Back to Search Start Over

Preformulation evaluation of selumetinib for topical application: skin distribution and photodegradation analysis using MALDI imaging and LC-MS/MS.

Authors :
Nicol, Edith
Do, Bernard
Vignes, Marina
Annereau, Maxime
Paul, Muriel
Wolkenstein, Pierre
Touboul, David
Secretan, Philippe-Henri
Source :
Pharmaceutical Development & Technology; Oct2024, Vol. 29 Issue 8, p855-861, 7p
Publication Year :
2024

Abstract

Understanding drug behavior within the skin, especially for photosensitive compounds, is crucial for developing effective and safe topical therapies. This study employs Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) and Liquid Chromatography-Mass Spectrometry (LC-MS/MS) to investigate the skin permeation and photostability of selumetinib, a MEK inhibitor used in treating type 1 neurofibromatosis (NF1). The highest amounts of selumetinib in the skin sections were obtained when using the gel formulation, suggesting that it is to be preferred to cream formulations to achieve higher permeation of the drug. Our study also revealed that selumetinib is amenable to photodegradation in ex vivo skin explants, and yields one main degradation product, whose degradation is likely triggered by hydrogen abstraction. MALDI-MSI results showed selumetinib and its degradation product concentrate in skin appendages, indicating these structures might serve as drug reservoirs, potentially prolonging retention and efficacy. This study demonstrates that combining MALDI-MSI with LC/MS-MS can highly contribute to the characterization of the fate of photosensitive compounds in the skin, an essential prerequisite to the development of compound-specific photoprotective measures. It will also pave the way for innovative topical delivery strategies for NF1 treatment. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
10837450
Volume :
29
Issue :
8
Database :
Complementary Index
Journal :
Pharmaceutical Development & Technology
Publication Type :
Academic Journal
Accession number :
180359608
Full Text :
https://doi.org/10.1080/10837450.2024.2405829