Recent Developments in Electron Ionization LC-MS with Cold EI

Svetlana Tsizin, Tel Aviv University, Tel Aviv, Israel (svet3@mail.tau.ac.il)
Tal Alon, Tel Aviv University, Tel Aviv, Israel
Alexander Fialkov, Tel Aviv University, Tel Aviv, Israel
Aviv Amirav, Tel Aviv University, Tel Aviv, Israel

A unique system of LC-MS that was developed in our group uses electron ionization (EI) on vibrationally cold molecules that are created by the generation of supersonic molecular beams (SMB). This EI-LC-MS-SMB system, unlike standard LC-MS instruments, that use atmospheric pressure ionization, enables automated library based identification and is free of any ion suppression effects that plague ESI and/or APCI. Moreover, ionization of cold molecules creates Cold EI spectra that are much more informative than standard EI. 

The EI-LC-MS-SMB instrument was combined with a Varian 1200 or Agilent 5977 MSD, both of which have quadrupole analyzer and a home-made fly-through ion source. The LC effluents are pneumatically sprayed inside a heated liner that is connected to the supersonic nozzle via a capillary flow restrictor to suppress cluster formation. Ones expended through this nozzle the sample compounds are vibrationally cooled prior to their ionization. The results of electron impact at this stage creates Cold EI mass spectrum that features a highly abundant molecular ion with extensive fragment information without any ion suppression or enhancement effects. Also, the use of the fly-through ion source eliminates any ion source degradation that is otherwise present. Overall this is the only LC-MS technique that enables library based identification of the compounds with their names and structures at the isomer level.

The many benefits of the system bridge over the gap between GC-MS and LC-MS worlds and show its superiority over a standard Electrospray LC-MS, for example, in analysis of small and non-polar molecules. The instrument was also used in analysis of cannabinoids in Cannabis flowers, anti-oxidants and polycyclic peptides. Recently we explored the size limit of our EI-LC-MS-SMB system and analyzed the cyclic 12 peptide Valinomycin C₅₄H₉₀N₆O₁₈ with molecular weight of 1110 which is a record size of polar compound in EI.