Recent Advances in the Mass Spectrometric Analysis of Glycosphingolipidome - A Review

Aberrant expression of glycosphingolipids has been implicated in a myriad of diseases, but our understanding of the strucural diversity, spatial distribution, and biological function of this class of biomolecules remains limited. These challenges partly stem from a lack of sensitive tools that can detect, identify, and quantify glycosphingolipids at the molecular level. Mass spectrometry has emerged as a powerful tool poised to address most of these challenges. Here, we review the recent developments in analytical glycosphingolipidomics with an emphasis on sample preparation, mass spectrometry and tandem mass spectrometry-based structural characterization, label-free and labeling-based quantification. We also discuss the nomenclature of glycosphingolipids, and emerging technologies like ion mobility spectrometry in differentiation of glycosphingolipid isomers. The intrinsic advantages and shortcomings of each method are carefully critiqued in line with an individual's research goals. Finally, future perspectives on analytical sphingolipidomics are stated, including a need for novel and more sensive methods in isomer separation, low abundance species detection, and profiling the spatial distribution of glycosphingolipid molecular species in cells and tissues using imaging mass spectrometry.