期刊
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
卷 414, 期 6, 页码 2041-2054出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00216-021-03853-z
关键词
Sphingolipids; LC-MS/MS; Lipidomics; Plasma; Cardiometabolic diseases
资金
- National Natural Science Foundation of China [21190051, 91844000, 41421064]
Sphingolipids are a class of lipids with diverse structures and biological functions, and have been proposed as potential biomarkers for cardiometabolic diseases. The current methods for quantifying sphingolipids have limitations in terms of sample pretreatment and volume. In this study, a simple and rapid method using methanol for plasma sphingolipid extraction was developed, and 37 sphingolipids from 8 classes were successfully quantified using liquid chromatography coupled with tandem mass spectrometry. This method showed good performance and was applied successfully in an epidemiological study.
Sphingolipids are a class of lipids with high structural diversity and biological pleiotropy. Mounting evidence supports a role for sphingolipids in regulating pathophysiology of cardiometabolic diseases, and they have been proposed as potential cardiometabolic biomarkers. Current methods for quantifying sphingolipids require laborious pretreatment and relatively large sample volumes, and cover limited species, hindering their application in epidemiological studies. Herein, we applied a time-, labor-, and sample-saving protocol simply using methanol for plasma sphingolipid extraction. It was compared with classical liquid-liquid extraction methods and showed significant advantages in terms of simplicity, sphingolipid coverage, and sample volume. By coupling the protocol with liquid chromatography using a wide-span mobile phase polarity parameter and tandem mass spectrometry operated in dynamic multiple reaction monitoring mode, 37 sphingolipids from 8 classes (sphingoid base, sphingoid base phosphate, ceramide-1-phosphate, lactosylceramide, hexosylceramide, sphingomyelin, ceramide, and dihydroceramide) were quantified within 16 min, using only 10 mu L of human plasma. The current method showed good performance in terms of linearity (R-2 > 0.99), intra- and interbatch accuracy (70-123%) and precision (RSD < 12%), matrix effect (91-121%), recovery (96-101%), analyte chemical stability (deviation < 19%), and carryover (< 16%). We successfully applied this method to quantify 33 detectable sphingolipids from 579 plasma samples of an epidemiological study within 10 days. The quantified sphingolipid concentrations were comparable with previous studies. Positive associations of ceramide C22:0/C24:0 and their precursors with homeostasis model assessment of insulin resistance suggested that the synthesis of the ceramides might be involved in insulin resistance. This novel method constitutes a simple and rapid approach to quantify circulating sphingolipids for epidemiological studies using targeted lipidomic analysis, which will help elucidate the sphingolipid-regulated pathways underlying cardiometabolic diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据