Early diagnosis of dopamine and serotonin metabolic defects is of importance notably because of the availability of therapeutic strategies able to prevent the associated progressive brain dysfunction. The diagnosis of these diseases relies on the determination of monoamine metabolites and pterins in cerebrospinal fluid (CSF). Current methods involve at least two high-performance liquid chromatography runs of CSF analysis. The first one is devoted to the quantification of dopamine and serotonin metabolites and the second one to the quantification of pterins. Here, we describe a single-step method to measure monoamine neurotransmitter metabolites and pterins of interest in less than 10 min by ultrahigh-performance liquid chromatography coupled to sequential coulometric oxidation and fluorescence detections. All target compounds were quantified in CSF with a small volume (50 μL) and a single filtration step for sample preparation and analysis. After validation, the proposed method was applied to the determination of age-related reference ranges in the CSF of target compounds from a series of 1372 samples collected in France from 2008 to 2014. In the same period, the results obtained for 19 CSF samples from patients with known neurotransmitter disorders and 115 CSF samples with known immune system activation confirmed the expected pattern of changes in monoamine metabolites and pterins.

中文翻译：

---

多巴胺和5-羟色胺代谢紊乱的单步快速诊断

多巴胺和5-羟色胺代谢缺陷的早期诊断具有重要意义，特别是因为有能够预防相关的进行性脑功能障碍的治疗策略。这些疾病的诊断取决于脑脊液（CSF）中单胺代谢产物和蝶呤的测定。当前的方法涉及至少两次CSF分析的高效液相色谱分析。第一个致力于多巴胺和5-羟色胺代谢产物的定量，第二个致力于蝶呤的定量。在这里，我们描述了一种单步方法，通过超高效液相色谱与顺序库仑氧化和荧光检测相结合，可在不到10分钟的时间内测量单胺神经递质代谢物和感兴趣的蝶呤。所有目标化合物均在CSF中以小体积（50μL）进行定量，并且仅需一个过滤步骤即可进行样品制备和分析。验证后，该方法用于确定目标化合物CSF中年龄相关的参考范围，这些化合物来自于2008年至2014年在法国收集的一系列1372个样品中。同期，从19个CSF样品中获得了结果患有已知神经递质疾病的患者和具有已知免疫系统激活作用的115份CSF样品证实了单胺代谢产物和蝶呤变化的预期模式。