4.6 Article

Isotope labelled in suit derivatization-extraction integrated system for amine/phenol submetabolome analysis based on nanoconfinement effect: Application to lung cancer

期刊

JOURNAL OF CHROMATOGRAPHY A
卷 1670, 期 -, 页码 -

出版社

ELSEVIER
DOI: 10.1016/j.chroma.2022.462954

关键词

In suit derivatization; Integrated system; Nanoconfinement effect; Sample preparation; Isotope labelling derivatization

资金

  1. National Natural Science Funds of China [81973464/H3203, 21775134, 82104126/H3410]
  2. Liaoning Distinguished Professor Project (2017)
  3. Shenyang Science and Technology Innovation Project for Young, Middle-aged Talents [RC190505]
  4. Liaoning BaiQianWan Talents Program in 2019 [A-37]
  5. Liaoning Provincial Doctoral Research Start-up Fund Project (2020)

向作者/读者索取更多资源

In this study, an isotope labelled in suit derivatization-extraction integrated system was proposed for targeted analysis of all the metabolites in the amine/phenol submetabolome using LC-MS. The system demonstrated high efficiency, good repeatability, simple pretreatment steps, and high detection sensitivity and accuracy. It has the potential to be a useful tool for clinical biomarker discovery in disease.
Amine/phenol submetabolome has shown critical role in clinical cancer screening and therapy. In suit derivatization has widely applied in the analysis of amine/phenol submetabolome by LC/MS for simpli-fying the pretreatment procedures, improving the separation and sensitivity. However, the complexity of biological matrix and trace amount of metabolites in plasma that lead to the limited detection cov-erage, poor repeatability and low extraction efficiency are still issues for in suit derivatization. Herein, we proposed an isotope labelled in suit derivatization-extraction integrated system for targeted analysis of all the metabolites in amine/phenol submetabolome with high efficiency and repeatability by LC-MS. The processes of in suit derivatization, alkalization and extraction were performed simultaneously in the nanopores highly dispersed between the carbon nanofibers based on the nanoconfinement effect. Isotope labelling derivatization (ILD) reagents benzoyl chloride (BzCl) and BzCl-d(5) were used to enhance the ac-curacy of identification and relative quantification. The detection sensitivity was increased up to 5.91-fold and detection coverage was enhanced more than 25% compared with conventional derivatization method. After systematical validation, the established methodology was applied to profile the amine/phenol sub-metabolome of human plasma and 1498 metabolites were screened out, among which, 1004 (67.02%) were positively or putatively identified. Furthermore, 106 amine/phenol metabolites exhibited significant difference between lung cancer patients and healthy controls by using multiple data processing meth-ods. Taken together, the isotope labelled in suit derivatization-extraction integrated system was a useful approach for the analysis of amine/phenol submetabolome in plasma with broad metabolome coverage, simple pretreatment steps, high detection sensitivity and accuracy, and could be a potential tool for clin-ical biomarker discovery of disease. (c) 2022 Elsevier B.V. All rights reserved.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据