Applications for Clinical Diagnostics
More and more fast, accurate methods using MS will be introduced for diagnosis and also for prognosis. This will make the healthcare industry flourish in the near future.
Mass spectrometry (MS) is a tool with great specificity and sensitivity. With the use of chromatography as a sample introduction system to MS, it gets much better separation and isolation capability. The gas chromatography (GC) with MS or liquid chromatography (LC) with MS have been successfully employed as the best analytical tools in many different fields including clinical diagnostics.
The MS can be also connected to inductively coupled plasma (ICP) atomic emission spectroscopy (ICP-AES) for diagnosis of elements in clinical samples. The ICP with MS (ICP-MS) gives a very high sensitivity and specificity for the analysis of toxic and other essential elements in clinical samples. MS is a technique that measures ions in the gaseous state. Samples are introduced into an ion source, ionized, and then separated in a mass analyzer according to their mass-to-charge ratio (m/z). In terms of chromatography and MS, initially GC-MS was used for biological analysis but the GC needs a volatile analyte implying that extraction and derivatization protocols were needed for analysis of the polar, thermally labile, and nonvolatile biomolecules found in clinical samples. LC is a much more appropriate separation technique for these polar, thermally labile molecules found in biological samples. It also reduces the need for derivatization to volatile molecules. It is the coupling of LC and MS that led to the adoption of clinical MS. The GC-MS is being used for some specific applications, even if derivatization is required. The tandem mass spectrometry (MS/MS) can provide the speed in addition to increase in specificity and sensitivity. Triple quadrupole (TQ) MS with GC and LC has great advantage over the single quad (SQ) MS system.
With unique ultra-fast MS, which provides ultra-fast scanning and ultra-fast switching capability, Shimadzu has immerged as one of the leading players in clinical diagnostics with several installations in different clinical labs.
With a huge data base available for metabolites, the time for developing the method/s is saved. The following methods have been developed: new born screening (NBS) by tandem LCMS; inborn errors of metabolic (IEM) disorders by GC-MS; vitamins D2/D3 by LC-MS; therapeutic drug monitoring (TDM) by LC-MS/MS; applications in the field of forensic toxicology by LC-MS/MS; analysis of steroids by LC-MS/MS; analysis of catecholamines in blood plasma by LC-MS/MS; and analysis of toxic elements such as As, Pb, Hg, Cd, etc. in clinical samples by using ICP-MS.
All above applications are very critical in diagnosis. However, IEM/NBS are more important in the present context. IEM are disorders caused by gene defect, which might be visible after the birth or within a few days or weeks after the birth. Most IEM are due to defects in any of the key enzymes of various metabolic pathways leading to accumulation of compounds, which follow an alternative pathway of metabolism. This results in the production of toxic metabolites and/or deficiency of biologically important compounds. The individual metabolic disorder may be rare but collectively it is present in one out of 500 newborns. This is the reason why NBS is necessary. There are about 20 primary and 22 secondary metabolites. The careful analysis and early detection can prevent the disease by giving proper treatment. Tandem LCMS is used for NBS and GC-MS is used for confirmation of some of the disorders. In the US of America, Europe, and in the developed countries, NBS is mandatory. In India it is not. The cost of test, expertise, and the facilities are not yet adequately available for the large population in India to be tested and diagnosed. However, for creating a strong India, it is essential to have NBS mandatory. The Government of India is budgeting a good amount of funding for child health and welfare. With the growth of the middle class population in India, the awareness will increase and with proper promotion, it is going to be a part of tests to be carried out for newborns.
We are sure that more and more fast, accurate methods using MS will be introduced for diagnosis and also for prognosis. This will make the healthcare industry flourish in the near future.
