Liquid samples are pumped through a metal capillary maintained at 3 to 5 kV and nebulised at the tip of the capillary to form a fine spray of charged droplets. 1 ESI works well with moderately polar molecules and is thus well suited to the analysis of many metabolites, xenobiotics and peptides.

4 The current review focuses on the principles of LC-MS, practical considerations in setting up LC-MS assays and reviews some of the major applications in clinical biochemistry, concentrating on small molecule applications.ДЇenn developed ESI into a robust ion source capable of interfacing to LC and demonstrated its application to a number of important classes of biological molecules. Applications of electrospray MS were reviewed in The Clinical Biochemist Reviews in 2003. The reasons for choosing LC-MS over LC with conventional detectors are essentially the same as with GC-MS, namely high specificity and the ability to handle complex mixtures. 3 There are a number of other clinical applications of LC-MS, and the technique is more generally applicable than GC-MS owing to the broader range of biological molecules that can be analysed and the greater use of LC separations in clinical laboratories. Biochemical genetics was one of the first areas to do so, and the analysis of neonatal dried blood spot samples for a range of inborn errors of metabolism was a major early application. 2Д«y the mid 1990s, the price and performance of LC-MS instruments had improved to the extent that clinical biochemistry laboratories were able to take advantage of the new technology. Fenn was awarded the Nobel Prize in 2002 with Koichi Tanaka who developed matrix assisted laser desorption ionisation, another extremely useful MS ionisation technique for the analysis of biological molecules. 1 Manufacturers rapidly developed instruments equipped with electrospray sources, which had a great impact on protein and peptide biochemistry. This situation changed with the development of the electrospray ion source by Fenn in the 1980s. Several interfaces were developed but they were cumbersome to use and unreliable, so uptake by clinical laboratories was very limited. The coupling of MS with LC (LC-MS) was an obvious extension but progress in this area was limited for many years due to the relative incompatibility of existing MS ion sources with a continuous liquid stream. screening urine samples for inborn errors of metabolism or drugs. Relatively cheap and reliable GC-MS systems are now a feature of many clinical biochemistry laboratories and are indispensable in several areas where the analysis of complex mixtures and unambiguous identification is required e.g. The coupling of gas chromatography to MS (GC-MS) was achieved in the 1950s with commercial instruments available from the 1970s. Coupling of MS to chromatographic techniques has always been desirable due to the sensitive and highly specific nature of MS compared to other chromatographic detectors.

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