title: High-Speed Quantitative UPLC-MS Analysis of Multiple Amines in Human Plasma and Serum via Precolumn Derivatization with 6-Aminoquinolyl-N-hydroxysuccinimidyl Carbamate: Application to Acetaminophen-Induced Liver Failure.
abstract: A targeted reversed-phase gradient UPLC-MS/MS assay has been developed for the quantification /monitoring of 66 amino acids and amino-containing compounds in human plasma and serum using precolumn derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AccQTag Ultra). Derivatization of the target amines required minimal sample preparation and resulted in analytes with excellent chromatographic and mass spectrometric detection properties. The resulting method, which requires only 10 μL of sample, provides the reproducible and robust separation of 66 analytes in 7.5 min, including baseline resolution of isomers such as leucine and isoleucine. The assay has been validated for the quantification of 33 amino compounds (predominantly amino acids) over a concentration range from 2 to 20 and 800 μM. Intra- and interday accuracy of between 0.05 and 15.6 and 0.78-13.7% and precision between 0.91 and 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.
authors.affiliation: Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London , South Kensington, London SW7 2AZ, United Kingdom.
authors.forename: Nicola
authors.initials: N
authors.lastname: Gray
authors.affiliation: Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London , South Kensington, London SW7 2AZ, United Kingdom.
authors.forename: Rabiya
authors.identifier: 0000-0003-2407-3936
authors.initials: R
authors.lastname: Zia
authors.affiliation: Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London , South Kensington, London SW7 2AZ, United Kingdom.
authors.forename: Adam
authors.initials: A
authors.lastname: King
authors.affiliation: Institute of Liver Studies and Transplantation, Kings College Hospital , Denmark Hill, London SE5 9RS, United Kingdom.
authors.forename: Vishal C
authors.initials: VC
authors.lastname: Patel
authors.affiliation: Institute of Liver Studies and Transplantation, Kings College Hospital , Denmark Hill, London SE5 9RS, United Kingdom.
authors.forename: Julia
authors.initials: J
authors.lastname: Wendon
authors.affiliation: Institute of Liver Studies and Transplantation, Kings College Hospital , Denmark Hill, London SE5 9RS, United Kingdom.
authors.forename: Mark J W
authors.initials: MJ
authors.lastname: McPhail
authors.affiliation: Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London , South Kensington, London SW7 2AZ, United Kingdom.
authors.forename: Muireann
authors.initials: M
authors.lastname: Coen
authors.affiliation: Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London , South Kensington, London SW7 2AZ, United Kingdom.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Plumb
authors.affiliation: Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London , South Kensington, London SW7 2AZ, United Kingdom.
authors.forename: Ian D
authors.identifier: 0000-0002-8558-7394
authors.initials: ID
authors.lastname: Wilson
authors.affiliation: Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London , South Kensington, London SW7 2AZ, United Kingdom.|MRC-NIHR National Phenome Centre, Division of Computational and Systems Medicine, Department of Surgery and Cancer, IRDB Building, Imperial College London, Hammersmith Hospital , London W12 0NN, United Kingdom.
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
mesh_terms: D000082:Acetaminophen / Q000633:toxicity; D000328:Adult; D000588:Amines / Q000097:blood* / Q000737:chemistry; D000596:Amino Acids / Q000032:analysis; D000634:Aminoquinolines / Q000737:chemistry*; D002219:Carbamates / Q000737:chemistry*; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D057230:Limit of Detection; D008297:Male; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: C078178:6-aminoquinolyl-N-hydroxysuccinimidyl carbamate; D000588:Amines; D000596:Amino Acids; D000634:Aminoquinolines; D002219:Carbamates; D000082:Acetaminophen