Derivatization Techniques in Mass Spectrometry: Unlocking the Low-Abundance Metabolome

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Metabolomic Profiling Technology".

Deadline for manuscript submissions: 20 November 2026 | Viewed by 358

Special Issue Editors


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Guest Editor
School of Biomedical Engineering and Health, Wuhan Textile University, Wuhan 430200, China
Interests: separation and analysis technologies; novel mass spectrometry-based metabolomics analysis methods; sub-metabolome database construction; chromatography-mass spectrometry analysis; metabolomics

E-Mail Website
Guest Editor
School of Biomedical Engineering and Health, Wuhan Textile University, Wuhan 430200, China
Interests: separation and analysis technologies; novel mass spectrometry-based metabolomics analysis methods; sub-metabolome database construction; chromatography–mass spectrometry analysis; metabolomics

Special Issue Information

Dear Colleagues,

The comprehensive characterization of the metabolome remains a significant challenge, particularly for low-abundance metabolites that often possess critical biological functions but suffer from poor ionization efficiency or low concentrations in complex matrices. This Special Issue, titled "Derivatization Techniques in Mass Spectrometry: Unlocking the Low-Abundance Metabolome," aims to highlight recent advancements in chemical derivatization and probe-based strategies designed to overcome these analytical barriers.

We invite researchers to submit original articles, reviews, and method developments focusing on novel tagging reagents, isotope-coded probes, and affinity enrichment strategies that enhance detection sensitivity, selectivity, and structural elucidation in mass spectrometry. Topics of interest include, but are not limited to, the following:

  • Design and synthesis of new MS probes for specific functional groups (e.g., amines, carboxyls, carbonyls).
  • Strategies to improve ionization efficiency and chromatographic behavior.
  • Applications of derivatization in targeted and untargeted metabolomics for biomarker discovery.
  • Integration of chemical labeling with advanced MS platforms.
  • Quantitative metabolomics using stable isotope-labeled probes.

By showcasing cutting-edge methodologies and their applications in biology, medicine, and environmental science, this issue seeks to provide a comprehensive overview of how derivatization techniques are reshaping our ability to explore the "dark matter" of the metabolome.

Prof. Dr. Yuqi Feng
Prof. Dr. Quanfei Zhu
Guest Editors

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Keywords

  • chemical derivatization
  • mass spectrometry probes
  • low-abundance metabolites

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Published Papers (1 paper)

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Research

14 pages, 3480 KB  
Article
Iodoacetamine-Alkyne Derivatization-Based Liquid Chromatography–Mass Spectrometry Method for Quantification of Thiol Metabolites in Serum Samples of Hepatocellular Carcinoma Patients
by Chun Mei, Xin-Ze Wu, Hua-Ming Xiao, Azamat Temerdashev, Na An, Quan-Fei Zhu and Yu-Qi Feng
Metabolites 2026, 16(5), 345; https://doi.org/10.3390/metabo16050345 - 20 May 2026
Viewed by 155
Abstract
Background/Objectives: The dysregulation of thiol metabolites is strongly linked to hepatocellular carcinoma (HCC) pathogenesis. However, quantifying these highly polar and oxidation-prone thiols in clinical serum samples via conventional liquid chromatography–mass spectrometry (LC-MS) remains challenging due to their poor sensitivity and reproducibility. Methods [...] Read more.
Background/Objectives: The dysregulation of thiol metabolites is strongly linked to hepatocellular carcinoma (HCC) pathogenesis. However, quantifying these highly polar and oxidation-prone thiols in clinical serum samples via conventional liquid chromatography–mass spectrometry (LC-MS) remains challenging due to their poor sensitivity and reproducibility. Methods: We developed a sensitive and robust iodoacetamine-alkyne (IAM) derivatization–based LC-MS method for quantification of seven trans-sulfuration pathway thiols in human serum. Results: IAM derivatization markedly improved the method’s specificity due to enhanced chromatographic retention and diagnostic MS/MS fragments containing both the alkyne tag and analyte backbone. Sensitivity increased 33-to-160-fold versus underivatized analytes, with limits of detection of 0.02–0.1 nM. All analytes exhibited good linearity, acceptable precision with intra-day and inter-day relative standard deviations in the range of 1.2–13.8%, and high recovery from 88.6% to 102.9%. Conclusions: From the thiol quantification in human serum from 40 HCC patients and 40 healthy controls, it was found that levels of cysteine, homocysteine, glutathione, and cysteinylglycine were significantly lower in HCC patients (p < 0.05). A two-variable logistic regression model using cysteine and cysteinylglycine achieved 90.0% specificity and 80.0% sensitivity for robust HCC discrimination between HCC patients and healthy controls to some extent, with an area under the receiver operating characteristic curve of 0.88 (95% confidence interval: 0.792–0.968). Full article
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