Trace-level determination of potential genotoxic impurities in quetiapine fumarate using LC-MS.
2-(2-aminophenylthio)benzoicacid hydrochloride
2-(2-aminophenylthio)benzonitrile
2-aminothiophenol
LC-MS
genotoxic impurities
quetiapine fumarate
Journal
Biomedical chromatography : BMC
ISSN: 1099-0801
Titre abrégé: Biomed Chromatogr
Pays: England
ID NLM: 8610241
Informations de publication
Date de publication:
Apr 2023
Apr 2023
Historique:
revised:
08
12
2022
received:
01
12
2022
accepted:
19
12
2022
pubmed:
22
12
2022
medline:
17
3
2023
entrez:
21
12
2022
Statut:
ppublish
Résumé
A novel LC-MS method was developed and validated to determine three potential genotoxic impurities, namely 2-(2-aminophenylthio)benzoic acid hydrochloride, 2-aminothiophenol, and 2-(2-aminophenylthio)benzonitrile, at trace level (~1.6 ppm) in quetiapine fumarate drug substance, an antipsychotic drug. These impurities are potentially genotoxic and therefore should be controlled at or below specific acceptance limits. An InertSustain AQ-C18 column (250 × 4.6 mm, 5 μm) in reversed-phase mode with the column temperature at 45°C was used. The mobile phase was 0.1% trifluoroacetic acid in water and acetonitrile with gradient elution mode, and the run time was 45 min. The flow rate was 0.8 ml/min. A mass spectrometer was used to quantify the amount of impurities using electrospray ionization mode at specific m/z 245.9, 126.0, and 226.9 for 2-(2-aminophenylthio)benzoic acid hydrochloride, 2-aminothiophenol, and 2-(2-aminophenylthio) benzonitrile, respectively. The method was found to be sensitive and possessed excellent linearity in the concentration ranges from the limit of quantification to 150% of the permitted level (0.47-2.36 μg/ml) with correlation coefficients above 0.999. The results showed that the method was specific, precise, linear, and accurate for the estimation of these three impurities in quetiapine fumarate.
Substances chimiques
benzonitrile
9V9APP5H5S
2-aminothiophenol
137-07-5
Quetiapine Fumarate
2S3PL1B6UJ
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e5575Informations de copyright
© 2022 John Wiley & Sons Ltd.
Références
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