Metabolomics relative quantitation with mass spectrometry using chemical derivatization and isotope labeling

O’Maille, Grace; Go, Eden P.; Hoang, Linh; Want, Elizabeth J.; Smith, Colin A.; O’Maille, Paul E.; Nordström, Anders; Morita, Hirotoshi; Qin, Chuan; Uritboonthai, Wilasinee; Apon, Junefredo V.; Moore, Richard D.; Garrett, James; Siuzdak, Gary

doi:10.1155/2008/715905

Cited by 20 publications

(25 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The field of metabolomics provides a challenge to analysis and quantification not seen in proteomics or lipidomics due to the global approach required for complete analysis of the metabolome [95]. The metabolome includes a wide array of small molecules that all contribute to metabolic function.…”

Section: Metabolitesmentioning

confidence: 99%

Relative Quantification of Biomarkers Using Mixed-Isotope Labeling Coupled With Ms

et al. 2012

View full text Add to dashboard Cite

The identification and quantification of important biomarkers is a critical first step in the elucidation of biological systems. Biomarkers take many forms as cellular responses to stimuli and can be manifested during transcription, translation, and/or metabolic processing. Increasingly, researchers have relied upon mixed-isotope labeling (MIL) coupled with MS to perform relative quantification of biomarkers between two or more biological samples. MIL effectively tags biomarkers of interest for ease of identification and quantification within the mass spectrometer by using isotopic labels that introduce a heavy and light form of the tag. In addition to MIL coupled with MS, a number of other approaches have been used to quantify biomarkers including protein gel staining, enzymatic labeling, metabolic labeling, and several label-free approaches that generate quantitative data from the MS signal response. This review focuses on MIL techniques coupled with MS for the quantification of protein and small-molecule biomarkers.

show abstract

Section: Metabolitesmentioning

confidence: 99%

Relative Quantification of Biomarkers Using Mixed-Isotope Labeling Coupled With Ms

et al. 2012

View full text Add to dashboard Cite

show abstract

“…O´Maille et al [39] demonstrated the potential of the stable isotope labeling approach for detecting disease biomarkers in human serum samples by LC-MS. Light and heavy versions of succinic acid ( 13 C 0 and 13 C 4 ) and butanol (d 0 and d 9 ) were utilized for synthesizing derivatization reagents for the relative quantitation of hydroxyl and carboxylic acid-containing metabolites, respectively. Data obtained from patients with sepsis were compared to control patients with systemic inflammatory response syndrome showing three potential sepsis biomarkers.…”

Section: Carboxylic Acid Containing Metabolitesmentioning

confidence: 99%

Isotopic Labeling of Metabolites in Drug Discovery Applications

Iglesias¹,

Sleno²,

Volmer

2012

CDM

View full text Add to dashboard Cite

Understanding the metabolic and pharmacokinetic fate of a drug in humans is a key factor in its development and registration, as well as in the elaboration of new therapeutic agents. To carry out these studies, stable isotope labeling techniques have been effectively used by drug metabolism scientists and toxicologists in order to gain better understanding of the drugs' disposition, bioavailability and toxicity in in vivo studies. Among the different analytical techniques used, mass spectrometry (MS) coupled to separation techniques has become the detection method of choice due to its high sensitivity and selectivity. In vitro quantification of metabolite levels in biofluids by MS is often difficult if a proper internal standard is not available due to the inherent problems associated with the technique (e.g. chromatographic coelutions, ion suppression, low reproducibility etc.). Stable isotope coding approaches alleviate these drawbacks and allow comparative drug metabolomics studies similarly to the differential proteomic techniques developed in the last decade. This review describes a selection of methodological improvements in the use of stable isotopes labeling in combination with MS to detect drug metabolites. In the first part of the paper, the application of labeled compounds to study the absorption, distribution, metabolism, excretion and toxicology of drugs (ADMET) in addition to the elucidation of metabolic pathways is presented. In the second part, recent developments of stable isotope coded tags for the in vitro relative metabolite quantification in biofluids are presented.

show abstract

“…Der Extraktionsüberstand wird anschließend im Vakuum eingedampft und im LC‐Laufmittel rekonstituiert 53. 55–56 Mit dieser Extraktion gefolgt von einer HPLC‐ESI‐MS/MS‐Methode (ESI mit Positivionen‐Detektion; Dauer 60 min) haben Crews et al. mehr als 4000 Signale reproduzierbar in Plasma und CSF detektieren können.…”

Section: Probenvorbereitung Für Fia‐ms/ms Und Hplc‐ms/msunclassified

“…Eine Möglichkeit, um die ESI für Neutralverbindungen zu verbessern, bietet die Derivatisierung mit sauren oder basischen Gruppen. Die Derivatisierung kann auch genutzt werden, um die Ionisierungsfähigkeit von Molekülen zu steigern, die schwach saure oder basische Gruppen tragen 55. 64–67 Um die Ionisierung von schwachen Säuren wie Carbonsäuren (p K S ≈6) zu erleichtern, bietet sich eine Derivatisierung mit einer Aminosulfonsäure (z.…”

Section: Hplc‐ms/ms‐analyse Von Lipiden In Körperflüssigkeitenunclassified

“Targeted Metabolomics” in der Biomarkerforschung

et al. 2010

View full text Add to dashboard Cite

Der Begriff “Metabolomics” bezeichnet ein wissenschaftliches Betätigungsfeld, das im ureigenen Sinn interdisziplinär ist und in dem analytische Chemie, Plattformtechnologie, Massenspektrometrie und NMR‐Spektroskopie sowie Datenanalyse kombiniert zum Einsatz kommen. Angewendet in der Biomarkerforschung schließt das Gebiet die Pathobiochemie, Systembiologie, Medizin und molekulare Diagnostik mit ein, ebenso wie Bioinformatik und multivariate Statistik. Nachdem Metabolomics‐Ansätze im Screening angeborener Stoffwechselstörungen bei Neugeborenen mittlerweile fest etabliert sind, weitet sich die Anwendung in der diagnostischen Forschung gegenwärtig auf eine zunehmende Zahl an Erkrankungen aus. Hier werden die wichtigsten technischen Voraussetzungen sowie neuere Entwicklungen auf den Gebieten Metabolomics und Datenanalyse herausgestellt. Das Hauptaugenmerk liegt auf der Biomarker‐Identifizierung und ‐Qualifizierung sowie auf “Targeted Metabolomics” mithilfe von Hochdurchsatz‐Massenspektrometrie.

show abstract

Metabolomics relative quantitation with mass spectrometry using chemical derivatization and isotope labeling

Cited by 20 publications

References 23 publications

Relative Quantification of Biomarkers Using Mixed-Isotope Labeling Coupled With Ms

Relative Quantification of Biomarkers Using Mixed-Isotope Labeling Coupled With Ms

Isotopic Labeling of Metabolites in Drug Discovery Applications

“Targeted Metabolomics” in der Biomarkerforschung

Contact Info

Product

Resources

About