Merged Targeted Quantification and Untargeted Profiling for Comprehensive Assessment of Acylcarnitine and Amino Acid Metabolism.

Details

Serval ID
serval:BIB_EFE8F1130539
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Merged Targeted Quantification and Untargeted Profiling for Comprehensive Assessment of Acylcarnitine and Amino Acid Metabolism.
Journal
Analytical chemistry
Author(s)
Teav T. (co-first), Gallart-Ayala H. (co-first), van der Velpen V., Mehl F., Henry H. (co-last), Ivanisevic J. (co-last)
ISSN
1520-6882 (Electronic)
ISSN-L
0003-2700
Publication state
Published
Issued date
17/09/2019
Peer-reviewed
Oui
Volume
91
Number
18
Pages
11757-11769
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Acylcarnitines and amino acids are key players in energy metabolism; however, analytical methods for comprehensive and straightforward quantitative profiling of these metabolites, without derivatization or use of ion-pairing agents, are lacking. We therefore developed a hydrophilic interaction chromatography (HILIC)-based high-resolution mass spectrometry (HRMS) method for the simultaneous quantification of acylcarnitines and amino acids in a single run, while taking advantage of HRMS data acquired in full-scan mode to screen for additional derivatives and other polar metabolites. A single-step metabolite extraction with internal standard mixture (in methanol) warranted high-throughput sample preparation whose applicability was demonstrated on a panel of human biofluids (i.e., blood plasma, CSF, and urine) and brain tissue. Method accuracy was within 90-106% of validated NIST reference plasma concentrations for the panel of measured amino acids. Amino acid and acylcarnitine extraction recoveries were 87-100% on average, depending on the concentration range spiked. The coefficient of variation (CV) was 1-10% and 1-25% for intra- and interday measurements, respectively, with the highest CVs for the metabolites at the limit of quantification, depending on the biofluid. Acylcarnitine and amino acid signatures or chemical composition barcodes of the different biofluids and human brain tissue were acquired and biofluid- and tissue-associated differences were discussed in the context of their respective physiological roles. Significant differences were observed in the amino acid profiles, whereas acylcarnitine composition did not show biofluid-characteristic or brain region-specific pattern. The retrospective exploration of full-scan all-ion-fragmentation data allowed us to extract the information on unsaturated and hydroxylated acylcarnitine species, amines, and purine and pyrimidine metabolites. This merged targeted and untargeted approach provides an innovative strategy for simultaneous and comprehensive assessment of acylcarnitine and amino acid metabolism in clinical research studies using relevant biofluids and tissue extracts.
Keywords
acylcarnitines, amino acids, HILIC-MS, targeted and integrated metabolomics, energy metabolism, metabolic barcodes
Pubmed
Web of science
Funding(s)
Fondation Pierre Mercier pour la science
Create date
16/09/2019 21:53
Last modification date
10/12/2019 7:17
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