title: Software-aided structural elucidation in drug discovery.
abstract: BACKGROUND
  Structural information on metabolites obtained in relevant biological systems can have considerable impact on the design of new drug candidates. However, with demanding turnaround times, the amount of available structural information may become rate limiting.
  
  
  METHODS
  The workflow for metabolite identification used in our laboratory was compared to a workflow using a software tool built for computer-assisted metabolite identification. The present study covered the in vitro metabolism of a diverse set of 65 in-house compounds. The compounds were profiled across three liver-based systems, 17 compounds were tested in human liver microsomes (HLM), 12 in rat hepatocytes (RHEP), and 36 in human hepatocytes (HHEP).
  
  
  RESULTS
  For 92% of the metabolites reported, the exact match or Markush representations were in agreement between the two workflows. The major specific biotransformations in hepatocytes which formed the metabolites were aromatic or aliphatic hydroxylations (33%), N-dealkylations (15%) and glucuronidations (12%).
  
  
  CONCLUSIONS
  The software was shown to perform well for structural elucidation of metabolites from both phase I and phase II metabolism where the focus was on quickly understanding the rate-limiting metabolic step(s).
authors.affiliation: Cardiovascular & Metabolic Diseases iMED DMPK, Innovative Medicines, AstraZeneca R&D Mölndal, 431 83, Mölndal, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Ahlqvist
authors.affiliation: Cardiovascular & Metabolic Diseases iMED DMPK, Innovative Medicines, AstraZeneca R&D Mölndal, 431 83, Mölndal, Sweden.
authors.forename: Carina
authors.initials: C
authors.lastname: Leandersson
authors.affiliation: Cardiovascular & Metabolic Diseases iMED DMPK, Innovative Medicines, AstraZeneca R&D Mölndal, 431 83, Mölndal, Sweden.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Hayes
authors.affiliation: Lead Molecular Design, S.L. Av. Cedanyola 92-94, 08173, Sant Cugat del Vallés, Spain.|Pompeu Fabra University, Dr. Aiguader 88, 08008, Barcelona, Spain.
authors.forename: Ismael
authors.initials: I
authors.lastname: Zamora
authors.affiliation: Respiratory, Inflammation & Autoimmunity iMED DMPK, Innovative Medicines, AstraZeneca R&D Mölndal, 431 83, Mölndal, Sweden.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Thompson
mesh_terms: D000818:Animals; D055808:Drug Discovery; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D012984:Software
chemical_list: D004364:Pharmaceutical Preparations