Determination of arylamines and aminopyridines in pharmaceutical products using in-situ derivatization and liquid chromatography-mass spectrometry.
J Chromatogr A
; 1216(16): 3563-70, 2009 Apr 17.
Article
em En
| MEDLINE
| ID: mdl-18804773
ABSTRACT
Arylamines and aminopyridines form a class of potentially genotoxic impurities (PGIs) that can be present at trace levels in active pharmaceutical ingredients (APIs). A generic method was developed that allows the analysis of a selected set of these solutes at sub-ppm level relative to the drug substance. A highly concentrated solution of the pharmaceutical compound is analyzed by LC-MS using a single quadrupole mass spectrometer in the selected ion monitoring (SIM) mode. Since a number of target compounds show little or no retention in the reversed-phase LC setup, a fast and simple derivatization procedure using hexylchloroformate was applied. The amide derivatives of the PGI result in a higher molecular weight (more specific ion for SIM) and better chromatographic behavior. The methodology, consisting of a dual run on respectively a non-derivatized and a derivatized sample, was validated and applied to a selection of pharmaceutical substances. The method was found to be sufficiently sensitive and robust and is applicable in a QA/QC environment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Espectrometria de Massas
/
Preparações Farmacêuticas
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Cromatografia Líquida
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Aminas
/
Aminopiridinas
Idioma:
En
Revista:
J Chromatogr A
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Bélgica