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Mass Spectrometry-Based Metabolomics for the Clinical Laboratory

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Clinical Metabolomics Applications in Genetic Diseases

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Abstract

In the clinical laboratory, analysis of small molecules using mass spectrometry (MS) primarily encompasses the targeted and quantitative determination of known biomarkers for disease diagnosis and monitoring, general health status evaluation, toxicology, and therapeutic drug monitoring. Although there are exceptions, MS-based assays in the clinical laboratory typically involve the utilization of analyte-specific calibration curves for quantitation, and stable isotope-labeled internal standards to correct for any sample preparation and instrument-related variability. A clinical MS-based assay usually consists of a relatively small panel of biomarkers in a certain diagnostic context that are compatible with the same sample preparation protocol. Alternatively, the term metabolomics generally refers to the comprehensive and systematic large-scale profiling of small molecules within a biological system. Targeted and quantitative MS-based assays containing relatively large panels of small molecules (metabolites) are routinely utilized for newborn screening (NBS), biochemical genetics testing, and toxicology. Broad nontargeted metabolomics investigations have found some utility in the aforementioned testing areas, but are not currently commonplace in the clinical laboratory. This chapter discusses current state-of-the-art MS instrumentation, describes several applications, and provides implementation considerations for MS-based metabolomics in the clinical laboratory.

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Abbreviations

AC:

Alternating current

APCI:

Atmospheric chemical ionization

APPI:

Atmospheric pressure photoionization

CCS:

Collisional cross section

CI:

Chemical ionization

CID:

Collision-induced dissociation

Da:

Dalton

DC:

Direct current

EI:

Electron ionization

ESI:

Electrospray ionization

eV:

Electron volt

FTICR:

Fourier-transform ion cyclotron resonance

FWHM:

Full width at half maximum

GC:

Gas chromatography

HILIC:

Hydrophilic interaction liquid chromatography

HPLC:

High-performance liquid chromatography

HRMS:

High-resolution mass spectrometry

ICP:

Inductively coupled plasma

IEMs:

Inborn errors of metabolism

IMS:

Ion mobility spectrometry

kV:

Kilovolt

LC:

Liquid chromatography

m/z:

Mass-to-charge ratio

MALDI:

Matrix-assisted laser desorption/ionization

MRM:

Multiple-reaction monitoring

MS:

Mass spectrometry

MS/MS:

Tandem mass spectrometry

QTOF:

Quadrupole time-of-flight

RF:

Radiofrequency

TOF:

Time-of-flight

UPLC:

Ultra-high-performance liquid chromatography

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  1. Department of Pathology and Laboratory Medicine, BC Children’s Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada

    Joshua A. Dubland

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Correspondence to Joshua A. Dubland .

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  1. Metabolomics Section, Department of Clinical Genomics, Center for Genome Medicine, King Faisal Specialist Hospital & Research Center (KFSHRC), Riyadh, Saudi Arabia

    Anas M. Abdel Rahman

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Dubland, J.A. (2023). Mass Spectrometry-Based Metabolomics for the Clinical Laboratory. In: Abdel Rahman, A.M. (eds) Clinical Metabolomics Applications in Genetic Diseases. Springer, Singapore. https://doi.org/10.1007/978-981-99-5162-8_2

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