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.

Simultaneous determination of 4-hydroxyphenyl lactic acid, 4-hydroxyphenyl acetic acid, and 3,4-hydroxyphenyl propionic acid in human urine by ultra-high performance liquid chromatography with fluorescence detection

“…Amino acids play an important role in the process of human metabolism, so they are important substances which are related to human health [1][2][3][4]. Studies have shown that amino acid metabolism diseases and malignant tumors had certain relevance to some tyrosine metabolite [5][6][7][8][9].…”

Simultaneous determination of five essential amino acids in plasma of Hyperlipidemic subjects by UPLC-MS/MS

“…Commonly, hydrophilic interaction chromatography (HILIC) column is widely used to analyze amino acids [18,23,[26][27][28]. HILIC column has hydrophilic polar stationary phase which can interact with highly polar compounds by strong hydrophilic interaction [18].…”

“…Compared with GC-MS and HPLC, liquid chromatography tandem with mass spectrometry detection (LC-MS) had higher sensitivity and stability. So far, there several LC-MS methods have been reported [19][20][21][22][23]. However, some methods were used in food [21,22], some methods had high limits of detection or need derivatization to improve the chromatographic separation [19,20].…”

Targeted metabolomics analysis of aromatic amino acids and their gut microbiota–host cometabolites in rat serum and urine by liquid chromatography coupled with tandem mass spectrometry

“…Recently, hyphenated analytical techniques combining separation technologies with MS have become highly effective tools for small‐molecule analysis. In this regard, methods using LC–MS/MS have been reported for the analysis of several endogenous metabolites from tissue and biological systems . Nevertheless, most of these quantitative methods focus on amino acids or uremic toxins rather than the gut microbiota cometabolic pathways of aromatic amino acids.…”