A systematic approach to development of analytical scale and microflow-based liquid chromatography coupled to mass spectrometry metabolomics methods to support drug discovery and development.
A systematic approach to development of analytical scale and microflow-based liquid chromatography coupled to mass spectrometry metabolomics methods to support drug discovery and development.
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DOI:
10.1016/j.chroma.2021.462047
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发表时间:
2021-04-12
期刊:
影响因子:
--
通讯作者:
Ivanov AR
中科院分区:
文献类型:
--
作者:
Geller S;Lieberman H;Kloss A;Ivanov AR
As the reliance on metabolic biomarkers within drug discovery and development increases, there is also an increased demand for global metabolomics methods to provide broad metabolome coverage and sensitivity towards differences in metabolite expression and reproducibility. A systematic approach is necessary for the development, and evaluation, of metabolomics methods using either conventional techniques or when establishing new methods that allow for additional gains in sensitivity and a reduction in requirements for amounts of a biological sample, such as those seen with methods based on microseparations. We developed a novel standard mixture and used a systematic approach for the development and optimization of optimal, ion-pair free, liquid chromatography-mass spectrometry (LC-MS) global profiling methods. These methods were scaled-down to microflow-based LC separations and compared with analytical flow ion-pairing reagent containing methods. Average peak volume improvements of 7- and 22-fold were observed in the positive and negative ionization mode microflow methods as compared to the ion-pairing reagent analytical flow methods, respectively. The linear range of the newly developed microflow methods showed up to a 10-fold increase in the lower limit of detection in the negative ionization mode. The developed microflow LC-MS methods were further evaluated using wild-type mouse plasma where up to a 9-fold increase in peak volume was observed.
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影响因子:
6.1
作者:
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通讯作者:
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影响因子:
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作者:
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DOI:
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发表时间:
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影响因子:
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通讯作者:
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DOI:
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发表时间:
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期刊:
METABOLIC PROFILING: METHODS AND PROTOCOLS
影响因子:
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作者:
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通讯作者:
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