Electrospray ionization mass spectrometry lipid analysis

Cai SS, Syage JA. Comparison of atmospheric pressure photoionization, atmospheric pressure chemical ionization, and electrospray ionization mass spectrometry for analysis of lipids. Anal. Chem. 2006 78 1191-1199. 

Electrospray mass spectrometry has developed into a well-established method of wide scope and potential over the past 15 years. The softness of electrospray ionization has made this technique an indispensable tool for biochemical and biomedical research. Electrospray ionization has revolutionized the analysis of labile biopolymers, with applications ranging from the analysis of DNA, RNA, oligonucleotides, proteins as well as glycoproteins to carbohydrates, lipids, gly-colipids, and lipopolysaccharides, often in combination with state-of-the-art separation techniques like liquid chromatography or capillary electrophoresis [1,2]. Beyond mere analytical applications, electrospray ionization mass spectrometry (ESMS) has proven to be a powerful tool for collision-induced dissociation (CID) and multiple-stage mass spectrometric (MSn) analysis, and - beyond the elucidation of primary structures - even for the study of noncovalent macromolecular complexes [3]. 

Analytical methods for tocol analysis have continued to improve, as noted by Abidi (2000), and in the intervening ten years, as noted in this chapter. We predict that advances will continue to be made in the field of the chromatographic analysis of tocols. Also, we believe that lipidomic methods (quantitative analysis via direct injection tandem electrospray ionization mass spectrometry) will be developed for the rapid analysis of tocols, just as these methods have already been used for the profiling of phospholipids and glycolipids (Han, 2011 Welti, 2011). These methods usually involve the direct injection of lipid samples into a... 

Figure 2.10 Reconstructed MRM traces for Bligh/Dyer extract of sterols from mouse brain. Known sterols are labeled, unknown compounds with a sterollike signature are indicated by . MS/MS of the respective steroids can be found at Lipid Maps http //www.lipidmaps.org/data/standards/standards. php lipidclass=LMST. (Reproduced with permission from McDonald, J. G. et al., 2007, Extraction and Analysis of Sterols in Biological Matrices by High-Performance Liquid Chromatography Electrospray Ionization Mass Spectrometry, Methods Enzymol. 432 145-70.)...

Paglia, G Ifa, D.R., Wu, C Corso, G., Cooks, R.G. (2010) Desorption Electrospray Ionization Mass Spectrometry Analysis of Lipids after Two-dimensional High-Performance Thin-Layer Chromatography Partial Separation. Anal. Chem. 82 ... 

Schrick, K., Shiva, S., Arpin, J.C., Delimont, N., Isaac, G., Tamura, P. and Welti, R. (2012) Steryl glucoside and acyl steryl glucoside analysis of Arabidopsis seeds by electrospray ionization tandem mass spectrometry. Lipids 47,185-193. 

Although several technologies have been used in lipidomics to identify, quantify, and understand the structure and function of lipids in biological systems, it is clear that the progress of lipidomics has been accelerated by the development of modern mass spectrometry (e.g., electrospray ionization (ESI) and matrix-assisted laser desorption/ionization). Mass spectrometric analysis of lipids plays a key role in the discipline. Therefore, this book is focused on the mass spectrometry of lipids that has occurred in these years. Other technologies for analysis of lipids, particularly those with chromatography, can be found in the book entitled Lipid Analysis Isolation, Separation, Identification and Lipidomic Analysis written by Drs William W. Christie and Xianlin Han. Readers who are interested in classical techniques and applications of mass spectrometry for analysis of lipids should refer to Dr Robert C. Murphy s book entitled Mass Spectrometry of Lipids. 

Schneiter, R. Brugger, B. Sandhoff, R. Zellnig, G. Leber, A. Lampl, M. Athenstaedt, K. Hrastnik, C. Eder, S. Daum, G. Paltauf, F. Wieland, F. T. Kohlwein, S. D. Electrospray ionization tandem mass spectrometry (ESI-MS/MS) analysis of the lipid molecular species composition of yeast subcellular membranes reveals acyl chain-based sorting/remodeling of distinct molecular species en route to the plasma membrane. J. Cell Biol. 1999,146,741-754. 

D1 (10,17S-docosatriene) from DHA using tandem liquid chromatography-photodiode array-electrospray ionization-tandem mass spectrometry (LC-PDA-ESI-MS-MS)-based lipidomic analysis have been documented in ischemic brain [4] and retinal pigment epithelium [5], This new lipid is called neuroprotectin D1 (1) because of its neuro-protectiveproperties in brain ischemia-reperfusion [4] and in oxidative stress-challenged retinal pigment epithelial cells [5] (2) because of its potent ability to inactivate proapoptotic signaling (see apoptosis, Ch. 35) [5] and (3) because it is the first identified neuroprotective mediator derived from DHA. 

A newer approach for lipid analysis is electrospray ionization tandem mass spectrometry (ESI-MS/MS) (Welti et al., 2002). This method requires limited sample preparation and sample size to identify and quantify lipids. Fauconnier et al. (2003) used ESI-MS/MS to analyze phospholipid and galactolipid levels during aging of potato tubers. 

