Continuous‐flow extractive desorption electrospray ionization coupled to normal phase separations and for direct lipid analysis from cell extracts

Normal phase liquid chromatography is a common mode for chiral separations. Many chiral amines are used as drugs or are important intermediates for drug synthesis. Electrospray ionization mass spectrometry is well known for its high sensitivity. However, when using normal phase liquid chromatography, electrospray ionization is hampered by the poor ionization efficiency of analytes from organic eluents. Continuous-flow extractive desorption electrospray ionization, which introduces the eluents through a hypodermic needle into the electrospray plume is demonstrated here for its success to interface normal phase liquid chromatography to mass spectrometry detection. Such an approach was shown to be as or more sensitive than ultraviolet detection for a selected set of aromatic amine-functionalized enantiomers. Also demonstrated is the direct infusion of cell extracts to monitor phospholipids from three different bacterial cells. Despite their presence in non-electrospray-ionization-friendly extraction solvents, continuous-flow extractive desorption electrospray ionization enabled the sensitive detection of phospholipids and the ability to tune ion forms through incorporation of different spray modifiers.