Discovery of a novel trimebutine metabolite and its impact on N-desmethyltrimebutine quantification by LC–MS/MS

Author:

Montpetit Hélène1,Ranger Maxime2,Colin Patrick2,Furtado Milton1,Garofolo Fabio1

Affiliation:

1. Algorithme Pharma Inc., 575 Armand-Frappier, Laval, QC H7V 4B3, Canada

2. gIcare Pharma Inc., 227 Ave Westminster North, Montreal-West, QC H4X 1Z5, Canada

Abstract

Hélène Montpetit has a Bachelor of Science in Biochemistry from the University du Québec at Montreal. For the past 15 years, she has worked in the bioanalysis field in CROs environment as well as in a big Pharma. She currently holds a position as scientific reviewer in the method development group at Algorithme Pharma. 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.

Publisher

Future Science Ltd

Subject

Medical Laboratory Technology,Clinical Biochemistry,General Pharmacology, Toxicology and Pharmaceutics,General Medicine,Analytical Chemistry

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