GC-MS is a combination of gas chromatography, a separation technique, and mass spectrometry, which is used to identify analytes. This detection technique has extensive applications in biomedicine, including disease diagnosis, pharmaceutical quality control, and metabolic profiling.
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GC-MS is a technique used for analysis of volatile and semi-volatile compounds. Gas chromatography is a potent separation technique capable of separating compounds in gaseous form. GC can identify substances based on their retention time, but these can be inaccurate and therefore misleading. GC itself is not enough to confidently identify the separated compounds, which is the reason for the use of mass spectrometry.
Mass spectrometry identifies analytes based on their mass, or their m/z (mass to charge ratio). Typically, GC-MS utilizes electron impact and chemical ionization techniques. Overall, GC-MS confers several advantages, such as faster analysis, improved confidence in analyte identification, and better sensitivity for compounds that are otherwise hard to analyze.
GC-MS for disease diagnosis
GC-MS is particularly useful in the diagnosis of disease as it can identify compounds in fluids such as urine and blood. Diseases which might otherwise have been difficult to detect, such as congenital disease, benefit particularly from this as it can be applied to samples of amniotic fluid. In this situation, GC-MS offers a highly accurate diagnosis of conditions that could be very relevant during childbirth or critical postnatal periods.
GC-MS can be used to detect disease states based on abnormal levels of compounds in bodily fluids. For example, deficiencies in cholesterol synthesis can lead to Smith-Lemli-Opitz syndrome (SLO), which can be detected using GC-MS, which shows increased levels of 7-dehydrocholestrol in blood and tissues.
The technique has also been used to identify the biomarkers of pulmonary tuberculosis present in the human breath. This biomarker test was capable of distinguishing between healthy individuals and those with suspected infection, and between infected and noninfected patients.
GC-MS in metabolomics
GC-MS can be used to detect and characterize metabolic imbalances in adults and juveniles. Urine tests performed at birth can inform healthcare personnel of metabolic diseases at an early stage. These include the inborn errors of metabolism (IEM) which affect around 1 in 200 infants.
An IEM is caused by loss or gain of function of one or more mutant proteins, and the GC-MS metabolite analysis can identify a number of the abnormalities resulting from the enzyme dysfunction. GC-MS techniques can be used to detect over 130 different metabolic disorders, such as methylmalonic aciduria, propionic acidemia, and isovaleric aciduria.
GC-MS can also be used to characterize metabolic activity, and shows if an abnormal metabolic profile has been acquired. The metabolic process can be isotopically labeled, typically with 13C, and the ratios of 13C-12C are usually measured with an isotope ratio mass spectrometer. This type of mass spectrometer is used to measure only a number of chosen ions and gives the values in the form of ratios.
The use of GC-MS in the analysis of bodily fluids has certain disadvantages, too. For example, repeatedly injecting bodily fluids into a gas chromatographer can result in an involatile residue, which may decompose during later analysis. Furthermore, GC-MS is ideal for volatile metabolites, but is less ideal for non-volatile metabolites with high molecular mass.
Drug development and production
GC-MS is of great use in drug development, as it forms an important aspect of medicinal chemistry. It can be used to characterize leading candidate compounds which should be further followed up in the process of drug development and the search for active pharmaceutical ingredients (API).
GC-MS can be used to analyze drug behavior during a clinical trial. Pharmacokinetics (the study of how pharmaceuticals move around the body), and pharmacodynamics (the study of how the drug’s effect and how they work) can be studied using GC-MS. For example, GC-MS has been used to determine the pharmacokinetics and pharmacodynamics of capsules of vitamin K in human plasma.
GC-MS has a prominent role in quality control of pharmaceuticals. It can be used to separate components of pharmaceuticals and identify them because of its ability to characterize compounds. Any impurities will therefore be identified and can be removed. As such, GC-MS has a role in the process and method development in pharmaceutical production as well as in testing stability of pharmaceuticals.