title: Simultaneous determination of amino acids and neurotransmitters in plasma samples from schizophrenic patients by hydrophilic interaction liquid chromatography with tandem mass spectrometry.
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.
authors.affiliation: Departamento de Química, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Diego Soares
authors.initials: DS
authors.lastname: Domingues
authors.forename: Eduardo José
authors.initials: EJ
authors.lastname: Crevelin
authors.forename: Luiz Alberto Beraldo
authors.initials: LA
authors.lastname: de Moraes
authors.forename: Jaime Eduardo
authors.initials: JE
authors.lastname: Cecilio Hallak
authors.forename: José Alexandre
authors.initials: JA
authors.lastname: de Souza Crippa
authors.forename: Maria Eugênia
authors.initials: ME
authors.lastname: Costa Queiroz
mesh_terms: D000596:Amino Acids / Q000097:blood* / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D057230:Limit of Detection; D008297:Male; D018377:Neurotransmitter Agents / Q000097:blood* / Q000737:chemistry; D012559:Schizophrenia / Q000097:blood*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000596:Amino Acids; D018377:Neurotransmitter Agents
keywords: Amino acids; Hydrophilic interaction; Neurotransmitters; Plasma samples; Schizophrenia