RT info:eu-repo/semantics/article
T1 Identification and quantitation of cis-ketoconazole impurity by capillary zone electrophoresis-mass spectrometry
A1 Castro Puyana, María
A1 García Ruiz, Carmen
A1 Cifuentes Gallego, Alejandro
A1 Crego Navazo, Antonio Luis
A1 Marina Alegre, María Luisa
K1 Cis-Ketoconazole
K1 Trans-Ketoconazole
K1 CE-MS
K1 Impurity
K1 Pharmaceutical formulations
K1 Ciencia
K1 Química analítica e industrial
K1 Science
K1 Chemistry, analytic and technical
AB 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.
PB Elsevier
SN 0021-9673
YR 2006
FD 2006
LK http://hdl.handle.net/10017/1347
UL http://hdl.handle.net/10017/1347
LA eng
NO Authors thank the Ministry of Science and Technology (Spain) for the research project BQU2003-03638. CarmenGarcía-Ruiz thanks the Ministry of Science and Technology forthe Ramón y Cajal program (RYC-2003-001). María CastroPuyana thanks the University of Alcala for her pre-doctoral grant.
DS MINDS@UW
RD 27-abr-2024