Drug-mediated ion suppression and mitigation of interferences using liquid chromatography-quadrupole/time of flight mass spectrometry (LC-Q/TOF-MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS)

J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Sep 1;1152:122265. doi: 10.1016/j.jchromb.2020.122265. Epub 2020 Jul 14.


Liquid-chromatography mass spectrometry (LC-MS) is a powerful bioanalytical tool that is gaining widespread use in operational forensic toxicology laboratories. However, changes in ionization efficiency caused by endogenous or exogenous species must be carefully considered. While different modes of ionization can be used, electrospray ionization (ESI) can be especially prone to this phenomenon due to capacity-limited ionization. This decreased ionization efficiency can influence the accuracy and sensitivity of analytical methods. While quantitative matrix effects are evaluated routinely during method development and validation, drug-mediated ion suppression is not always assessed quantitatively, or in sufficient depth. Although stable isotope labeled internal standards (SIL-IS) can mitigate this issue, they are not always commercially available, particularly for new or emerging substances. In this study, the hypnotic drug suvorexant was used as a model compound for the investigation of such interferences. The potential for significant bias in quantitative analysis was demonstrated using this previously validated assay. In this study, quantitative biases due to ionization suppression are discussed, and techniques to overcome this challenge are presented. Decreases in specimen and injection volume were shown to significantly reduce quantitative bias due to drug-mediated suppression. This straight-forward approach can improve the robustness of analytical methodology, which is particularly important when quantitative measurements are relied upon for medicolegal and other purposes.

Keywords: Forensic toxicology; Interferences; Ion suppression; LC-MS/MS; LC-Q/TOF-MS; Suvorexant.

MeSH terms

  • Azepines
  • Chromatography, Liquid / methods*
  • Forensic Toxicology / methods
  • Forensic Toxicology / standards
  • Ions* / analysis
  • Ions* / chemistry
  • Models, Chemical
  • Pharmaceutical Preparations* / analysis
  • Pharmaceutical Preparations* / chemistry
  • Reference Standards
  • Reproducibility of Results
  • Spectrometry, Mass, Electrospray Ionization / methods
  • Tandem Mass Spectrometry / methods*
  • Triazoles


  • Azepines
  • Ions
  • Pharmaceutical Preparations
  • Triazoles
  • suvorexant