Advanced analytical techniques, particularly mass spectrometry (MS), often combined with liquid chromatography (LC) or gas chromatography (GC), are requisite for lipid analysis and they have played the crucial role in the emergence as well as the progresses of lipidomics. MS is the principal choice for the lipid analysis, particularly using electrospray ionization (ESI) and sometimes also atmospheric pressure chemical ionization or laser-based MS methods for surface analysis. The MS-based techniques are the best choice for lipidomics due to their superior sensitivity and molecular specificity, and because they provide the ability to resolve the extensive compositional and structural diversity of lipids in biological systems. 

In recent years the rapid development of high-sensitivity analytical techniques such as mass spectrometry (MS) and liquid chromatography (LC) supported the investigation of the endocannabinoids as part of a complex lipid network. The identification of lipid components of the endocannabinoid system can be achieved in a single analytical step by state-of-the-art platforms such as tandem mass spectrometry (MS/MS), which provides the detailed structural information necessary for characterization of lipids and increases specificity in complex biological matrices. Furthermore, the implementation of ionization techniques such as electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) allow the coupling of LC to MS, and permits the separation and analysis of endocannabinoids with greater speed and accuracy. 

The dynamic development of mass spectrometry has had a huge impact on lipid analysis. Currently, a variety of suitable mass spectrometers is available. In principal, a mass spectrometer consists of an ion source, a mass analyzer, and an ion detector. The typical features of each instrument (Fig. 2) result mostly from the types of ion source and mass analyzer. To date, the ionization techniques apphed to lipid analysis include Electrospray Ionization (ESI or nano-ESI), Atmospheric Pressure Chemical Ionization (APCI), Matrix-Assisted Laser Desorption/Ionization... 

Brtigger B, Erben G, Sandhoff R, Wieland FT, Lehmann WD. Quantitative analysis of biological membrane lipids at the low picomole level by nano electrospray ionization tandem mass spectrometry. Proc. Natl. Acad. Sci. U.S.A. 1997 94 2339-2344. 

Nearly all known ionization methods of mass spectrometry (including electron impact, laser desorption and fast atom bombardment) were already successfully applied to lipids. However, many ionization techniques are not very suitable for the analysis of complex PL mixtures as they provide considerable amounts of fragment ions. Therefore, only three soft-ionization methods play nowadays a major role in lipid analysis. Beside atmospheric pressure chemical ionization (APCI) (Byrdwell 2001), electrospray ionization (ESI) (Pulfer and Murphy... 

Figure 9.2 The basic components of a mass spectrometer. All mass spectrometers consist of an ion source linked to a mass analyser then to a detector. The important ion sources and mass analysers for biological mass spectrometry are listed. There are many other potential ion sources and mass analysers used generally in mass spectrometry, but only the indicated are of use in the analysis of biological macromolecules and amphiphilic lipids, and also in proteomics FAB fast atom bombardment MALDI matrix-assisted laser desorption and ionization ESI electrospray ionization ToF time of flight FTICR fourier transform ion cyclotron resonance MS/MS tandem mass spectrometry.

One of the most powerful techniques used in Upid analysis today is HPLC coupled with mass spectrometry (HPLC/MS). Several mass spectrometric ionization techniques, such as fast atom bombardment (FAB) [23], electrospray ionization (ESI) [29,30], ionspray ionization (ISI) [31], and atmospheric pressure chemical ionization (APCI) [22,30,32] have been used. By using HPLC/MS, one can get information on the molecular structure of the intact lipids, which helps differentiate molecular species within different lipid classes. By using tandem mass spectrometry (MS/MS), identification of molecular species of different sphingolipids can be achieved in an easier and more sensitive way. There are many other advantages of using MS, such as small sample size, minimal sample preparation, and lack of need for derivatization, speeds, and sensitivity. In the literature, sphingolipids of both animal and plant origin were analyzed by MS. 

The separation of intact polar lipids by liquid chromatography (LC) and the subsequent detection by mass spectrometry (MS) has today become straightforward. LC-MS is no longer a sophisticated technique only in the hands of specialists. Today, it is a routinely used, although advanced, analytical technique. The fields of application are expanding and today the use of LC-MS with electrospray (ES) ionization grows at the expense of other ionization techniques, at least where analysis of intact polar lipids is concerned. 

The content of this chapter focuses on the analysis of intact polar lipids by high-pressure liquid chromatography (HPLC) with flow or loop injection -and mass spectrometry (MS) or tandem mass spectrometry (MS-MS) using thermospray (TS), discharge-assisted TS [or plasmaspray (PSP)], electrospray (ES) and atmospheric pressure chemical ionization (APCI). It was intended to include only those papers describing the analysis of intact polar lipids by liquid chromatography on-line with MS. However, many papers describe flow or loop injection with MS and/or the analysis of derivatives of polar lipids. These papers, describing excellent applications of MS and/or MS-MS of polar lipids, are included since this chapter would not have been complete without them. 

Han, X., Gross, R.W (2001) Quantitative analysis and molecular species fingerprinting of triacylglyceride molecular species directly from lipid extracts of biological samples by electrospray ionization tandem mass spectrometry. Analytical Biochemistry, 295, 88-100. 

Hsu, E.-E. and Turk, J. (2005) Electrospray ionization with low-energy collisionally activated dissociation tandem mass spectrometry of complex lipids Structural characterization and mechaiusm of fragmentation. In Modern Methods for Lipid Analysis by Liquid Chromatography/Mass Spectrometry and Related Techiuques (Byrdwell, W.C., ed.). pp. 61-178, AOCS Press, Champaign, IL. 

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