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J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Jun 1;1054:64-72. doi: 10.1016/j.jchromb.2017.03.039. Epub 2017 Apr 10.

A new combined method of stable isotope-labeling derivatization-ultrasound-assisted dispersive liquid-liquid microextraction for the determination of neurotransmitters in rat brain microdialysates by ultra high performance liquid chromatography tandem mass spectrometry.

Author information

1
Shandong Provincial Key Laboratory of Life-Organic Analysis & Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, PR China.
2
Shandong Provincial Key Laboratory of Life-Organic Analysis & Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, PR China; Key Laboratory of TCM Quality Control Technology, Shandong Analysis and Test Center, Shandong Academy of Sciences, 19 Keyuan Street, Jinan 250014, Shandong, PR China; Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Science, Xining 810001, Qinghai, PR China. Electronic address: xianenzhao@163.com.
3
Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Science, Xining 810001, Qinghai, PR China.
4
Key Laboratory of TCM Quality Control Technology, Shandong Analysis and Test Center, Shandong Academy of Sciences, 19 Keyuan Street, Jinan 250014, Shandong, PR China.
5
Key Laboratory of TCM Quality Control Technology, Shandong Analysis and Test Center, Shandong Academy of Sciences, 19 Keyuan Street, Jinan 250014, Shandong, PR China. Electronic address: wangx@sdas.org.
6
Shandong Provincial Key Laboratory of Life-Organic Analysis & Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, PR China; Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Science, Xining 810001, Qinghai, PR China. Electronic address: jmyou6304@163.com.

Abstract

In this work, for the first time, a new hyphenated technique of stable isotope-labeling derivatization-ultrasound-assisted dispersive liquid-liquid microextraction has been developed for the simultaneous determination of monoamine neurotransmitters (MANTs) and their biosynthesis precursors and metabolites. The developed method was based on ultra high performance liquid chromatography tandem mass spectrometry detection using multiple-reaction monitoring mode. A pair of mass spectrometry sensitizing reagents, d0-10-methyl-acridone-2-sulfonyl chloride and d3-10-methyl-acridone-2-sulfonyl chloride, as stable isotope probes was utilized to facilely label neurotransmitters, respectively. The heavy labeled MANTs standards were prepared and used as internal standards for quantification to minimize the matrix effects in mass spectrometry analysis. Low toxic bromobenzene (extractant) and acetonitrile (dispersant) were utilized in microextraction procedure. Under the optimized conditions, good linearity was observed with the limits of detection (S/N>3) and limits of quantification (S/N>10) in the range of 0.002-0.010 and 0.015-0.040nmol/L, respectively. Meanwhile, it also brought acceptable precision (4.2-8.8%, peak area RSDs %) and accuracy (recovery, 96.9-104.1%) results. This method was successfully applied to the simultaneous determination of monoamine neurotransmitters and their biosynthesis precursors and metabolites in rat brain microdialysates of Parkinson's disease and normal rats. This provided a new method for the neurotransmitters related studies in the future.

KEYWORDS:

In vivo microdialysis; Neurotransmitters; Sensitivity enhancement; Stable isotope-labeling derivatization; Targeted metabolomics; Triple quadrupole mass spectrometry

PMID:
28426993
DOI:
10.1016/j.jchromb.2017.03.039
[Indexed for MEDLINE]

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