21 Gas Chromatography

Gas chromatography (GC) is a form of chromatography that uses a gaseous mobile phase. This mobile phase does not solvate analytes and, unlike LC, has no role in determining the retention of analytes. Rather, temperature drives retention and elution as analytes undergo a series of transitions between their vapor state and a condensed state associated with the stationary phase. Elution order is thus determined by both boiling point and interactions with stationary phase. Compounds of similar polarity will tend to elute in order of increasing boiling point.

Instrument Design

The main components of GC instrumentation are the carrier gas cylinder (e.g. N₂, He, Ar), flow regulator (typically 1–2 mL/min), injection system, oven and column, and detector.

Injection. For liquid samples, split/splitless injector designs are most common. In splitless injection, a small amount of sample is injected into a heated port (~50 °C hotter than the boiling point of the least volatile compound in the sample), rapidly vaporized, and pushed out by the carrier gas toward the column. In split injection, some of the carrier gas is bled to waste, such that only a fraction of the sample makes it onto the column.

Columns. GC columns are very long (10–100 m) capillaries with narrow inner diameters (0.1–0.75 mm), spooled up inside an oven with precise temperature control. With the small column diameters, split injections help ensure that columns are not overloaded with sample. The inner wall of capillary columns is coated with a thin layer of stationary phase. Polydimethylsiloxanes with different functional groups are common stationary phases, frequently providing the requisite levels of temperature stability and chemical inertness. Oven temperatures range from 30 °C to 300 °C.

With much higher diffusion rates in the gas phase, optimization of flow rate is more important for minimization of plate height in GC than it is in LC. Temperature programming is used for further optimization. Column temperatures are increased gradually or in steps over the course of a separation.

Detectors. The three most common detector types for GC are thermal conductivity (TCD), flame ionization (FID), and mass spectrometers (MS). The TCD is a universal detector, applicable to all analytes, but has lower sensitivity than other detectors. The FID is a quasi-universal detector that responds to oxidizable carbon, and thus most organic compounds. It is low cost and has moderate sensitivity. Analogous to LC, MS detection offers the highest sensitivity and most information about analyte identity, at a much higher cost. There are also several more specialized detectors that offer improved detection limits for certain classes of compounds, but with a smaller scope of compatible analytes.

Compatible Separations

GC columns are RP or NP with partition or adsorption mechanisms. SEC, IEC, HILIC, HIC, and affinity chromatography are not viable strategies with GC. In general, GC offers better sensitivity, higher resolution, and lower costs than HPLC, but its scope is more limited because of the requirement for volatile and thermostable analytes.

Connections

• Instrument designs for GC are conceptually analogous to those for LC (Ch. 20): mobile phase delivery is at the front end, an injector system puts sample on a column, and a detector is located at the end of the column.
• Temperature programming is the GC equivalent of gradient elution in LC (Ch. 19).
• The high resolution, fast run times,  and versatility possible with modern UPLC instruments (Ch. 20) have generally made these systems the preferred multi-purpose systems, whereas GC is a tool best suited to naturally volatile analytes.

Post-Reading Questions

1. Predict the order of elution for hexane (boiling point 68 °C), octane (bp 125 °C), and 1-butanol (bp 117 °C) on a moderately polar GC column.
2. Which mobile phase—N₂, He, or Ar—will best separate the three compounds in Question 1?
3. Under a certain set of conditions, 1-butanol (boiling point 118 °C) elutes at 10 min and 1-pentanol (boiling point 138 °C) elutes at 19 min. What general temperature program would you use to shorten the separation?
4. Which of the following compounds will produce a signal from an FID: SO₂, CO₂, propane, N₂, acetic acid, benzene?
5. Speculate why SEC, IEC, HILIC, HIC, and affinity chromatography are not viable separation mechanisms in GC.

Topic Learning Objectives

The chapter is a primer for the following learning objectives, which will be covered in lecture and/or with additional assigned reading:

• Articulate the differences between LC and GC columns.
• Explain the importance of temperature in GC separations and use boiling points to predict order of elution of sets of analytes.
• Give examples of GC column stationary phases.
• Match the detector types to the most suitable classes of analytes.
• Distinguish between a destructive and non-destructive detector.
• Suggest an optimum order for using multiple detectors.
• Provide a good rationale for choosing between GC and LC.