Serum lipidomics profiling using LC-MS and high-energy collisional dissociation fragmentation: focus on triglyceride detection and characterization.
Serum lipidomics profiling using LC-MS and high-energy collisional dissociation fragmentation: focus on triglyceride detection and characterization.
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DOI：
10.1021/ac201195d
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发表时间：
2011-09-01
影响因子：
7.4
通讯作者：
Kristal, Bruce S.
中科院分区：
文献类型：
--
作者：
Bird, Susan S.;Marur, Vasant R.;Sniatynski, Matthew J.;Greenberg, Heather K.;Kristal, Bruce S.
在临床和实验上都有越来越多的需要来改善血脂的表征。液相色谱-质谱（LC-MS）法，开发用于定性和半定量检测生物样品中的脂质和以前在线粒体样品中验证，现在评价了血清脂质的分析。使用高分辨率全扫描MS和高能碰撞解离（HCD）全离子碎裂获得数据。该方法设计用于在正离子和负离子模式下进行有效分离和检测，并使用跨越7种脂质类别的标准品进行评价。使用提取离子色谱图评估与血清甘油三酯（TG）鉴别和表征相关的平台性能，质量容差窗口为5 ppm或更低，来自使用SIEVE非差示LC-MS分析软件测定的全扫描精确质量测量值。该平台显示保留时间变异系数（CV）<0.3%，质量准确度值< 2 ppm误差和峰面积CV <13%，其中大部分误差来自样品制备和提取，而不是LC-MS分析，并且对于掺入血清中的标准TG（15：0）3，线性显示超过四个数量级（r2=0.999）。仪器质量准确度和精密度对于鉴定未知TG物质至关重要，部分原因是这些参数使我们能够减少假阳性。除了血清中TG的检测和相对定量外，还通过使用不同能量的交替HCD扫描来表征TG结构，以在分析中对所有离子产生诊断碎片。脂质组学方法应用于192只大鼠的血清样品，这些大鼠维持在不同的常量营养素组成的饮食中。该分析确定了86种TG物种，具有81种独特的质量，变化超过3.5个数量级，并显示出饮食依赖性-与TG联系饮食和疾病风险一致。
There is a growing need both clinically and experimentally to improve the characterization of blood lipids. A liquid chromatography-mass spectrometry (LC-MS) method, developed for the qualitative and semi-quantitative detection of lipids in biological samples and previously validated in mitochondrial samples, was now evaluated for the profiling of serum lipids. Data were acquired using high resolution full scan MS and high energy collisional dissociation (HCD) all ion fragmentation. The method was designed for efficient separation and detection in both positive and negative ionization mode and evaluated using standards spanning 7 lipid classes. Platform performance, related to the identification and characterization of serum triglycerides (TGs) was assessed using extracted ion chromatograms with mass tolerance windows of 5 ppm or less from full scan exact mass measurements determined using SIEVE non-differential LC-MS analysis software. The platform showed retention time coefficients of variation (CV) < 0.3%, mass accuracy values < 2 ppm error and peak area CV < 13%, with the majority of that error coming from sample preparation and extraction rather than the LC-MS analysis and linearity was shown to be over four orders of magnitude (r2=0.999) for the standard TG (15:0)3 spiked into serum. Instrument mass accuracy and precision were critical to the identification of unknown TG species, in part because these parameters enabled us to reduce false positives. In addition to detection and relative quantitation of TGs in serum, TG structures were characterized through the use of alternating HCD scans at different energies to produce diagnostic fragmentations on all ions in the analysis. The lipidomics method was applied to serum samples from 192 rats maintained on diets differing in macronutrient composition. The analysis identified 86 TG species with 81 unique masses that varied over 3.5 orders of magnitude and showed diet-dependency - consistent with TGs linking diet and disease risk.
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影响因子：
14.9
作者：
Wishart DS;Knox C;Guo AC;Eisner R;Young N;Gautam B;Hau DD;Psychogios N;Dong E;Bouatra S;Mandal R;Sinelnikov I;Xia J;Jia L;Cruz JA;Lim E;Sobsey CA;Shrivastava S;Huang P;Liu P;Fang L;Peng J;Fradette R;Cheng D;Tzur D;Clements M;Lewis A;De Souza A;Zuniga A;Dawe M;Xiong Y;Clive D;Greiner R;Nazyrova A;Shaykhutdinov R;Li L;Vogel HJ;Forsythe I
通讯作者：
Forsythe I
影响因子：
2.9
作者：
Han, XL;Yang, JY;Gross, RW
通讯作者：
Gross, RW
影响因子：
8.2
作者：
Corpeleijn, E.;Feskens, E. J. M.;Blaak, E. E.
通讯作者：
Blaak, E. E.
影响因子：
4.4
作者：
Hu, Chunxiu;van Dommelen, Judith;Hankemeier, Thomas
通讯作者：
Hankemeier, Thomas
影响因子：
2.3
作者：
Ejsing, CS;Moehring, T;Shevchenko, A
通讯作者：
Shevchenko, A