Shotgun lipidomics: Electrospray ionization mass spectrometric analysis and quantitation of cellular lipidomes directly from crude extracts of biological samples

Abstract Lipidomics, after genomics and proteomics, is a newly and rapidly expanding research field that studies cellular lipidomes and the organizational hierarchy of lipid and protein constituents mediating life processes. Lipidomics is greatly facilitated by recent advances in, and novel applications of, electrospray ionization mass spectrometry (ESI/MS). In this review, we will focus on the advances in ESI/MS, which have facilitated the development of shotgun lipidomics and the utility of intrasource separation as an enabling strategy for utilization of 2D mass spectrometry in shotgun lipidomics of biological samples. The principles and experimental details of the intrasource separation approach will be extensively discussed. Other ESI/MS approaches towards the quantitative analyses of global cellular lipidomes directly from crude lipid extracts of biological samples will also be reviewed and compared. Multiple examples of lipidomic analyses from crude lipid extracts employing these approaches will be given to show the power of ESI/MS techniques in lipidomics. Currently, modern society is plagued by the sequelae of lipid‐related diseases. It is our hope that the integration of these advances in multiple disciplines will catalyze the development of lipidomics, and such development will lead to improvements in diagnostics and therapeutics, which will ultimately result in the extended longevity and an improved quality of life for humankind. © 2004 Wiley Periodicals, Inc., Mass Spec Rev 24:367–412, 2005