基于LC-MS的靶向脂质组学分析极大地推进了脂质组学的发展，但也面临灵敏度低、基质效应严重、缺乏标准品或同位素内标的问题。稳定同位素标记衍生化(SILD)技术是解决上述问题的有效办法之一，但现有SILD试剂种类较少，且难于合成，标记物LC-MS/MS分析性能有待提高。因此，设计、合成新型SILD试剂就成为该领域的关键科学问题之一。本项目拟采用廉价易得的6-喹啉-乙酸和罗丹明6G为原料，H/D卤代烷引入同位素标签，设计1-3步常规有机反应，制备轻/重、等重、iTRAQ-like三类SILD试剂，实现脂肪酸、羟基类固醇、磷脂酰丝氨酸、溶血磷脂酰丝氨酸的选择性标记，在此基础上建立LC-MS/MS分析方法，再结合生物信息学统计分析，以实现脂质标志物筛选、代谢通路构建、异构体结构解析、新代谢物发现、临床样本高通量检测等目的。本项目的实施可显著提高脂质组学信息挖掘的准确性和全面性，进而推动其快速发展。

LC-MS based targeted lipidomics analysis greatly promotes the development of lipidomics. But it also faces the underlying problems of low detection sensitivity, the serious matrix effect, and lack of standards or isotope internal standards. The technique of stable isotope labeling derivatization (SILD) is one of the effective ways to solve the above problems. However, the reported SILD reagents are less, and hard to be synthesized. And also the LC-MS/MS analytical performance of reported SILD derivatives needs to be improved. Therefore, the design and synthesis of novel SILD reagents have become one of the key scientific problems in this field. This project intends to use cheap and commercial available 6-quinoline-acetic acid and rhodamine 6G as raw materials, and H/D haloalkanes as the source of isotopic labels, to prepare three kinds of SILD reagents (light/heavy, isobaric and iTRAQ-like) by using 1-3 steps common organic synthesis reactions. It can be realized that fatty acid, hydroxyl steroids, phosphatidylserines and hemolysis phosphatidylserines can be selectively labeled. On this basis, LC-MS/MS analytical methods of those lipids above mentioned will be developed. Combined with statistical analysis of bioinformatics, the research objects of this project about lipid biomarkers screening, metabolic pathways construction, the structural analysis of lipid isomers, new lipid metabolites findings, and high throughput tests of clinical samples will be studied. The development of this project will remarkably improve the accuracy and comprehensiveness about information collection and searching of lipidomics, and this will accelerate its rapid development.