Quantitative Biological and Clinical Mass Spectrometry: An Introduction
This book is designed to provide information and help to new users of mass spectrometry (MS) working in clinical or biochemical fields who are faced with implementing and designing quantitative mass spectrometric assays for molecules of biological interest. While a working knowledge of basic and physical chemistry and some experience of MS is assumed, there are simple explanations and further sources of information included of the techniques and basic chemistry involved. These will be clearly separately indicated and can be avoided by the majority of the expected readership.
While MS has been used for the quantitative analysis of trace biological molecules since the late 1960s, it has been the rapid development of compact instruments, automation, efficient ionisation methods, modern ion optics, electronics and digital control, and data manipulation methods that has led to a rapid growth of novel applications in the field of clinical and biochemical analysis in recent years. Up until the 1970s MS, developed to assist the oil industry, had principally been used for analysis of small‐molecule gaseous samples. The pharmaceutical industry took up the technique in order to permit the qualitative and quantitative analysis of biologically relevant substances, and in the early 1980s it was the development of methods for handling solutions, liquids and solids and the ability to begin to examine really large molecules and polymers that precipitated the technique into acceptance in a wide variety of fields. In the early 2000s, a couple of reviews1,2 discussed the relevance of MS to clinical practice. The advent of reliable tandem MS (MS/MS) in the 1990s soon made its appearance in clinical analyses on account of the extra dimension of analyte specificity that it provided, but even in 2012 one author still warned that fully automated analysis based on MS/MS combined with liquid chromatography (LC) would take a decade or more to match the current immunoassays in use in hospital laboratories.3
In 2016, an issue of Clinical Chemistry4 was dedicated to current views on the state of use of MS in clinical settings. From an article by Cooks and others on this subject, it is clear to see that much progress has been made in the past decade. The articles in the latter reference cover a number of specific analytical reports, but also include helpful guidelines and indications of future developments. MS is inherently a method for sensitive and specific analysis, but its use in clinical areas has been slow to develop, principally on account of the equally efficient and manipulatively simple immunological‐based assay methods. The latter methods are especially good where automation with very large sample numbers and speed of producing results are involved, and the MS instrument industry is now responding to the competition. A necessary consequence of these developments has been that modern instruments are presented to the operator as a ‘black box’, which makes invisible everything that takes place between the presentation of the sample and the appearance on a computer screen of a result. It can be difficult for an inexperienced operator to recognise that the apparent production of a stream of results may be hiding some serious failure of the basic system. This text is designed to show how the presence of false results can be detected and understood.
MS for use in quantitative biochemistry with smallmolecule drugs, in the pharmaceutical industry, has been the principal driving force for instrumental and method development in recent years. The introduction of biopolymer drugs interacting with the immune system has now propelled the interest in analysis of large biopolymers, and their quantitative analysis is a growing area of research publications.
In the fields of clinical chemistry, as well as in forensic science and sports medicine, a different perspective is found. Two different types of need for a quantitative analysis are present: one is for a precise and validated figure for the concentration in a defined matrix, and the other, while still needing precision, requires a knowledge of whether the concentration exceeds a predetermined permitted or safe level, such as applies in drug misuse or water or food safety considerations. Included in ‘quantitative analysis’ are those experiments designed to discover the absence or presence of a defined analyte. The quantitative aspect lies in knowing the limits of detection that are available in the designed protocol and the confidence in the precise specificity of the assay.
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|May 7, 2018|
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