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Simultaneous determination of 30 neurologically and metabolically important molecules: A sensitive and selective way to measure tyrosine and tryptophan pathway metabolites and other biomarkers in human serum and cerebrospinal fluid
Journal of Chromatography A ( IF 4.1 ) Pub Date : 2020-12-02 , DOI: 10.1016/j.chroma.2020.461775
Zsolt Galla , Cecília Rajda , Gábor Rácz , Nóra Grecsó , Ákos Baráth , László Vécsei , Csaba Bereczki , Péter Monostori

Concurrent measurement of tyrosine, tryptophan and their metabolites, and other co-factors could help to diagnose and better understand a wide range of metabolic and neurological disorders. The two metabolic pathways are closely related to each other through co-factors, regulator molecules and enzymes. By using high performance liquid chromatography coupled to electrospray ionization triple quadrupole mass spectrometry, we present a robust, selective and comprehensive method to determine 30 molecules within 20 min using a Waters Atlantis dC18. The method was validated according to the guideline of European Medicines Agency on bioanalytical method validation. Analytical performance met all the EMA requirements and the assay covered the relevant clinical concentrations. Linear correlation coefficients were all >0.998. Intra-day and inter-day accuracy were between 80-119% and 81-117%, precision 1-19% respectively. The method was applied to measure TYR, TRP and their metabolites, and other neurologically important molecules in human serum and CSF samples. The assay can facilitate the diagnosis and is suitable for determination of reference values in clinical laboratories.



中文翻译:

同时测定30种神经和代谢重要分子:测定人血清和脑脊液中酪氨酸和色氨酸途径代谢物及其他生物标记物的灵敏且选择性的方法

同时测定酪氨酸,色氨酸及其代谢产物和其他辅助因子可以帮助诊断和更好地理解各种代谢和神经系统疾病。这两个代谢途径通过辅因子,调节分子和酶彼此密切相关。通过将高效液相色谱与电喷雾电离三重四极杆质谱联用,我们提出了一种可靠,选择性和全面的方法,使用沃特世Atlantis dC18在20分钟内测定30个分子。该方法已根据欧洲药品管理局有关生物分析方法验证的指南进行了验证。分析性能满足所有EMA要求,并且分析涵盖了相关的临床浓度。线性相关系数均> 0.998。日内和日间准确度分别在80-119%和81-117%之间,精确度在1-19%之间。该方法用于测定人血清和脑脊液样品中的TYR,TRP及其代谢产物以及其他神经学上重要的分子。该测定法可以促进诊断并且适合于在临床实验室中确定参考值。

更新日期:2020-12-07
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