Rapid Screening of Acetylcholinesterase Inhibitors by Effect-Directed Analysis Using LC × LC Fractionation, a High Throughput in Vitro Assay, and Parallel Identification by Time of Flight Mass Spectrometry.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: American Chemical Society Country of Publication: United States NLM ID: 0370536 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-6882 (Electronic) Linking ISSN: 00032700 NLM ISO Abbreviation: Anal Chem Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, American Chemical Society.
    • Subject Terms:
      Acetylcholinesterase/*metabolism ; Cholinesterase Inhibitors/*analysis ; Cholinesterase Inhibitors/*chemistry ; High-Throughput Screening Assays/*methods ; Mass Spectrometry/*methods; Cholinesterase Inhibitors/pharmacology ; Chromatography, High Pressure Liquid/instrumentation ; High-Throughput Screening Assays/instrumentation ; Humans ; Mass Spectrometry/instrumentation ; Time Factors
    • Abstract:
      Effect-directed analysis (EDA) is a useful tool to identify bioactive compounds in complex samples. However, identification in EDA is usually challenging, mainly due to limited separation power of the liquid chromatography based fractionation. In this study, comprehensive two-dimensional liquid chromatography (LC × LC) based microfractionation combined with parallel high resolution time of flight (HR-ToF) mass spectrometric detection and a high throughput acetylcholinesterase (AChE) assay was developed. The LC × LC fractionation method was validated using analytical standards and a C18 and pentafluorophenyl (PFP) stationary phase combination was selected for the two-dimensional separation and fractionation in four 96-well plates. The method was successfully applied to identify AChE inhibitors in a wastewater treatment plant (WWTP) effluent. Good orthogonality (>0.9) separation was achieved and three AChE inhibitors (tiapride, amisulpride, and lamotrigine), used as antipsychotic medicines, were identified and confirmed by two-dimensional retention alignment as well as their AChE inhibition activity.
    • Accession Number:
      0 (Cholinesterase Inhibitors)
      EC 3.1.1.7 (Acetylcholinesterase)
    • Publication Date:
      Date Created: 20160113 Date Completed: 20161024 Latest Revision: 20161230
    • Publication Date:
      20240829
    • Accession Number:
      10.1021/acs.analchem.5b04311
    • Accession Number:
      26754356