this commonly used test method.

GC Analysis relies on two phases of operation. The first phase is the mobile phase, or “moving phase”, in which  an inert or unreactive gas “such as helium or nitrogen” acts as a carrier. The second part is the stationary phase, which refers to a microscopic layer of liquid or polymer on the inside of an inert piece of glass or metal tubing called a column. When the gaseous compounds being tested interact with the walls of the column, this causes each compound in the sample under test to elute at a different times. This is known as the retention time of the compound. It is the comparison of retention times of the materials under test that give the GC its analytical usefulness.

Gas chromatography is “in principle” similar to column chromatography (as well as other forms of chromatography, such as HPLC, TLC), but has several notable differences. First, the process of separating the compounds in a mixture is carried out between a liquid stationary phase and a gas mobile phase. In column chromatography, the stationary phase is a solid and the mobile phase is a liquid. Second, the column through which the gas phase passes is located in an oven, where the temperature of the gas can be controlled. In column chromatography, there is typically no such temperature control. Finally, the concentration of a compound in the gas phase is solely a function of the vapor pressure of the gas.

GC testing has come a long way since a Russian scientist first discovered it in 1903. In today’s modern laboratory, a GC will have many components. One componenet, the inlet, is attached to the column head and provides the means for sample injection into the continuous flow of the carrier gas. Common types of inlets include the split / split-less, which uses a syringe and septum, an on-column inlet, which enables the sample to be directly injected into the column, and the Purge & Trap system, which uses an inert gas that is bubbled through an aqueous sample causing the chemicals to be purged.

Another key component of today’s modern GC systems is the detector. The most commonly used detectors are the flame ionization detector (FID) and the thermal conductivity detector (TCD). Both types of detectors are sensitive to a wide range of compounds, and both work over a wide range of concentrations. While TCDs are essentially universal, FIDs are sensitive primarily to hydrocarbons, more so than a TCD. However, an FID cannot detect water. Both detectors are also quite robust. To compensate for the respective advantages and disadvantages of each detector, they may be run in tandem. Since a TCD is non-destructive to the sample, it can be operated in-series before the destructive FID, thus providing complementary detection of the same sample.

The final section for basic understanding of GC testing is the method. The method is the collection of conditions in which the GC operates for a given analysis. Method development is the process of determining what conditions are adequate and/or ideal for the analysis required. Conditions that can be optimized to accommodate a required analysis include inlet temperature, detector temperature, column temperature and temperature program, carrier gas and carrier gas flow rates, the column’s stationary phase, diameter and length, inlet type and flow rates, sample size and injection technique. Depending on the detector(s) (see above) installed on the GC, there may be a number of detector conditions that can also be optimized.

Use of the GC for quality control testing of materials is a common regulatory requirement. The United States Pharmacopeia makes a multitude of references to this testing as it relates to items currently monographed. In addition, the USP can supply the relevant reference standard needed for this type of analysis.

While this article will in no way make you an expert in GC testing, hopefully it conveys some key points that provide a better understanding of how these complex instruments can assist you in meeting your quality control testing needs.