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

Helene Montpetit has a Bachelor of Science in Biochemistry from the University du Quebec 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 i...