Large-scale targeted metabolomics method for metabolite profiling of human samples

Guodong Cao, Zhengbo Song, Yanjun HONG, Zhiyi Yang, Yuanyuan Song, Zhongjian Chen, Zhaobin Chen, Zongwei CAI*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Targeted metabolomics has significant advantages for quantification but suffers from reduced metabolite coverage. In this study, we developed a large-scale targeted metabolomics method and expanded its applicability to various human samples. This approach initially involved unbiased identification of metabolites in human cells, tissues and body fluids using ultra high-performance liquid chromatography (UHPLC) coupled to high-resolution Orbitrap mass spectrometry (MS). Targeted metabolomics method was established with utility of UHPLC-triple quadrupole MS, which enables targeted profiling of over 400 biologically important metabolites (e.g., amino acids, sugars, nucleotides, dipeptides, coenzymes, and fatty acids), covering 92 metabolic pathways (e.g., Krebs cycle, glycolysis, amino acids metabolism, ammonia recycling, and one-carbon metabolism). The present method displayed better sensitivity, repeatability and linearity than the Orbitrap MS-based untargeted metabolomics approach and demonstrated excellent performance in lung cancer biomarker discovery, in which 107 differential metabolites were able to discriminate between carcinoma and adjacent normal tissues, implicating the Warburg effect, alteration of redox state, and nucleotide metabolism of lung cancer. This new method is flexible and expandable and offers many advantages for metabolomics analysis, such as wide metabolite coverage, good repeatability and linearity and excellent capability in biomarker discovery, making it useful for both basic and clinical metabolic research.

Original languageEnglish
Pages (from-to)144-151
Number of pages8
JournalAnalytica Chimica Acta
Volume1125
DOIs
Publication statusPublished - 15 Aug 2020

Scopus Subject Areas

  • Analytical Chemistry
  • Biochemistry
  • Environmental Chemistry
  • Spectroscopy

User-Defined Keywords

  • Biomarker discovery
  • Human samples
  • Mass spectrometry
  • Targeted metabolomics

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