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Simultaneous determination of amino acids and neurotransmitters in plasma samples from schizophrenic patients by hydrophilic interaction liquid chromatography with tandem mass spectrometry
Authors:Diego Soares Domingues  Eduardo José Crevelin  Luiz Alberto Beraldo de Moraes  Jaime Eduardo Cecilio Hallak  José Alexandre de Souza Crippa  Maria Eugênia Costa Queiroz
Affiliation:1. Departamento de Química, Faculdade de Filosofia Ciências e Letras de Ribeir?o Preto, Universidade de S?o Paulo, S?o Paulo, Brazil;2. Department of Neuroscience and Behavior, Ribeir?o Preto Medical School, University of S?o Paulo, S?o Paulo, Brazil
Abstract:A sensitive, reproducible, and rapid method was developed for the simultaneous determination of underivatized amino acids (aspartate, serine, glycine, alanine, methionine, leucine, tyrosine, and tryptophan) and neurotransmitters (glutamate and γ‐aminobutyric acid) in plasma samples using hydrophilic interaction liquid chromatography coupled to triple quadrupole tandem mass spectrometry. The plasma concentrations of amino acids and neurotransmitters obtained from 35 schizophrenic patients in treatment with clozapine (27 patients) and olanzapine (eight patients) were compared with those obtained from 38 healthy volunteers to monitor the effectiveness of treatment. The chromatographic conditions separated ten target compounds within 3 min. This method presented linear ranges that varied from (lower limit of quantification: 9.7–13.3 nmol/mL) to (upper limit of quantification: 19.4–800 nmol/mL), intra‐ and interassay precision with coefficients of variation lower than 10%, and relative standard error values of the accuracy ranged from –2.1 to 9.9%. The proposed method appropriately determines amino acids and neurotransmitters in plasma from schizophrenic patients. Compared with the control group (healthy volunteers), the plasma levels of methionine in schizophrenic patients treated with olanzapine are statistically significantly higher. Moreover, schizophrenic patients treated with clozapine tend to have increased plasma levels of glutamate.
Keywords:Amino acids  Hydrophilic interaction  Neurotransmitters  Plasma samples  Schizophrenia
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