Analytical and Bioanalytical Chemistry

, Volume 411, Issue 5, pp 1041–1052 | Cite as

An auxiliary matrix for routine analysis of small molecules and biological macromolecules using matrix-assisted laser desorption ionization mass spectrometry

  • Zhangpei Zhu
  • Jiajia Shen
  • Dawei Wang
  • Chong Chen
  • Yangfan Xu
  • Huimin Guo
  • Dian Kang
  • Naoki Hamada
  • Jing Dong
  • Guangji WangEmail author
  • Yan LiangEmail author
Research Paper


The great hurdles related with matrix-assisted laser desorption/ionization (MALDI) analysis are inhomogeneous crystallization, poor reproducibility, and low sensitivity. To effectively improve the performance of MALDI mass spectrometry (MS), graphene oxide (GO) was first utilized as an auxiliary matrix of the conventional matrices, including 2,5-dihydroxybenzoic acid (DHB), α-cyano-4-hydoxycyanocinnamic acid (CHCA), 2,4,6-trihydroxyacetophenone (THAP), and 3,5-dimethoxy-4-hydroxycinnamic acid (SA), for the analysis of small molecules and biological macromolecules on different MALDI MS systems. The results revealed that the DHB-GO composite matrix could provide much superior crystal homogenization, better reproducibility, higher sensitivity, and more excellent linearity for the statins’ tissue imaging on iMScope than the single-use DHB matrix. Moreover, the DHB-GO dramatically improved the spot-to-spot and shot-to-shot reproducibility, crystal homogenization, sensitivity, and linearity of MALDI-TOF MS for statins’ analysis in dried droplet. The capability of THAP on the analysis of lipids, similarly, could be greatly enhanced by the combined use of GO. THAP-GO composite matrix was expected to be widely used in the MALDI MS-based liposome studies. It was also found that CHCA-GO could provide superior analytical performance for peptides. The sensitivity and reproducibility of intact proteins could be greatly improved by SA-GO composite matrix. More importantly, the better reproducibility produced by the composite matrices sufficiently indicated that low concentration (0.1 mg mL−1) of GO almost did not cause contamination to MALDI MS system. Thus, GO was proved to be a versatile auxiliary matrix for the MALDI MS-based routine analysis of small molecules and biological macromolecules.

Graphical abstract


Graphene oxide Composite matrix Matrix-assisted laser desorption/ionization mass spectrometry Crystal homogenization iMScope 


Author contributions

All authors have given approval to the final version of the manuscript.

Funding information

This study was supported by the National Nature Science Foundation (81573559, 81530098), the Nature Science Foundation of Jiangsu Province (BK20171395), and the National Key Special Project of Science and Technology for Innovation Drugs of China (2017ZX09301013).

Compliance with ethical standards

All the animal experiments in the present study were approved by the Ethical Committee of Animal Experiments of China Pharmaceutical University.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2018_1532_MOESM1_ESM.pdf (167 kb)
ESM 1 (PDF 166 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Zhangpei Zhu
    • 1
  • Jiajia Shen
    • 1
  • Dawei Wang
    • 2
  • Chong Chen
    • 1
  • Yangfan Xu
    • 1
  • Huimin Guo
    • 1
  • Dian Kang
    • 1
  • Naoki Hamada
    • 3
  • Jing Dong
    • 3
  • Guangji Wang
    • 1
    Email author
  • Yan Liang
    • 1
    Email author
  1. 1.Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjingChina
  2. 2.Affiliated Hospital of Integrated Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjingChina
  3. 3.Shimadzu China Mass Spectrometry CenterBeijingChina

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