Analytical and Bioanalytical Chemistry

, Volume 410, Issue 6, pp 1735–1748 | Cite as

Comprehensive characterization of neurochemicals in three zebrafish chemical models of human acute organophosphorus poisoning using liquid chromatography-tandem mass spectrometry

  • Cristian Gómez-Canela
  • Daniel Tornero-Cañadas
  • Eva Prats
  • Benjamí Piña
  • Romà Tauler
  • Demetrio Raldúa
Research Paper


There is a growing interest in biological models to investigate the effect of neurotransmitter dysregulation on the structure and function of the central nervous system (CNS) at different stages of development. Zebrafish, a vertebrate model increasingly used in neurobiology and neurotoxicology, shares the common neurotransmitter systems with mammals, including glutamate, GABA, glycine, dopamine, norepinephrine, epinephrine, serotonin, acetylcholine, and histamine. In this study, we have evaluated the performance of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the multiresidue determination of neurotransmitters and related metabolites. In a first step, ionization conditions were tested in positive electrospray mode and optimum fragmentation patterns were determined to optimize two selected reaction monitoring (SRM) transitions. Chromatographic conditions were optimized considering the chemical structure and chromatographic behavior of the analyzed compounds. The best performance was obtained with a Synergy Polar-RP column, which allowed the separation of the 38 compounds in 30 min. In addition, the performance of LC-MS/MS was studied in terms of linearity, sensitivity, intra- and inter-day precision, and overall robustness. The developed analytical method was able to quantify 27 of these neurochemicals in zebrafish chemical models for mild (P1), moderate (P2), and severe (P3) acute organophosphorus poisoning (OPP). The results show a general depression of synaptic-related neurochemicals, including the excitatory and inhibitory amino acids, as well as altered phospholipid metabolism, with specific neurochemical profiles associated to the different grades of severity. These results confirmed that the developed analytical method is a new tool for neurotoxicology research using the zebrafish model.


Neurotransmitters LC-MS/MS Quality parameters Zebrafish larvae Animal models of human disease Acute organophosphorus poisoning 



The research leading to these results has received funding from the European Research Council under European Union's Seven Framework Programme (FP/2007e2013)/ERC Grant Agreement n.320737, the NATO SfP project MD.SFPP 984777, and the grant CTM 2014-51985 from the Spanish Ministry of Economy, Industry and Competitiveness. Moreover, Rita Bausano is acknowledged for extraction samples support during her Erasmus Traineeship stage in the Environmental Chemistry Department at IDEA-CSIC (Barcelona, Spain).

Compliance with Ethical Standards

Conflict of interest

The authors declare no financial conflict of interest.

Supplementary material

216_2017_827_MOESM1_ESM.pdf (1.8 mb)
ESM 1 (PDF 1.78 mb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Cristian Gómez-Canela
    • 1
  • Daniel Tornero-Cañadas
    • 1
  • Eva Prats
    • 2
  • Benjamí Piña
    • 1
  • Romà Tauler
    • 1
  • Demetrio Raldúa
    • 1
  1. 1.Department of Environmental Chemistry, IDAEA-CSICBarcelonaSpain
  2. 2.Centre d’Investigació i Desenvolupament, CID-CSICBarcelonaSpain

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