• LC–MS;
  • nano-HPLC;
  • electron ionization;
  • Direct-EI interface;
  • matrix effects


This review article will give an up-to-date and exhaustive overview on the efficient use of electron ionization (EI) to couple liquid chromatography and mass spectrometry (LC–MS) with an innovative interface called Direct-EI. EI is based on the gas-phase ionization of the analytes, and it is suitable for many applications in a wide range of LC-amenable compounds. In addition, thanks to its operating principles, it prevents unwelcome matrix effects (ME). In fact, although atmospheric pressure ionization (API) methodologies have boosted the use of LC–MS, the related analytical methods are sometime affected by inaccurate quantitative results, due to unavoidable and unpredictable ME. In addition, API's soft ionization spectra always demand for costly and complex tandem mass spectrometry (MS/MS) instruments, which are essential to acquire an “information-rich” spectrum and to obtain accurate quantitative information. In EI a one-stage analyzer is sufficient for a qualitative investigation and MS/MS detection is only used to improve sensitivity and to cut chemical noise. The technology illustrated here provides a robust and straightforward access to classical, well-characterized EI data for a variety of LC applications, and readily interpretable spectra for a wide range of areas of research. The Direct-EI interface can represent the basis for a forthcoming universal LC–MS detector for small molecules. © 2010 Wiley Periodicals, Inc., Mass Spec Rev 30:1242–1255, 2011