Identification of the Major Degradation Pathways of Selumetinib
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 selume...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/12/2651 |
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| author | Tahar Sif eddine Bouchema Maxime Annereau Victoire Vieillard Raphael Boquet Gisele Abreu Coelho Florence Castelli Audrey Solgadi Muriel Paul Najet Yagoubi Philippe-Henri Secretan Bernard Do |
| author_facet | Tahar Sif eddine Bouchema Maxime Annereau Victoire Vieillard Raphael Boquet Gisele Abreu Coelho Florence Castelli Audrey Solgadi Muriel Paul Najet Yagoubi Philippe-Henri Secretan Bernard Do |
| author_sort | Tahar Sif eddine Bouchema |
| collection | DOAJ |
| description | 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-HRMS<sup>n</sup>. 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. |
| first_indexed | 2024-03-09T15:58:12Z |
| format | Article |
| id | doaj.art-3af45a625be546e5b1670badf7227520 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T15:58:12Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-3af45a625be546e5b1670badf72275202023-11-24T17:19:40ZengMDPI AGPharmaceutics1999-49232022-11-011412265110.3390/pharmaceutics14122651Identification of the Major Degradation Pathways of SelumetinibTahar Sif eddine Bouchema0Maxime Annereau1Victoire Vieillard2Raphael Boquet3Gisele Abreu Coelho4Florence Castelli5Audrey Solgadi6Muriel Paul7Najet Yagoubi8Philippe-Henri Secretan9Bernard Do10Matériaux et Santé, Université Paris-Saclay, 91400 Orsay, FranceMatériaux et Santé, Université Paris-Saclay, 91400 Orsay, FranceDepartment of Pharmacy, Henri Mondor Hospital, AP-HP, 94000 Créteil, FranceDepartment of Pharmacy, Henri Mondor Hospital, AP-HP, 94000 Créteil, FranceMatériaux et Santé, Université Paris-Saclay, 91400 Orsay, FranceDépartement Médicaments et Technologies pour la Santé (DMTS), MetaboHUB, CEA, INRAE, Université Paris-Saclay, 91191 Gif-sur-Yvette, FranceIngénierie et Plateformes au Service de l’Innovation Thérapeutique, Inserm, CNRS, Université Paris-Saclay, 92296 Châtenay-Malabry, FranceDepartment of Pharmacy, Henri Mondor Hospital, AP-HP, 94000 Créteil, FranceMatériaux et Santé, Université Paris-Saclay, 91400 Orsay, FranceMatériaux et Santé, Université Paris-Saclay, 91400 Orsay, FranceMatériaux et Santé, Université Paris-Saclay, 91400 Orsay, FranceSelumetinib 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-HRMS<sup>n</sup>. 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.https://www.mdpi.com/1999-4923/14/12/2651pre-formulation studiesintrinsic stabilitydegradation pathwaysoxidationphotooxidationprotein kinase inhibitor |
| spellingShingle | Tahar Sif eddine Bouchema Maxime Annereau Victoire Vieillard Raphael Boquet Gisele Abreu Coelho Florence Castelli Audrey Solgadi Muriel Paul Najet Yagoubi Philippe-Henri Secretan Bernard Do Identification of the Major Degradation Pathways of Selumetinib Pharmaceutics pre-formulation studies intrinsic stability degradation pathways oxidation photooxidation protein kinase inhibitor |
| title | Identification of the Major Degradation Pathways of Selumetinib |
| title_full | Identification of the Major Degradation Pathways of Selumetinib |
| title_fullStr | Identification of the Major Degradation Pathways of Selumetinib |
| title_full_unstemmed | Identification of the Major Degradation Pathways of Selumetinib |
| title_short | Identification of the Major Degradation Pathways of Selumetinib |
| title_sort | identification of the major degradation pathways of selumetinib |
| topic | pre-formulation studies intrinsic stability degradation pathways oxidation photooxidation protein kinase inhibitor |
| url | https://www.mdpi.com/1999-4923/14/12/2651 |
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