Volume 13 Issue 11
Nov.  2023
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Jie Han, Shilin Gong, Xiqing Bian, Yun Qian, Guilan Wang, Na Li, Jian-Lin Wu. Polarity-regulated derivatization-assisted LC-MS method for amino-containing metabolites profiling in gastric cancer[J]. Journal of Pharmaceutical Analysis, 2023, 13(11): 1353-1364. doi: 10.1016/j.jpha.2023.06.009
Citation: Jie Han, Shilin Gong, Xiqing Bian, Yun Qian, Guilan Wang, Na Li, Jian-Lin Wu. Polarity-regulated derivatization-assisted LC-MS method for amino-containing metabolites profiling in gastric cancer[J]. Journal of Pharmaceutical Analysis, 2023, 13(11): 1353-1364. doi: 10.1016/j.jpha.2023.06.009

Polarity-regulated derivatization-assisted LC-MS method for amino-containing metabolites profiling in gastric cancer

doi: 10.1016/j.jpha.2023.06.009
Funds:

This work was supported by the Science and Technology Development Fund, Macau SAR (Grant No.: 0025/2021/A1), and funded by Natural Science Foundation of Shenzhen (Grant No.: JCYJ20190808115003699), and Major Medical Projects in Zhongshan (Grant No.: 2017B1003).

  • Received Date: Mar. 16, 2023
  • Accepted Date: Jun. 20, 2023
  • Rev Recd Date: Jun. 01, 2023
  • Publish Date: Jun. 26, 2023
  • Amino-containing compounds, including amino acids, aliphatic amines, aromatic amines, small peptides and catecholamines, are involved in various biological processes and play vital roles in multiple metabolic pathways. Previous studies indicated that some amino-containing metabolites are significant diagnostic and prognostic biomarkers of gastric cancer. However, the discovery of precise biomarkers for the preoperative diagnosis of gastric cancer is still in an urgent need. Herein, we established a polarity-regulated derivatization method coupled with liquid chromatography-mass spectrometry (LC-MS) for amino-containing metabolites profiling in the serum samples of patients with gastric cancer and healthy controls, based on our newly designed and synthesized derivatization reagent (S)-3-(1-(diisopropoxyphosphoryl) pyrrolidine-2-carboxamido)-N-hydroxysuccinimidyl ester (3-DP-NHS). Enhanced separation efficiency and detection sensitivity for amino-containing metabolites were achieved after derivatization. This method exhibited good linearity, recovery, intra- and inter-day precision and accuracy. Only 5 μL serum is needed for untargeted analysis, enabling 202 amino-containing metabolites to be detected. Statistical analysis revealed altered amino acid metabolisms in patients with gastric cancer. Furthermore, ultra high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS/MS) analysis quantification revealed increased serum levels of tryptamine and decreased concentrations of arginine and tryptophan in patients with gastric cancer. Receiver operating characteristic (ROC) curves indicated that an increased tryptamine/tryptophan ratio could serve as a potential biomarker for gastric cancer diagnosis. This study demostrated the possibility of using serum amino acid biomarkers for gastric cancer diagnosis, providing new avenues for the treatment of gastric cancer.
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