title: Discovery of a novel trimebutine metabolite and its impact on N-desmethyltrimebutine quantification by LC-MS/MS.
abstract: BACKGROUND
  A failure in incurred sample reanalysis (ISR) for N-desmethyltrimebutine (NDMT), during the analysis of a trimebutine-containing drug GIC-1001 Phase I study, led to the discovery of a never-before reported metabolite of trimebutine.
  
  
  RESULTS
  A positive bias for NDMT during the ISR and post-reconstitution stability evaluations indicated the presence of an unstable metabolite of NDMT. Precursor ion scans performed on freshly extracted samples enabled the identification of this metabolite to be the NDMT glucuronide conjugate and its fragmentation pattern suggested that the glucuronide moiety was attached at the N-terminal of NDMT.
  
  
  CONCLUSIONS
  An acidification step was introduced in the extraction procedure to completely hydrolyze the glucuronide and measure the total NDMT in plasma, rendering this method a successful fit-for-purpose assay.
authors.affiliation: Algorithme Pharma Inc., 575 Armand-Frappier, Laval, QC H7V 4B3, Canada.
authors.forename: Hélène
authors.initials: H
authors.lastname: Montpetit
authors.forename: Maxime
authors.initials: M
authors.lastname: Ranger
authors.forename: Patrick
authors.initials: P
authors.lastname: Colin
authors.forename: Milton
authors.initials: M
authors.lastname: Furtado
authors.forename: Fabio
authors.initials: F
authors.lastname: Garofolo
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D017321:Clinical Trials, Phase I as Topic; D055808:Drug Discovery; D020719:Glucuronides / Q000737:chemistry*; D064368:Healthy Volunteers; D006801:Humans; D006868:Hydrolysis; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014287:Trimebutine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism*
chemical_list: D020719:Glucuronides; C053065:N-desmethyltrimebutine; D014287:Trimebutine