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Identification of the Major Degradation Pathways of Selumetinib.

ABSTRACT: Selumetinib is administered orally in capsule form and is indicated for the treatment of neurofibromatosis. To facilitate dosage adjustments, liquid preparations, such as solutions or suspensions, are to be developed. This led, first, to determine the stability profile of soluble or dispersed selumetinib and, secondly, to look for ways to stabilize the active substance. The degradation kinetics of selumetinib as a function of stress conditions were determined and compared. The degradation products were detected and identified by LC-HRMSⁿ. In solution, selumetinib is sensitive to oxidation and degrades by photooxidation. In both cases, the side chain represented by the oxoamide group is concerned, leading to the formation of an amide derivative for the first case and an ester derivative for the second. The identification of such degradation mechanisms allowed us to study, in a targeted way, processes aiming at stabilizing the active molecule.

SUBMITTER: Bouchema TSE

PROVIDER: S-EPMC9787286 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Identification of the Major Degradation Pathways of Selumetinib.

Bouchema Tahar Sif Eddine TSE Annereau Maxime M Vieillard Victoire V Boquet Raphael R Coelho Gisele Abreu GA Castelli Florence F Solgadi Audrey A Paul Muriel M Yagoubi Najet N Secretan Philippe-Henri PH Do Bernard B

Pharmaceutics 20221130 12

Selumetinib is administered orally in capsule form and is indicated for the treatment of neurofibromatosis. To facilitate dosage adjustments, liquid preparations, such as solutions or suspensions, are to be developed. This led, first, to determine the stability profile of soluble or dispersed selumetinib and, secondly, to look for ways to stabilize the active substance. The degradation kinetics of selumetinib as a function of stress conditions were determined and compared. The degradation produc ...[more]

PMID: 36559146

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Identification of the Major Degradation Pathways of Selumetinib.

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Identification of the Major Degradation Pathways of Selumetinib.

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