Quantification of endogenous neurotransmitters and related compounds by liquid chromatography coupled to tandem mass spectrometry

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• dc.contributor.author Olesti Muñoz, Eulàlia, 1991-ca
• dc.contributor.author Rodríguez-Morató, Jose, 1987-ca
• dc.contributor.author Gomez-Gomez, Àlexca
• dc.contributor.author Ramaekers, Johannes G.ca
• dc.contributor.author Torre Fornell, Rafael de laca
• dc.contributor.author Pozo Mendoza, Óscar J., 1975-ca
• dc.date.accessioned 2018-10-09T10:46:02Z
• dc.date.issued 2019
• dc.description.abstract Neurotransmitters are signaling molecules, playing key roles in neuronal communications in the brain. Drug induced changes in neurotransmitters and other brain metabolite concentration may be used to characterize drugs according to their targeted metabolomics profile. Here, we report the development and validation of a straightforward liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of 16 endogenous small polar compounds in rat plasma and brain homogenates. The method enables the quantification of the neurotransmitters γ-aminobutyric acid, glutamate, acetylcholine and adenosine, as well as choline, glutamine, acetylcarnitine, carnitine, creatine, creatinine, valine, leucine, isoleucine, phenylalanine, tyrosine and tryptophan. After optimizing the sample preparation, chromatographic and spectrometric conditions, the method was successfully validated using the standard addition approach and a hydrophilic interaction chromatography (HILIC) with an amide column. The method was shown to be linear (r > 0.99) as all the compounds were within the ±25% values of intra and inter-day precision and accuracy acceptance. A matrix effect was corrected with the use of 10 isotopically labelled internal standards and the compound stability was evaluated for all compounds. Relevant exaltation of choline (in plasma) and creatinine (in brain) were solved with −20 °C conditions. The applicability of the method was tested by evaluating brain alterations in the concentrations of neurotransmitters and related compounds after the administration of two psychostimulant drugs of abuse (cocaine and methylenedioxypyrovalerone) to rats. A neuro-metabolic fingerprint of each drug was obtained that reflected their pharmacological profile. Altogether, this methodology presents a valuable targeted metabolomics tool for basic and clinical research studies.
• dc.description.sponsorship This work was supported by the European Commission (Drugs Policy Initiatives, Justice Programme 2014–2020, contract n°. HOME/2014/JDRU/AG/DRUG/7082, Predicting Risk of Emerging Drugs with In silico and Clinical Toxicology). JRM is acknowledged for the EU's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant No. 712949 (TECNIOspring PLUS) from the Agency for Business Competitiveness of the Government of Catalonia. The Spanish Health National System is also acknowledged for the contract of OJP (CPII16/00027)
• dc.format.mimetype application/pdf
• dc.identifier.citation Eulàlia Olesti, Jose Rodríguez-Morató, Alex Gomez-Gomez, Johannes G. Ramaekers, Rafael de la Torre, Oscar J. Pozoa. Quantification of endogenous neurotransmitters and related compounds by liquid chromatography coupled to tandem mass spectrometry. Talanta. 2019 Jan; 192: 93-102. DOI: 10.1016/j.talanta.2018.09.034
• dc.identifier.doi http://dx.doi.org/10.1016/j.talanta.2018.09.034
• dc.identifier.issn 0039-9140
• dc.identifier.uri http://hdl.handle.net/10230/35587
• dc.language.iso eng
• dc.publisher Elsevierca
• dc.relation.ispartof Talanta. 2019 Jan;192:93-102
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/712949
• dc.rights © Elsevier http://dx.doi.org/10.1016/j.talanta.2018.09.034
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.other Neurotransmissors
• dc.subject.other Cromatografia de líquids
• dc.subject.other Espectrometria de masses
• dc.title Quantification of endogenous neurotransmitters and related compounds by liquid chromatography coupled to tandem mass spectrometryca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion