Gas chromatography–mass spectrometry
Gas chromatography–mass spectrometry is an analytical method that combines the features of gas-chromatography and mass spectrometry to identify different substances within a test sample. Applications of GC–MS include drug detection, fire investigation, environmental analysis, explosives investigation, food and flavor analysis, and identification of unknown samples, including that of material samples obtained from planet Mars during probe missions as early as the 1970s. GC–MS can also be used in airport security to detect substances in luggage or on human beings. Additionally, it can identify trace elements in materials that were previously thought to have disintegrated beyond identification. Like liquid chromatography–mass spectrometry, it allows analysis and detection even of tiny amounts of a substance.
GC–MS has been regarded as a "gold standard" for forensic substance identification because it is used to perform a 100% specific test, which positively identifies the presence of a particular substance. A nonspecific test merely indicates that any of several in a category of substances is present. Although a nonspecific test could statistically suggest the identity of the substance, this could lead to false positive identification. However, the high temperatures used in the GC–MS injection port can result in thermal degradation of injected molecules, thus resulting in the measurement of degradation products instead of the actual molecule of interest.
History
The first on-line coupling of gas chromatography to a mass spectrometer was reported in the late 1950s. An interest in coupling the methods had been suggested as early as December 1954, but conventional recording techniques had too poor temporal resolution. Fortunately, time-of-flight mass spectrometry developed around the same time allowed to measure spectra thousands times a second.The development of affordable and miniaturized computers has helped in the simplification of the use of this instrument, as well as allowed great improvements in the amount of time it takes to analyze a sample. In 1964, Electronic Associates, Inc., a leading U.S. supplier of analog computers, began development of a computer controlled quadrupole mass spectrometer under the direction of Robert E. Finnigan. By 1966 Finnigan and collaborator Mike Uthe's EAI division had sold over 500 quadrupole residual gas-analyzer instruments. In 1967, Finnigan left EAI to form the Finnigan Instrument Corporation along with Roger Sant, T. Z. Chou, Michael Story, Lloyd Friedman, and William Fies. In early 1968, they delivered the first prototype quadrupole GC/MS instruments to Stanford and Purdue University. When Finnigan Instrument Corporation was acquired by Thermo Instrument Systems in 1990, it was considered "the world's leading manufacturer of mass spectrometers".
Instrumentation
The GC–MS is composed of two major building blocks: the gas chromatograph and the mass spectrometer. The gas chromatograph utilizes a capillary column whose properties regarding molecule separation depend on the column's dimensions as well as the phase properties. The difference in the chemical properties between different molecules in a mixture and their relative affinity for the stationary phase of the column will promote separation of the molecules as the sample travels the length of the column. The molecules are retained by the column and then elute from the column at different times, and this allows the mass spectrometer downstream to capture, ionize, accelerate, deflect, and detect the ionized molecules separately. The mass spectrometer does this by breaking each molecule into ionized fragments and detecting these fragments using their mass-to-charge ratio.These two components, used together, allow a much finer degree of substance identification than either unit used separately. It is not possible to make an accurate identification of a particular molecule by gas chromatography or mass spectrometry alone. The mass spectrometry process normally requires a very pure sample while gas chromatography using a traditional detector cannot differentiate between multiple molecules that happen to take the same amount of time to travel through the column, which results in two or more molecules that co-elute. Sometimes two different molecules can also have a similar pattern of ionized fragments in a mass spectrometer. Combining the two processes reduces the possibility of error, as it is extremely unlikely that two different molecules will behave in the same way in both a gas chromatograph and a mass spectrometer. Therefore, when an identifying mass spectrum appears at a characteristic retention time in a GC–MS analysis, it typically increases certainty that the analyte of interest is in the sample.
Purge and trap GC–MS
For the analysis of volatile compounds, a purge and trap concentrator system may be used to introduce samples. The target analytes are extracted by mixing the sample with water and purge with inert gas into an airtight chamber, this is known as purging or sparging. The volatile compounds move into the headspace above the water and are drawn along a pressure gradient out of the chamber. The volatile compounds are drawn along a heated line onto a 'trap'. The trap is a column of adsorbent material at ambient temperature that holds the compounds by returning them to the liquid phase. The trap is then heated and the sample compounds are introduced to the GC–MS column via a volatiles interface, which is a split inlet system. P&T GC–MS is particularly suited to volatile organic compounds and BTEX compounds.A faster alternative is the "purge-closed loop" system. In this system the inert gas is bubbled through the water until the concentrations of organic compounds in the vapor phase are at equilibrium with concentrations in the aqueous phase. The gas phase is then analysed directly.
Types of mass spectrometer detectors
The most common type of mass spectrometer associated with a gas chromatograph is the quadrupole mass spectrometer, sometimes referred to by the Hewlett-Packard trade name "Mass Selective Detector". Another relatively common detector is the ion trap mass spectrometer. Additionally one may find a magnetic sector mass spectrometer, however these particular instruments are expensive and bulky and not typically found in high-throughput service laboratories. Other detectors may be encountered such as time of flight, tandem quadrupoles , or in the case of an ion trap MSn where n indicates the number mass spectrometry stages.GC–tandem MS
When a second phase of mass fragmentation is added, for example using a second quadrupole in a quadrupole instrument, it is called tandem MS. MS/MS can sometimes be used to quantitate low levels of target compounds in the presence of a high sample matrix background.The first quadrupole is connected with a collision cell and another quadrupole. Both quadrupoles can be used in scanning or static mode, depending on the type of MS/MS analysis being performed. Types of analysis include product ion scan, precursor ion scan, selected reaction monitoring and neutral loss scan. For example: When Q1 is in static mode, and Q3 is in scanning mode, one obtains a so-called product ion spectrum. From this spectrum, one can select a prominent product ion which can be the product ion for the chosen precursor ion. The pair is called a "transition" and forms the basis for SRM. SRM is highly specific and virtually eliminates matrix background.
Ionization
After the molecules travel the length of the column, pass through the transfer line and enter into the mass spectrometer they are ionized by various methods with typically only one method being used at any given time. Once the sample is fragmented it will then be detected, usually by an electron multiplier, which essentially turns the ionized mass fragment into an electrical signal that is then detected.The ionization technique chosen is independent of using full scan or SIM.