Identification and in vitro genotoxicity assessment of forced degradation products of glimepiride and glyburide using HEK cell-based COMET assay.
comet assay
glimepiride
glyburide
in silico genotoxicity
stability studies
Journal
Biomedical chromatography : BMC
ISSN: 1099-0801
Titre abrégé: Biomed Chromatogr
Pays: England
ID NLM: 8610241
Informations de publication
Date de publication:
10 Oct 2024
10 Oct 2024
Historique:
revised:
13
09
2024
received:
29
04
2024
accepted:
26
09
2024
medline:
10
10
2024
pubmed:
10
10
2024
entrez:
10
10
2024
Statut:
aheadofprint
Résumé
This study focuses on characterizing the forced degradation products of antidiabetic drugs glimepiride (GMD) and glyburide (GBD), with previously unexplored genotoxicity. Drugs underwent stress induced by acid, base, and hydrogen peroxide. For GMD, impurities were profiled and isolated using Hypersil Gold C8 (250 × 10 mm, 5 μ) through semi-preparative HPLC with a fraction collector. For GBD, impurity profiling was performed using semi-preparative HPLC (Hypersil GOLD C18, 250 × 10 mm, 5 μ), and reverse-phase flash chromatography (FP ECOFLEX C18 4 g column) for isolation. Although five GMD and three GBD impurities were detected, only three GMD and two GBD impurities were separated and assessed for purity using analytical RP-HPLC with the purity percentages ranging from 96.6% to 99.9%. LC-Orbitrap MS was used to identify these three GMD impurities (m/z: 408.122, 338.340, 381.160) and two GBD impurities (m/z: 369.065, 325.283). ProTox-II in silico predictions classified all impurities as class 4 and 5, with no positive genotoxicity indications. In vitro comet assays, using HEK cells, indicated that for GMD, impurity 2 and impurity 5 were less genotoxic, whereas impurity 4 exhibited genotoxicity. For GBD, both impurities 1 and 3 were found to be genotoxic, with impurity 3 showing a higher level of genotoxicity than impurity 1.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e6025Informations de copyright
© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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