Challenges in Mass Spectrometry-based Lipidomics of Neutral Lipids

Mass spectrometry has played a critical role in the identification and quantitation of neutral lipids such as cholesteryl esters and triacylglycerols present in biological extracts. Various strategies have emerged in order to carry out such lipidomics studies since a large number of neutral lipid molecular species exist in tissues. These include both shotgun approaches as well as those engaging liquid chromatographic separation of species prior to mass spectrometric analysis. Nonetheless challenges remain at every level of the lipidomics experiment, including extraction of lipids, identification of specific species, and quantitation of the vast array of lipids present in the sample extract. Unambiguous identification of molecular species present (qualitative analysis) as well as precise quantitation remains as significant challenges. The relative quantitation enables quite accurate assessment of fold changes of complex lipid species without exact quantitation. The availability of reference standard material as well as relevant internal standards continue to be limited.