Gas chromatography–mass spectrometry (GC–MS) techniques are a fundamental part of the analytical armory in many laboratories
and can provide both qualitative and quantitative information on gas-phase analytes across all industrial applications. First
introduced in the 1950s, these instruments typically use electron ionization (EI) or chemical ionization (CI) techniques to
produce charged gas-phase species that are subsequently analyzed according to their mass-to-charge ratio (m/z) by a host of analyzer types, including quadrupole, ion-trap, time-of-flight (TOF), magnetic sector, and Fourier transform
MS instruments, depending on the resolution and mass accuracy required by the application. Electron ionization is the most
popular technique and is a higher energy technique capable of producing fragmentation of the analyte species to aid with structural
elucidation or provide confirmatory ions for quantitative analysis. Chemical ionization is a much softer ionization technique
and is typically used to improve the yield of the pseudomolecular ion or increase sensitivity, especially with halogenated
For many years, MS-MS or MSn spectral experiments have been possible with GC applications, via ion-trap (so-called tandem in time) instruments. These instruments can yield very highly selective data for structural elucidation; however, they provide low
mass accuracy and low resolution, and the instrumentation often suffers from issues with linearity of response. Modern tandem
mass spectrometry applications demand high sensitivity, high mass accuracy, and high resolution, and as such, most modern
GC–MS-MS applications typically use "tandem in space" methods using analyzer combinations shown in Table I and have only relatively
recently realized widespread commercial availability. The most commercially popular instruments are the triple-quadrupole
(QqQ) and quadrupole–time-of-flight (QTOF) combinations, both of which use a multipole collision cell between each analyzer
that fragments the ions from the first mass analyzing device before further mass analysis in the second. One notable exception
is the orbitral trap Fourier transform mass analyzer, which is a new generation, orbital ion trap system that can achieve
very high resolution.
Table I: Performance figures of various GC–MS-MS systems
Tandem GC–MS has its own challenges, not least of which is the very highly efficient nature of the technique that gives rise
to peaks which elute in a relatively short time frame. High MS scan rates are required to derive enough measurements within
the elution time of each analyte to render the data meaningful, and this is a primary consideration when choosing the analyzer
combination and setting experimental parameters.
Quantitatively, tandem mass spectrometry is typically used to achieve deconvolution of highly complex samples in analyses
in which one needs to determine analyte concentration at trace levels, which is achieved through the specificity derived by
tuning the various mass analyzing devices to specific precursor and product ions in each of the analyzing devices. Figure
1 gives a schematic overview of the various experiment types that are possible in GC–MS-MS.
Figure 1: Various MS-MS modes possible with GC–MS-MS.
The inclusion of a high mass accuracy device within the analyzer combination gives the advantage that empirical formulas can
be postulated from the measured mass. The more accurate the device, the fewer empirical formulae that could give rise to the
measured mass, which is a significant advantage in structural elucidation. The high mass accuracy of QTOF and orbitral trap
instruments make them popular choices for structural elucidation work.