Innovative Approaches to LC-MS: The Role of Electron and Chemical Ionization.

Liquid electron ionization (LEI) interface is a device that converts a liquid phase to a gas phase in an mass spectrometer (MS) equipped with an electron ionization (EI) source. Analytes in the liquid phase vaporize at atmospheric pressure inside a specific vaporization microchannel (VMC) before entering the ion source where they are ionized under the EI conditions generating library searchable spectra with strong matrix effects mitigation, even in complex samples. In this study, the first goal was to explore the versatility of LEI in direct analysis (without chromatographic separations) using EI and CI with low and high-resolution mass spectrometry. The second goal was to assess the possibility of coupling normal phase liquid chromatography (NPLC) with electron ionization in low and high-resolution mass spectrometry using LEI. LEI performances in direct analysis were evaluated by developing a sustainable and rapid method for the analysis of complex biological and environmental samples . The system is composed of a microfluidic open interface (MOI) for solid-phase microextraction (SPME) liquid phase desorption, connected to LEI. A triple-quadrupole-tandem MS (QQQ, low-resolution) and a quadrupole-time-of-flight MS (QTOF, high-resolution), operating in EI and negative chemical ionization (NCI) conditions were used. Fentanyl and two halogenated pesticides (dicamba and tefluthrin) were chosen as model compounds and extracted respectively from human blood serum and from a commercial formulation matrix (CF) using a C18 fiber by direct immersion. Analytes desorption occurs in static conditions inside MOI filled with acetonitrile (ACN). Extraction and desorption steps were optimized to increase efficiency and accelerate the process. The system demonstrated good linearity, repeatability, and LODs and LOQs in the μg/L range for fentanyl in serum and in pg/mL range for dicamba and tefluthrin in CF. A new analytical approach based on the coupling of NPLC with electron ionization in low and high-resolution mass spectrometry by the use of LEI is presented. The advantages of NPLC, such as the fast separation of non-polar compounds and the possibility of isomers separation, are successfully combined with the generation of EI spectra and the HRMS identification power for the analysis of complex matrices. NPLC was coupled to a QQQ-MS and to a QTOF-MS equipped with the LEI interface. Tocopherols, cannabinoids, phenols, and phthalates were used as model compounds, and the separations were performed using a silica column with NPLC typical solvents in isocratic mode. VMC temperature and composition of the mobile phases have been optimized for each class of compound. Another goal of this study was to develop a new dispositive called E-LEI-MS that allows the coupling of ambient sampling with EI providing identification based on the comparison with NIST library for the analysis in pharmaceuticals, forensic and artwork fields and in pesticide analysis and food quality control.