An extendable all-in-one injection twin derivatization LC-MS/MS strategy for the absolute quantification of multiple chemical-group-based submetabolomes
An extendable all-in-one injection twin derivatization LC-MS/MS strategy for the absolute quantification of multiple chemical-group-based submetabolomes
复制标题
一种可扩展的一体式注射双衍生 LC-MS/MS 策略，用于对多个基于化学基团的亚代谢组进行绝对定量
DOI：
10.1016/j.aca.2019.02.001
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发表时间：
2019-07-31
影响因子：
6.2
通讯作者：
Xu, Fengguo
中科院分区：
文献类型：
--
作者：
Huang, Yezhen;Jiao, Yu;Xu, Fengguo
LC-MS/MS用于高覆盖代谢物分析的能力落后于全球代谢组学的要求。化学衍生化的引入可以显著扩展LCMS/MS的能力，增强MS响应和改善LC分离，其已成为代谢组学分析的有前途的定量工具。然而，由于一种特异性衍生试剂通常靶向某个部分，因此在一次进样中只能分析单个基于化学基团的亚代谢物组。因此，基于衍生化的LC-MS/MS检测代谢物的覆盖范围很大程度上受到限制。为了克服基于衍生化的LC-MS的这一技术障碍并增加亚代谢组覆盖率，我们提出了可扩展的一体化注射LC-MS/MS策略。以5-二甲氨基萘磺酰氯（Dns-Cl）/5-二乙氨基萘磺酰氯（Dens-Cl）和5-二甲氨基萘磺酰哌嗪（Dns-PP）/5-二乙氨基萘磺酰哌嗪（Dens-PP）为双标记试剂，分别标记氨基/酚和羧基亚代谢物组。提出了“串联模式”和“并联模式”，并使用8种代表性标准品进行了研究，同时考虑了不同衍生化系统之间的相互作用、时间消耗和可扩展性。结果发现，“串联模式”导致产率降低，而“并联模式”得到的结果与单独衍生化的结果相同。最后，选择“平行模式”来开发可扩展的所有在一个注射双衍生化LC-MS/MS策略，以定量分配到5类微生物代谢物的80种代谢物，包括多胺，氨基酸，吲哚衍生物，胆汁酸和游离脂肪酸。与伊立替康（CPT-11）诱导胃肠道毒性模型的大鼠血清中的非靶向方法相比，该经过充分验证的方法绝对定量了67种代谢物，并发现了额外的40种差异代谢物。(C)2019由Elsevier B. V.出版
The ability of LC-MS/MS for high coverage metabolite analysis lags behind the requirements of global metabolomics. The introduction of chemical derivatizations could significantly extend the ability of LCMS/MS with enhanced MS response and improved LC separation, which has been serving as a promising quantitative tool for metabolomic analysis. However, as one specific derivatization reagent usually targets to a certain moiety, only a single chemical-group-based submetabolome could be analyzed in one injection. Therefore, the coverage of detected metabolites by derivatization-based LC-MS/MS is largely limited. To overcome this technical obstacle of derivatization-based LC-MS and increase submetabolome coverage, we proposed an extendable all-in-one injection LC-MS/MS strategy. 5-dimethylamino-naphthalene-1-sulfonyl chloride (Dns-Cl)/5-diethylamino-naphthalene-1-sulfonyl chloride (Dens-Cl) and 5-dimethylamino-naphthalene-1-sulfonyl piperazine (Dns-PP)/5-diethylamino-naphthalene-1-sulfonyl piperazine (Dens-PP) were used as twins labeling reagents for amino/phenol and carboxyl submetabolomes, respectively. "Series Mode" and "Parallel Mode" were proposed and investigated using eight representative standards with the consideration of interaction between different derivatization systems, time-consumption, and extendability. As a result, we found that "Series Mode" led to yield reduction, while "Parallel Mode" gave identical results with those of individual derivatization. Finally, a "Parallel Mode" was chosen to develop an extendable all-in-one injection twin derivatization LC-MS/MS strategy to quantify eighty metabolites assigned to five classes of microbial metabolites, including polyamines, amino acids, indole derivatives, bile acids, and free fatty acids. This well-validated method quantified 67 metabolites absolutely and discovered additional 40 differential metabolites compared with the untargeted method in rat serum from irinotecan (CPT-11)-induced gastrointestinal toxicity model. (C) 2019 Published by Elsevier B.V.