Investigation on the combined effect of cocaine and ethanol administration through a liquid chromatography-mass spectrometry metabolomics approach
Authors
Sánchez López, Elena; Marcos González, Alberto; Ambrosio, Emilio; Mayboroda, Oleg A.; Marina Alegre, María Luisa; [et al.]Identifiers
Permanent link (URI): http://hdl.handle.net/10017/48161DOI: 10.1016/j.jpba.2017.03.061
ISSN: 0731-7085
Date
2017-06-05Affiliation
Universidad de Alcalá. Departamento de Química Analítica, Química Física e Ingeniería QuímicaBibliographic citation
Journal of Pharmaceutical and Biomedical Analysis, 2017, v. 140, p. 313-321
Keywords
Cocaine
Drug dependence
Ethanol
Metabolomics
Liquid chromatography mass spectrometry
Rat plasma
Project
Instituto de Salud Carlos III, Red Española de Trastornos Adictivos (RTARD12/028/0020) y Plan Nacional de Drogas Abuso (PNSD-2012I057)
Universidad de Alcalá (CCG2014/EXP-059)
info:eu-repo/grantAgreement/MINECO//CTQ2013-48740-P/ES/METODOLOGIAS AVANZADAS PARA ANALISIS QUIRAL MEDIANTE TECNICAS MICROSEPARATIVAS. BUSQUEDA DE BIOMARCADORES EN SISTEMAS ENANTIOSELECTIVOS/
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/publishedVersion
Rights
Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
© Elsevier
Access rights
info:eu-repo/semantics/openAccess
Abstract
Alcohol is the most widely consumed legal drug, whereas cocaine is the illicit psychostimulant most commonly used in Europe. The combined use of alcohol and cocaine is frequent among drug-abuse consumers and leads to further exacerbation of health consequences compared to individual consumption. The pharmacokinetic and metabolic interactions leading to an increase in their combined toxicity still remains poorly understood. Here, the first metabolomics study of combined cocaine and ethanol chronic exposure effects is reported. A Liquid Chromatography strategy based on sample derivatization with 9-fluorenylmethyloxycarbonyl chloride and using a C18 column coupled to high resolution Mass Spectrometry (time of flight analyzer) was employed to analyze plasma from rats exposed intravenously to these drugs in a 52-min analysis. Using a combination of non-supervised and supervised multivariate analysis the metabolic differences between our experimental groups were explored and unraveled. A comparative analysis of the individual models and their variable importance in the projection values have shown that every experiment intervention includes a subset of specific metabolites. Eleven of these metabolites were annotated, where eight were unequivocally identified using standards and three were tentatively identified by matching the MS/MS spectra to libraries. The results demonstrated that the affected metabolic pathways were mainly those related to the metabolism of different amino acids. (C) 2017 Elsevier B.V. All rights reserved.
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