RESUMO
Four impurities were detected in candesartan cilexetil bulk drug samples by HPLC and LC/MS. These impurities were marked as CDC-I, II, III and IV. One of the impurities CDC-II was unknown and has not been reported previously. An optimized method using liquid chromatography coupled with electrospray ionization ion trap mass spectrometry (LC/ESI-ITMS) in positive ion mode has been developed to carry out structural identification of unknown impurity. Based on mass spectrometric data and synthetic specifics the structure of CDC-II was proposed as 2-ethoxy-1-[[2'-(1-ethyl-1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylic acid ethyl ester. The impurity was isolated by semi-preparative HPLC and structure was confirmed by NMR spectroscopy. The plausible mechanism for the formation of impurities is also discussed.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/análise , Benzimidazóis/análise , Compostos de Bifenilo/análise , Cromatografia Líquida , Contaminação de Medicamentos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray , Tecnologia Farmacêutica/métodos , Tetrazóis/análise , Bloqueadores do Receptor Tipo 1 de Angiotensina II/síntese química , Benzimidazóis/síntese química , Compostos de Bifenilo/síntese química , Química Farmacêutica , Composição de Medicamentos , Esterificação , Estrutura Molecular , Controle de Qualidade , Espectrofotometria Ultravioleta , Tetrazóis/síntese químicaRESUMO
Three impurities were detected in escitalopram bulk drug by HPLC-UV and LC/MS. These impurities were marked as ESC-I, -II and -III. Two of these impurities (ESC-II and -III) were unknown and have not been reported previously. Ion trap and Q-TOF mass analyzer were employed to carry out MS/MS and accurate mass analysis of these unknown impurities. Based on mass spectrometric data and synthetic specifics the structures of ESC-II and -III were proposed as N-(chloromethyl)-3-[5-cyano-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-1-yl]-N,N-dimethylpropan-1-aminium and N-(chloromethyl)-4-[4-cyano-2-(hydroxymethyl)phenyl]-4-(4-fluorophenyl)-4-hydroxy-N,N-dimethylbutan-1-aminium respectively. The impurities were isolated by semi-preparative HPLC and structures were confirmed by NMR spectroscopy. The plausible mechanism for the formation of impurities is also discussed.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Citalopram/análise , Contaminação de Medicamentos , Espectroscopia de Ressonância Magnética/métodos , Inibidores Seletivos de Recaptação de Serotonina/análise , Espectrometria de Massas por Ionização por Electrospray/métodosRESUMO
A major process-related impurity associated with the synthesis of ezetimibe was detected by LC-MS. The isolated impurity was found not to have been previously reported. Based on LC/MS/MS studies and accurate mass data, the structure of that impurity was proposed to be 2-(4-hydroxybenzyl)-N,5-bis-(4-fluorophenyl)-5-hydroxypentanamide. The postulated structure was unambiguously confirmed with the help of the NMR and IR analyses of a synthetically obtained sample. The chemical shift of the labile proton of that new entity was assigned by a 2D-NOESY NMR experiment. A rationalization for the formation of this impurity is provided.
Assuntos
Azetidinas/química , Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , Contaminação de Medicamentos , Hipolipemiantes/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas em Tandem , Tecnologia Farmacêutica/métodos , Ezetimiba , Estrutura Molecular , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Two impurities were detected in citalopram bulk drug substance by HPLC analysis. A new LC-ESI/MS method was developed for the identification of impurities. One of the impurities was found to be unknown and has not been reported previously. The structure of the unknown impurity was proposed on the basis of MS(n) data obtained using ion trap mass analyzer and accurate mass obtained using Q-TOF mass analyzer. The impurity was isolated by semi-preparative HPLC. The structure of the impurity was confirmed as 1-(1,1-bis (4-fluorophenyl)-1,3-dihydroisobenzofuran-5-yl)-4-(dimethylamino) butan-1-one hydrobromide by using NMR and IR spectroscopy.
