PMID- 31103167
OWN - NLM
STAT- MEDLINE
DCOM- 20190621
LR  - 20190621
IS  - 1873-4324 (Electronic)
IS  - 0003-2670 (Linking)
VI  - 1070
DP  - 2019 Sep 6
TI  - Stable isotope labeling combined with liquid chromatography-tandem mass 
      spectrometry for comprehensive analysis of short-chain fatty acids.
PG  - 51-59
LID - S0003-2670(19)30430-1 [pii]
LID - 10.1016/j.aca.2019.04.021 [doi]
AB  - Short-chain fatty acids (SCFAs) are one class of bacterial metabolites mainly 
      formed by gut microbiota from undigested fibers and proteins. These molecules are 
      able to mediate signal conduction processes of cells, acting as G protein-coupled 
      receptors (GPR) activators and histone deacetylases (HDAC) inhibitors. It was 
      reported that SCFAs were closely associated with various human diseases. However, 
      it is still challenging to analyze SCFAs because of their diverse structures and 
      broad range of concentrations. In this study, we developed a highly sensitive 
      method for simultaneous detection of 34 SCFAs by stable isotope labeling coupled 
      with ultra-high performance liquid chromatography-electrospray ionization-mass 
      spectrometry (UHPLC-ESI-MS/MS) analysis. In this respect, a pair of isotope 
      labeling reagents, N-(4-(aminomethyl)benzyl)aniline (4-AMBA) and 
      N-(4-(aminomethyl)benzyl)aniline-d(5) (4-AMBA-d(5)), were synthesized to label 
      SCFAs from the feces of mice and SCFA standards, respectively. The 4-AMBA-d(5) 
      labeled SCFAs were used as internal standards to compensate the ionization 
      variances resulting from matrix effect and thus minimize quantitation deviation 
      in MS detection. After 4-AMBA labeling, the retention of SCFAs on the 
      reversed-phase column increased and the separation resolution of isomers were 
      improved. In addition, the MS responses of most SCFAs were enhanced by up to 
      three orders of magnitude compared to unlabeled SCFAs. The limits of detection 
      (LODs) of SCFAs were as low as 0.005 ng/mL. Moreover, good linearity for 34 SCFAs 
      was obtained with the coefficient of determination (R(2)) ranging from 0.9846 to 
      0.9999 and the intra- and inter-day relative standard deviations (RSDs) were 
      <17.8% and 15.4%, respectively, indicating the acceptable reproducibility of the 
      developed method. Using the developed method, we successfully quantified 21 SCFAs 
      from the feces of mice. Partial least squares discriminant analysis (PLS-DA) and 
      t-test analysis showed that the contents of 9 SCFAs were significantly different 
      between Alzheimer's disease (AD) and wide type (WT) mice fecal samples. Compared 
      to WT mice, the contents of propionic acid, isobutyric acid, 3-hydroxybutyric 
      acid, and 3-hydroxyisocaleric acid were decreased in AD mice, while lactic acid, 
      2-hydroxybutyric acid, 2-hydroxyisobutyric acid, levulinic acid, and valpronic 
      acid were increased in AD mice. These significantly changed SCFAs in the feces of 
      AD mice may afford to a better understanding of the pathogenesis of AD. Taken 
      together, the developed UHPLC-ESI-MS/MS method could be applied for the sensitive 
      and comprehensive determination of SCFAs from complex biological samples.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Zheng, Jie
AU  - Zheng J
AD  - Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of 
      Education), Department of Chemistry, Wuhan University, Wuhan 430072, PR China.
FAU - Zheng, Shu-Jian
AU  - Zheng SJ
AD  - Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of 
      Education), Department of Chemistry, Wuhan University, Wuhan 430072, PR China.
FAU - Cai, Wen-Jing
AU  - Cai WJ
AD  - Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of 
      Education), Department of Chemistry, Wuhan University, Wuhan 430072, PR China.
FAU - Yu, Lei
AU  - Yu L
AD  - Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of 
      Education), Department of Chemistry, Wuhan University, Wuhan 430072, PR China.
FAU - Yuan, Bi-Feng
AU  - Yuan BF
AD  - Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of 
      Education), Department of Chemistry, Wuhan University, Wuhan 430072, PR China.
FAU - Feng, Yu-Qi
AU  - Feng YQ
AD  - Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of 
      Education), Department of Chemistry, Wuhan University, Wuhan 430072, PR China. 
      Electronic address: yqfeng@whu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20190411
PL  - Netherlands
TA  - Anal Chim Acta
JT  - Analytica chimica acta
JID - 0370534
RN  - 0 (Fatty Acids, Volatile)
SB  - IM
MH  - Animals
MH  - Chromatography, High Pressure Liquid
MH  - Fatty Acids, Volatile/*analysis
MH  - Gastrointestinal Microbiome
MH  - Humans
MH  - *Isotope Labeling
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Molecular Structure
MH  - Tandem Mass Spectrometry
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Liquid chromatography-tandem mass spectrometry
OT  - Quantification
OT  - Short-chain fatty acids
OT  - Stable isotope labeling
EDAT- 2019/05/20 06:00
MHDA- 2019/06/22 06:00
CRDT- 2019/05/20 06:00
PHST- 2019/02/23 00:00 [received]
PHST- 2019/04/06 00:00 [revised]
PHST- 2019/04/09 00:00 [accepted]
PHST- 2019/05/20 06:00 [entrez]
PHST- 2019/05/20 06:00 [pubmed]
PHST- 2019/06/22 06:00 [medline]
AID - S0003-2670(19)30430-1 [pii]
AID - 10.1016/j.aca.2019.04.021 [doi]
PST - ppublish
SO  - Anal Chim Acta. 2019 Sep 6;1070:51-59. doi: 10.1016/j.aca.2019.04.021. Epub 2019 
      Apr 11.