Comparison of electrospray LC–MS, LC–MS with Cold EI and GC–MS with Cold EI for sample identification

Abstract

Electrospray LC–MS, LC–MS with Cold EI and GC–MS with Cold EI (Electron Ionization (EI) of vibrationally cold molecules in supersonic molecular beams (SMB)) are compared in their sample identification capabilities. Two test mixtures were used: (a) acetaminophen, caffeine, sulfadimethoxine, terfenadine and reserpine; and (b) octafluoronaphthalene (OFN), pyrene, cholesterol and agidol 40. The major strength of EI in both LC–MS with Cold EI and GC–MS with Cold EI is its compatibility with library based sample identification that provides samples names and structures at the isomer level. GC–MS with Cold EI alleviates two major downsides of GC–MS with standard EI as it provides enhanced molecular ions that are often weak or missing in standard EI and, it significantly extends the range of compounds that are amenable for analysis. Consequently, reserpine and agidol 40 that are incompatible with standard GC–MS analyses are analyzed by GC–MS with Cold EI and yield effective library based identification. In cases involving sample compounds that are not in the library, ESI–LC–MS provides elemental formula information (when combined with high resolution MS) while GC–MS with Cold EI also provides elemental formula when TAMI software is used for the quadrupole mass accuracy improvement combined with isotope abundance analysis. We found that both LC–MS with Cold EI and GC–MS with Cold EI have broader range of small molecules amenable for analysis than ESI–LC–MS that fails to analyze relatively non-polar compounds and exhibits highly non-uniform and compound dependent ionization yields that span over four orders of magnitude. The total ion mass chromatograms S/N of ESI–LC–MS and LC–MS with Cold EI are comparable while it is better (>100 times per on-column amount) for GC–MS with Cold EI.