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Clinical Applications of Mass Spectrometry: Current Applications and Trends for the Future

presented by

Robert Fitzgerald
Professor of Pathology
UCSD

January 16, 2014

TSRI Auditorium


Background:

Dr. Fitzgerald's research interests focus on the use of mass spectrometry in clinical diagnostics. He has been active in developing MS based methods for analysis of testosterone and other biologically important compounds. A second major research area focuses on optimizing how cardiac biomarkers are used clinically, especially in terms of disease diagnosis and monitoring therapeutic interventions.

Abstract:

By providing unequivocal identification and quantification of specific compounds, mass spectrometry (MS) has played a key role in clinical laboratories since the early 1980ís. Advances in instrumentation have solidified this role and allowed for the expansion of mass spectrometry for measuring a wide variety of analytes including: drugs, hormones, vitamins, proteins, and microbes. Key development s that enabled this change were the invention of ionization modes such as electrospray ionization (ESI) and matrix assisted laser desorption ionization (MALDI). New methods of forming gas phase ions have been combined with novel techniques for separating ions such as tandem mass spectrometry (MS/MS) and time of flight (TOF) mass spectrometry. These innovations allow for analysis of large biomolecules which will ensure the expanding role of mass spectrometry in the clinical laboratory.


Isotope dilution quantification is one of the most powerful applications of mass spectrometry in the clinical laboratory. Isotope dilution refers to quantification of a compound of interest relative to an isotopically labeled internal standard. By measuring the peak area of the compound of interest relative to the peak area of a known amount of internal standard accurate and precise quantitative measurements can be obtained. Isotope dilution can be utilized in a variety of ionization and mass separation modes.


ESI combined with liquid chromatography tandem mass spectrometry (LC/MS/MS) often simplifies sample preparation schemes allowing for more efficient use of laboratory staff. Many laboratories have adopted "dilute and shoot" techniques for identifying and quantifying compounds in biological specimens. ESI can also be combined with "intelligent" data acquisition in order to obtain quantitative and qualitative data in a single run. When combined with high resolution accurate mass analysis, ESI provides the ability to obtain scanning data for broad spectrum drug screens. Other applications of ESI include the analysis of steroids in serum specimens. Other applications of ESI include the improved analysis of steroids in serum specimens, testosterone being a clear example.


A relatively new application of MS is in the microbiology laboratory. MALDI/TOF mass spectrometry is being used to directly identify microbes from culture plates decreasing the time required to identify bacterial (and other) infections. In addition to speeding up identifications, MALDI/TOF has increased specificity at reduced costs compared with traditional techniques.


In summary the role of mass spectrometry in the clinical laboratory continues to expand and all clinical chemists should become familiar with the techniques involved.


Learning objectives


After this presentation participants should be able to:


  1. Describe the fundamentals of ion formation and mass to charge analysis.

  2. Describe electron ionization, electrospray ionization, and matrix assisted laser desorption ionization.

  3. Discuss the advantages of isotope dilution mass spectrometry.

  4. Describe how multiple reaction monitoring works with tandem mass spectrometry.

  5. Describe how mass spectrometry is reducing turn-around times in microbiology laboratories.


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