Stable isotope labeling derivatization and magnetic dispersive solid phase extraction coupled with UHPLC-MS/MS for the measurement of brain neurotransmitters in post-stroke depression rats administrated with gastrodin
Stable isotope labeling derivatization and magnetic dispersive solid phase extraction coupled with UHPLC-MS/MS for the measurement of brain neurotransmitters in post-stroke depression rats administrated with gastrodin
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稳定同位素标记衍生化和磁分散固相萃取联合 UHPLC-MS/MS 测定天麻素脑卒中后抑郁大鼠的脑神经递质
DOI：
10.1016/j.aca.2018.11.011
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发表时间：
2019-03-21
影响因子：
6.2
通讯作者：
Liu, Huwei
中科院分区：
文献类型：
--
作者：
Zhao, Xian-En;He, Yongrui;Liu, Huwei
通过双位点在体微透析技术同步检测脑内神经递质和血液药物代谢，可以为脑卒中后抑郁症（PSD）等神经系统疾病提供非常重要的信息。本工作首次设计、合成了d（0）/d（3）-6-N-甲基罗丹明6 G-N-羟基琥珀酰亚胺甲酸酯（d（0）/d（3）-MRSF），并将其作为稳定同位素标记衍生化试剂用于超高效液相色谱-串联质谱法测定多种神经递质。轻d（0）-MRSF用于标记真实的样品中的神经递质，重d（3）-MRSF用于标记标准品，其用作定量的内标以最小化基质效应。d（0）/d（3）-MRSF-神经递质衍生物很容易吸附在Fe3O4 @石墨烯氧化物表面。建立了磁分散固相萃取-稳定同位素标记衍生化技术用于样品前处理的方法。d（0）/d（3）-MRSF的永久正电荷部分显著增强神经递质的电离效率。结果表明，在相同的仪器条件下，合成的MRSF衍生化方法的检测灵敏度比市售的丹磺酰氯方法高几十到几百倍。d（0）-和d（3）-MRSF标记的神经递质的特异性和规则性子离子m/z分别为413.3和416.3，m/z分别为429.4和432.4。检测限为2.0-40.0 pM。准确度范围为92.3%至108.2%，日内和日间精密度范围为2.2%至12.8%。同步动态测定PSD大鼠脑内神经递质和血中天麻素的浓度变化。结果表明，天麻素对脑内神经递质的调节作用与临床治疗PSD的药物氟西汀相似。总之，所开发的方法被证明是有前途的灵敏，准确和同时测定多种神经递质的微量生物流体。(C)2018爱思唯尔B. V.保留所有权利。
Synchronous measurement of brain neurotransmitters and blood drug metabolism by dual sites in vivo microdialysis can provide very important information for several neurological disorders such as post-stroke depression (PSD). In this work, d(0)/d(3)-6-N-methyl-rhodamine 6G-N-hydroxysuccinimidyl formate (d(0)/d(3)-MRSF) were firstly designed, synthesized and used as stable isotope labeling derivatization reagents for the determination of multiple neurotransmitters by ultra-high performance liquid chromatography-tandem mass spectrometry. The light d(0)-MRSF was used to label neurotransmitters in real samples and the heavy d(3)-MRSF was used to label standards, which served as internal standards for quantification to minimize matrix effect. The d(0)/d(3)-MRSF-neurotransmitter derivatives were easily adsorbed onto the surface of Fe3O4@graphene oxide. Magnetic dispersive solid phase extraction followed with stable isotope labeling derivatization was developed for efficient sample pretreatment. The permanent positively charged moiety of d(0)/d(3)-MRSF significantly enhanced the ionization efficiency of neurotransmitters. The comparison results indicated that the synthesized MRSF derivatization method can bring better detection sensitivity than the commercial dansyl chloride method about tens to hundreds of times on the same instrumentation. Specific and regular product ions of m/z 413.3 and 416.3, m/z 429.4 and 432.4 were observed for d(0)-and d(3)-MRSF labeled neurotransmitters, respectively. The limits of detection were in the range of 2.0-40.0 pM. The accuracies ranged from 92.3% to 108.2% with the intra- and inter-day precisions in the range of 2.2-12.8%. Synchronous and dynamic determination of concentrations changes of brain neurotransmitters and blood gastrodin of PSD rats was achieved. The results indicated that gastrodin had analogous regulating effect of brain neurotransmitter, which like the clinical medicine fluoxetine of PSD. Taken together, the developed method was demonstrated to be promising for sensitive, accurate and simultaneous determination of multiple neurotransmitters in trace biofluids. (C) 2018 Elsevier B.V. All rights reserved.