Exploiting the formation of adducts in mobile phases with ammonium fluoride for the enhancement of annotation in liquid chromatography-high resolution mass spectrometry based lipidomics

Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) based lipidomics has become the most versatile analytical tool to discover and detect lipids using a non-targeted approach. A way to improve the ionization performance of specific lipid classes in electrospray sources is to modify their electrostatic interactions with both mobile and stationary phases. So far, studies on mobile phases additives, in particular ammonium fluoride, have focused on increasing ionization efficiency and reproducibility of the conditions. However, little attention has been paid to the different rules that apply in adducts formation: type of adducts, their relative intensities, and how this affects the annotation/identification process. In this study, we evaluated the performance of ammonium fluoride as an additive salt in a non-targeted MS-based lipidomic study under both the positive and negative electrospray ionization modes. The new molecular ion adducts observed can lead to wrong identifications if they are not known or considered, while the disappearance of other adducts such as those with sodium can change the traditional identification rules.