Integrated LC-MS metabolomics with dual derivatization for quantification of FFAs in fecal samples of hepatocellular carcinoma patients

FFAs display pleiotropic functions in human diseases. Short-chain FAs (SCFAs), medium-chain FAs, and long-chain FAs are derived from different origins, and precise quantification of these FFAs is critical for revealing their roles in biological processes. However, accessing stable isotope-labeled in...

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Autores principales:	Jiangang Zhang, Shuai Yang, Jingchun Wang, Yanquan Xu, Huakan Zhao, Juan Lei, Yu Zhou, Yu Chen, Lei Wu, Mingyue Zhou, Yan Li, Yongsheng Li
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	FFAs short-chain FAs LC-MS isotope-free derivatization 2-dimethylaminoethylamine Biochemistry QD415-436
Acceso en línea:	https://doaj.org/article/fa1702e85bf54cc18f43a00139967ce1
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spelling	oai:doaj.org-article:fa1702e85bf54cc18f43a00139967ce12021-11-14T04:27:39ZIntegrated LC-MS metabolomics with dual derivatization for quantification of FFAs in fecal samples of hepatocellular carcinoma patients0022-227510.1016/j.jlr.2021.100143https://doaj.org/article/fa1702e85bf54cc18f43a00139967ce12021-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0022227521001255https://doaj.org/toc/0022-2275FFAs display pleiotropic functions in human diseases. Short-chain FAs (SCFAs), medium-chain FAs, and long-chain FAs are derived from different origins, and precise quantification of these FFAs is critical for revealing their roles in biological processes. However, accessing stable isotope-labeled internal standards is difficult, and different chain lengths of FFAs challenge the chromatographic coverage. Here, we developed a metabolomics strategy to analyze FFAs based on isotope-free LC-MS-multiple reaction monitoring integrated with dual derivatization. Samples and dual derivatization internal standards were synthesized using 2-dimethylaminoethylamine or dansyl hydrazine as a “light” label and N,N-diethyl ethylene diamine or N,N-diethyldansulfonyl hydrazide as a “heavy” label under mild and efficient reaction conditions. General multiple reaction monitoring parameters were designed to analyze these FFAs. The limit of detection of SCFAs varied from 0.5 to 3 nM. Furthermore, we show that this approach exhibits good linearity (R2 = 0.99374–0.99929), there is no serious substrate interference, and no quench steps are required, confirming the feasibility and reliability of the method. Using this method, we successfully quantified 15 types of SCFAs in fecal samples from hepatocellular carcinoma patients and healthy individuals; among these, propionate, butyrate, isobutyrate, and 2-methylbutyrate were significantly decreased in the hepatocellular carcinoma group compared with the healthy control group. These results indicate that the integrated LC-MS metabolomics with isotope-free and dual derivatization is an efficient approach for quantifying FFAs, which may be useful for identifying lipid biomarkers of cancer.Jiangang ZhangShuai YangJingchun WangYanquan XuHuakan ZhaoJuan LeiYu ZhouYu ChenLei WuMingyue ZhouYan LiYongsheng LiElsevierarticleFFAsshort-chain FAsLC-MSisotope-freederivatization2-dimethylaminoethylamineBiochemistryQD415-436ENJournal of Lipid Research, Vol 62, Iss , Pp 100143- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	FFAs short-chain FAs LC-MS isotope-free derivatization 2-dimethylaminoethylamine Biochemistry QD415-436
spellingShingle	FFAs short-chain FAs LC-MS isotope-free derivatization 2-dimethylaminoethylamine Biochemistry QD415-436 Jiangang Zhang Shuai Yang Jingchun Wang Yanquan Xu Huakan Zhao Juan Lei Yu Zhou Yu Chen Lei Wu Mingyue Zhou Yan Li Yongsheng Li Integrated LC-MS metabolomics with dual derivatization for quantification of FFAs in fecal samples of hepatocellular carcinoma patients
description	FFAs display pleiotropic functions in human diseases. Short-chain FAs (SCFAs), medium-chain FAs, and long-chain FAs are derived from different origins, and precise quantification of these FFAs is critical for revealing their roles in biological processes. However, accessing stable isotope-labeled internal standards is difficult, and different chain lengths of FFAs challenge the chromatographic coverage. Here, we developed a metabolomics strategy to analyze FFAs based on isotope-free LC-MS-multiple reaction monitoring integrated with dual derivatization. Samples and dual derivatization internal standards were synthesized using 2-dimethylaminoethylamine or dansyl hydrazine as a “light” label and N,N-diethyl ethylene diamine or N,N-diethyldansulfonyl hydrazide as a “heavy” label under mild and efficient reaction conditions. General multiple reaction monitoring parameters were designed to analyze these FFAs. The limit of detection of SCFAs varied from 0.5 to 3 nM. Furthermore, we show that this approach exhibits good linearity (R2 = 0.99374–0.99929), there is no serious substrate interference, and no quench steps are required, confirming the feasibility and reliability of the method. Using this method, we successfully quantified 15 types of SCFAs in fecal samples from hepatocellular carcinoma patients and healthy individuals; among these, propionate, butyrate, isobutyrate, and 2-methylbutyrate were significantly decreased in the hepatocellular carcinoma group compared with the healthy control group. These results indicate that the integrated LC-MS metabolomics with isotope-free and dual derivatization is an efficient approach for quantifying FFAs, which may be useful for identifying lipid biomarkers of cancer.
format	article
author	Jiangang Zhang Shuai Yang Jingchun Wang Yanquan Xu Huakan Zhao Juan Lei Yu Zhou Yu Chen Lei Wu Mingyue Zhou Yan Li Yongsheng Li
author_facet	Jiangang Zhang Shuai Yang Jingchun Wang Yanquan Xu Huakan Zhao Juan Lei Yu Zhou Yu Chen Lei Wu Mingyue Zhou Yan Li Yongsheng Li
author_sort	Jiangang Zhang
title	Integrated LC-MS metabolomics with dual derivatization for quantification of FFAs in fecal samples of hepatocellular carcinoma patients
title_short	Integrated LC-MS metabolomics with dual derivatization for quantification of FFAs in fecal samples of hepatocellular carcinoma patients
title_full	Integrated LC-MS metabolomics with dual derivatization for quantification of FFAs in fecal samples of hepatocellular carcinoma patients
title_fullStr	Integrated LC-MS metabolomics with dual derivatization for quantification of FFAs in fecal samples of hepatocellular carcinoma patients
title_full_unstemmed	Integrated LC-MS metabolomics with dual derivatization for quantification of FFAs in fecal samples of hepatocellular carcinoma patients
title_sort	integrated lc-ms metabolomics with dual derivatization for quantification of ffas in fecal samples of hepatocellular carcinoma patients
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/fa1702e85bf54cc18f43a00139967ce1
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Integrated LC-MS metabolomics with dual derivatization for quantification of FFAs in fecal samples of hepatocellular carcinoma patients

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