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Mass Spectrometry in High-Throughput Clinical Biomarker Assays: Multiple Reaction Monitoring

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Chemical Diagnostics

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 336))

Abstract

Clinical biomarker discovery, verification, and validation are facilitated by the latest technological advances in mass spectrometry. It is now possible to analyze simultaneously group of tens or hundreds of biomarkers in a blood sample using multiple reaction monitoring (MRM), a tandem mass spectrometric method. However, these newly-developed methods face new challenges, including standardization, calibration, and the determination of analytical and biological variation. Here we illustrate the background, pre-analytical sample preparation, and biomarker assay development using an MRM-mass spectrometric method. In addition, special attention is given to future standardization methods to enable widespread use of the technology.

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Abbreviations

APO4:

Apolipoprotein A4

AUC:

Area under the curve

CE:

Collision energy

CID:

Collision-induced dissociation

CV:

Coefficient of variation

CVD:

Cardiovascular disease

DDA:

Data-dependent acquisition

EDRN:

Early Detection Research Network

EDTA:

Ethylenediamine tetraacetic acid

ESI:

Electrospray ionization

HUPO:

Human Proteome Organization

iMALDI:

Immuno-matrix-assisted laser-desorption/ionization

iTRAQ™:

Isobaric tag for relative and absolute quantitation

LC:

Liquid chromatography

LOD:

Limit of detection

LOQ:

Limit of quantitation

MALDI:

Matrix-assisted laser-desorption/ionization

MMP8:

Matrix metalloproteinase-8

MRM:

Multiple reaction monitoring

MS/MS:

Tandem mass spectrometry

PSA:

Prostate specific antigen

Q1 (Q2, Q3):

Quadrupole 1 (quadrupole 2, quadrupole 3)

QUAD:

The Quantitative Assay Database

ROC:

Receiver operator curve (or receiver operator characteristic)

SIS peptides:

Stable-isotope-labeled internal standard peptides

SISCAPA:

Stable isotope standards and capture by anti-peptide antibodies

SRM:

Selected reaction monitoring

UHPLC:

Ultrahigh-performance liquid chromatography

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Authors and Affiliations

  1. University of Victoria – Genome BC Proteomics Centre, University of Victoria, #3101-4464 Markham Street, Vancouver Island Technology Park, Victoria, BC, V8Z 7X8, Canada

    Carol E. Parker, Dominik Domanski, Andrew J. Percy, Andrew G. Chambers, Alexander G. Camenzind, Derek S. Smith & Christoph H. Borchers

  2. Department of Biochemistry and Microbiology, University of Victoria, Petch Building, Room 207, 3800 Finnerty Rd., Victoria, BC, V8P 5C2, Canada

    Christoph H. Borchers

Authors
  1. Carol E. Parker
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  2. Dominik Domanski
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  7. Christoph H. Borchers
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Correspondence to Christoph H. Borchers .

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Editors and Affiliations

  1. Dept. of Chemical Pathology and Lab. of Genetics of Disease Suscept., The Chinese University of Hong Kong, Hong Kong, People's Republic of China

    Nelson L.S. Tang

  2. Department of Paediatrics and Proteomics Laboratory, The Chinese University of Hong Kong, Hong Kong, People's Republic of China

    Terence Poon

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© 2012 Springer-Verlag Berlin Heidelberg

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Parker, C.E. et al. (2012). Mass Spectrometry in High-Throughput Clinical Biomarker Assays: Multiple Reaction Monitoring. In: L.S. Tang, N., Poon, T. (eds) Chemical Diagnostics. Topics in Current Chemistry, vol 336. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2012_353

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