A versatile method was developed and validated for simultaneous determination of the monoamine neurotransmitters (MNT) dopamine (DA), 3–4-dyhydroxyphenilacetic acid (DOPAC), homovanilic acid (HVA), serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) in rat brain microdialysate samples using high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS). The method allowed for small sample volume, using positive and negative ionization mode in a single run analysis without any derivatization or cleanup steps. Analytes were quantified at concentrations ranging from 100 ng/mL to 0.05, 10, 0.5, 0.1 or 1 ng/mL (lower limit of quantification, LLOQ) of DA, DOPAC, HVA, 5-HT and 5-HIAA, respectively, showing linearity (r > 0.98), accuracy, and precision (R.S.D ± 15%) according to validation limits accepted by international guidelines. The method was successfully applied for monitoring the concentration changes of MNT in microdialysate samples from medium prefrontal cortex of Wistar rats in a neurodevelopmental model of schizophrenia before and after quetiapine 5 mg/kg i.v. bolus dose administration. No alterations in MNTs were observed in schizophrenia phenotyped rats (SPR) in comparison to the baseline shading a light on the limited response rate to antipsychotic drugs observed in chronic schizophrenic patients.

开发了一种通用的方法，该方法可同时测定单胺神经递质（MNT）多巴胺（DA），3–4-二羟基苯乙酸（DOPAC），高香草酸（HVA），5-羟色胺（5-HT）和5-羟基吲哚乙酸（使用高效液相色谱串联质谱（LC-MS / MS）在大鼠脑微透析液样品中添加5-HIAA）。该方法可在不进行任何衍生化或纯化步骤的情况下，在一次运行分析中使用正电离和负电离模式，实现较小的样品量。分析物的浓度分别为DA，DOPAC，HVA，5-HT和5-HIAA的浓度范围为100 ng / mL至0.05、10、0.5、0.1或1 ng / mL（定量下限，LLOQ），显示线性（r> 0.98），准确度和精密度（RSD±15％）根据国际准则接受的验证极限。推注剂量给药。与基线阴影相比，在精神分裂症表型大鼠（SPR）中未观察到MNT的改变，这说明在慢性精神分裂症患者中对抗精神病药的反应有限。