Isotope Corrected Chiral and Achiral Nontargeted Metabolomics: An Approach for High Accuracy and Precision Metabolomics Based on Derivatization and Its Application to Cerebrospinal Fluid of Patients with Alzheimer's Disease.
Isotope Corrected Chiral and Achiral Nontargeted Metabolomics: An Approach for High Accuracy and Precision Metabolomics Based on Derivatization and Its Application to Cerebrospinal Fluid of Patients with Alzheimer's Disease.
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DOI：
10.1021/acs.analchem.8b04852
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发表时间：
2019-03
影响因子：
7.4
通讯作者：
Takahiro Takayama;H. Mizuno;T. Toyo′oka;H. Akatsu;K. Inoue;K. Todoroki
中科院分区：
文献类型：
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作者：
Takahiro Takayama;H. Mizuno;T. Toyo′oka;H. Akatsu;K. Inoue;K. Todoroki
我们提出了一种基于数据依赖的 MS/MS 分析 (DDA) 的手性代谢组学方法，使用高分辨率四极杆飞行时间质谱 (Q-TOFMS) 和 13C 同位素编码衍生化 (ICD) 试剂，即 iDMT-( S)-A 和 iDMT-( S)-PO。该方法的优点是通过同位素编码和非编码试剂的平行衍生化来校正所有检测到的衍生物。还开发了使用 MSDIAL 和 ICD 判别程序的自动数据分析平台（称为 DINA）并用于数据分析过程。结果，在自动数据分析步骤中正确识别了异构体的0.5-2.0%（d-/l-异构体）变化。由于 DDA 分析得出的 MS 和 MS/MS 谱图的高分辨率/准确性，半定量比较和鉴定效率均得到提高。该方法用于阿尔茨海默病 (AD) 患者脑脊液 (CSF) 中生物标志物的发现。成功确定了 24 个候选生物标志物，其中包括 8 个手性生物标志物。
We propose a chiral metabolomics approach based on a data-dependent MS/MS analysis (DDA) using high-resolution quadrupole-time-of-flight mass spectrometry (Q-TOFMS) and 13C-isotope coded derivatization (ICD) reagents, i.e., iDMT-( S)-A and iDMT-( S)-PO. The advantage of the method is the correction of all detected derivatives by parallel derivatization of the isotope-coded and noncoded reagents. The automatic data analysis platform using an MSDIAL and ICD discrimination program, called DINA, was also developed and used for the data analysis process. As a result, a 0.5-2.0% (d-/l-isomer) variation of the isomers was correctly recognized in the automatic data analysis step. Both the semiquantitative comparison and identification efficiency were improved as a result of the high resolution/accuracy of the MS and MS/MS spectra derived from the DDA analysis. This method was used for biomarker discovery in the cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD). Twenty-four biomarker candidates were successfully determined, including 8 chiral ones.