RESUMO
A simple, sensitive, and stability indicating isocratic reverse phase high performance liquid chromatography method has been developed, optimized and validated for the separation and quantification of S-enantiomer in linagliptin (R-enantiomer) drug substance. Enantiomeric separation was achieved on a Cellulose tris(4-chloro-3-methylphenylcarbamate) stationary phase. Mobile phase consists of aqueous diammonium hydrogen phosphate buffer and acetonitrile in the ratio of 35:65 v/v. Isocratic elution was performed at a flow rate of 1.0 mL/min, the column oven temperature was set at 40°C and detection was at 226 nm. The resolution between R and S enantiomers is found to be more than 4.0. The impact of mobile phase composition, pH of buffer and temperature on the resolution has been studied. The detector response is found to be linear over the concentration range of 0.17-1.7 µg/mL. LOD and LOQ levels of S-enantiomer are found to be 0.057 and 0.172 µg/mL respectively. The recovery of S-enantiomer is 99.8% w/w. The proposed method is validated for specificity, precision, linearity, accuracy and robustness.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa/métodos , Inibidores da Dipeptidil Peptidase IV/análise , Linagliptina/análise , Acetonitrilas/química , Celulose/química , Limite de Detecção , Fosfatos/química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estereoisomerismo , TemperaturaRESUMO
During the synthesis of ezetimibe, two process related impurities were detected were HPLC analysis at levels ranging from 0.05 to 0.8%. These two impurities were isolated by column chromatography and co-injected with ezetimibe sample to confirm the retention times in HPLC. These two impurities were characterized as 2-(4-hydroxybenzyl)-N,5-bis(4-fluorophenyl) pentanamide (impurity-I) and 1-(4-fluorophenyl)-3(3-(4-fluorophenyl)propyl)-4-(4-hydroxyphenyl)azetidin-2-one (impurity-II). Isolation, structural elucidation of these impurities by spectral data ((1)H NMR, (13)C NMR, MS and IR) and probable mechanism of their formation have been discussed.
Assuntos
Anticolesterolemiantes/química , Azetidinas/química , Acetonitrilas/química , Anticolesterolemiantes/análise , Azetidinas/análise , Química Farmacêutica , Colesterol/química , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Contaminação de Medicamentos , Ezetimiba , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Ácidos Fosfóricos/química , Espectrofotometria Infravermelho , Espectroscopia de Infravermelho com Transformada de Fourier , Tecnologia FarmacêuticaRESUMO
Impurities found in stressed and stability studies of olanzapine (polymorphic form-I) [1-7] in both drug substance and drug product are described. These impurities are identified as 4-(4-methyl-1-piperazinyl)-3-hydroxymethylidene-1H-benzo[b][1,4]diazepine-2(3H)-thione (hydroxymethylidene thione) and (Z)-4-(4-methyl-1-piperazinyl)-3-acetoxymethylidene-1H-benzo[b][1,4]diazapine-2(3H)-thione (acetoxymethylidene thione). An oxidative degradation pathway of olanzapine, for the formation of these impurities, has been proposed.
Assuntos
Antipsicóticos/análise , Benzodiazepinas/análise , Contaminação de Medicamentos , Antipsicóticos/química , Benzodiazepinas/química , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Excipientes/análise , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Olanzapina , Oxirredução , Comprimidos , Espectrometria de Massas em Tandem , Tecnologia Farmacêutica/métodosRESUMO
A new degradant of sultamicillin drug substance was found during the gradient reverse phase HPLC analysis of stability storage samples. The level of this degradant impurity was observed up to 1.0%. The impurity (formaldehyde adduct with 5-oxo-4-phenylimidazolidin-1-yl moiety) was identified by LC/MS and was characterized by ((1)H NMR, (13)C NMR, 2D-NMR ((1)H-(1)H COSY, NOESY, HSQC and HMBC), LC/MS/MS, MS/TOF, elemental analysis and IR. This impurity was prepared by isolation and co-injected into HPLC system to confirm the retention time.
Assuntos
Contaminação de Medicamentos , Pneumonia/tratamento farmacológico , Ampicilina/análise , Ampicilina/química , Ampicilina/farmacologia , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Estabilidade de Medicamentos , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Espectrofotometria Infravermelho , Sulbactam/análise , Sulbactam/química , Sulbactam/farmacologia , Espectrometria de Massas em TandemRESUMO
Rabeprazole sodium [1] is a proton pump inhibitor, used as an antiulcerative. During the manufacturing of rabeprazole sodium, we observed an unknown impurity at levels 0.05-0.1% in HPLC analysis along with the known potential impurities. This new unknown impurity was isolated using preparative liquid chromatography. Based on the complete spectral analysis ((1)H NMR, (13)C NMR, DEPT, Mass and IR), this new impurity was designated as 2-[[(3-methyl-4-(methylthio)-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole (methylthio impurity of rabeprazole). Impurity isolation, structure elucidation and probable formation mechanism was discussed.