High speed quantitative UPLC-MS analysis of multiple amines in human plasma and serum via pre-column derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate: Application to acetaminophen-induced liver failure

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Title: High speed quantitative UPLC-MS analysis of multiple amines in human plasma and serum via pre-column derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate: Application to acetaminophen-induced liver failure
Author(s): Gray, N
Zia, R
King, A
Patel, VC
Wendon, J
McPhail, MJW
Coen, M
Plumb, RS
Wilson, ID
Nicholson, JK
Item Type: Journal Article
Abstract: A targeted reversed-phase gradient UPLC-MS/MS assay has been developed for the quantification/monitoring of amino acids and amino-containing compounds in human plasma and serum using pre-column derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AccQTag UltraTM). Derivatization of the target amino-containing compounds reagent required minimal sample preparation and resulted in analytes with excellent chromatographic and mass spectrometric properties. The resulting method, which requires only 10 µl of sample, provides the reproducible and robust separation of 66 analytes in 7.5 minutes, including baseline resolution of isomers such as e.g. leucine and isoleucine. The assay has been validated for the quantification of 33 amino compounds (predominantly amino acids) over a concentration range from 2-20 and 800µM. Intra- and inter-day accuracy of between 0.05-15.6 and 0.78 -13.7 % and precision between 0.91-16.9 % and 2.12-15.9 % were obtained. A further 33 biogenic amines can be monitored in samples for relative changes in concentration rather than quantification. Application of the assay to samples derived from healthy controls and patients suffering from acetaminophen (APAP, paracetamol) induced acute liver failure (ALF) showed significant differences in the amounts of aromatic and branched chain amino acids between the groups as well as a number of other analytes, including the novel observation of increased concentrations of sarcosine in ALF patients. The properties of the developed assay, including short analysis time, make it suitable for high throughput targeted UPLC-ESI-MS/MS metabonomic analysis in clinical and epidemiological environments.
Date of Acceptance: 19-Jan-2017
URI: http://hdl.handle.net/10044/1/44168
ISSN: 1520-6882
Publisher: American Chemical Society
Journal / Book Title: Analytical Chemistry
Copyright Statement: This paper is embargoed until publication. Once published will be available fully open access.
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: MC_PC_12025
Keywords: Analytical Chemistry
0301 Analytical Chemistry
0904 Chemical Engineering
0399 Other Chemical Sciences
Publication Status: Accepted
Embargo Date: publication subject to indefinite embargo
Appears in Collections:Division of Surgery
Faculty of Medicine



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