Identification and quantitation of cis-ketoconazole impurity by capillary zone electrophoresis-mass spectrometry
Autores
Castro Puyana, María; García Ruiz, Carmen; Cifuentes Gallego, Alejandro; Crego Navazo, Antonio Luis; Marina Alegre, María LuisaIdentificadores
Enlace permanente (URI): http://hdl.handle.net/10017/1347DOI: 10.1016/j.chroma.2006.02.030
ISSN: 0021-9673
Editor
Elsevier
Fecha de publicación
2006Patrocinadores
Authors thank the Ministry of Science and Technology (Spain) for the research project BQU2003-03638. Carmen
García-Ruiz thanks the Ministry of Science and Technology for
the Ramón y Cajal program (RYC-2003-001). María CastroPuyana thanks the University of Alcala for her pre-doctoral
grant.
Cita bibliográfica
Journal of Chromatography A, 2006, v. 1114, p. 170-177
Palabras clave
Cis-Ketoconazole
Trans-Ketoconazole
CE-MS
Impurity
Pharmaceutical formulations
Proyectos
info:eu-repo/grantAgreement/MICYT//BQU2003-03638/ES/CROMATOGRAFÍA ELECTROCINÉTICA: UNA PODEROSA HERRAMIENTA PARA LA SEPARACIÓN ENANTIOMÉRICA DE COMPUESTOS QUIRALES CON APLICACIÓN A LA DETERMINACIÓN DE LA PUREZA ENANTIOMÉRICA
info:eu-repo/grantAgreement/MEC//RYC-2003-001/ES/RYC-2003-001/
Tipo de documento
info:eu-repo/semantics/article
Versión
info:eu-repo/semantics/publishedVersion
Versión del editor
http://dx.doi.org/10.1016/j.chroma.2006.02.030Derechos
(c) Elsevier, 2006
Derechos de acceso
info:eu-repo/semantics/openAccess
Resumen
trans-Ketoconazole was identified and quantified as impurity of cis-ketoconazole, an antifungal compound, by capillary zone electrophoresis–electrospray–mass spectrometry (CZE–ESI–MS). The chirality of this impurity was demonstrated separating their enantiomers by adding heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin to the separation buffer in capillary electrophoresis (CE) with UV detection. However, MS detection was hyphenated to the CE instrument for its identification. As both compounds are diastereomers, they have the same m/z values and are needed to be separated prior to the MS identification. A 0.4 M ammonium formate separation buffer at pH 3.0 enabled the separation of the impurity from cis-ketoconazole. Under these conditions, the optimization of ESI–MS parameters (composition and flow of the sheath–liquid, drying temperature, drying gas flow, and capillary potential) was carried out to obtain the best MS sensitivity. CZE–ESI–MS optimized conditions enabled the identification of trans-ketoconazole as impurity of cis-ketoconazole. In addition, the quantitation of this impurity was achieved in different samples: cis-ketoconazole standard and three different pharmaceutical formulations (two tablets and one syrup) containing this standard. In all cases, percentages higher than 2.0 were determined for the impurity. According to ICH guidelines, these values required the identification and quantitation of any impurity in drug substances and products.
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