RESUMO
Several related substances (RS4-RS10) were detected in lopinavir drug substance at levels ranging from 0.03% to 0.1% by employing gradient RP-HPLC. The related substances were identified by LC-MS analysis. These related substances were isolated and characterized by Mass, (1)H NMR and FT-IR spectral data. The separation was achieved on a YMC Pack ODS-AQ (250 mm x 4.6 mm, 5 microm) column thermostated at 45 degrees C using 0.02 M KH(2)PO(4) (pH 2.5): acetonitrile as a mobile phase in gradient elution mode. A PDA detector set at 210 nm was used for detection. The investigated validation elements showed the method has acceptable specificity, accuracy, linearity, precision, robustness and high sensitivity with detection limits and quantitation limits ranging from 0.028 microg/ml to 0.063 microg/ml and 0.084 microg/ml to 0.192 microg/ml respectively. The method can be used for routine quality control analysis and stability testing of lopinavir drug substance.
Assuntos
Contaminação de Medicamentos , Inibidores da Protease de HIV/química , Preparações Farmacêuticas/química , Pirimidinonas/química , Soluções Tampão , Cromatografia Líquida de Alta Pressão/instrumentação , Cromatografia Líquida de Alta Pressão/métodos , Estabilidade de Medicamentos , Guias como Assunto , Inibidores da Protease de HIV/análise , Inibidores da Protease de HIV/síntese química , Concentração de Íons de Hidrogênio , Lopinavir , Espectrometria de Massas , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Preparações Farmacêuticas/análise , Fosfatos/química , Compostos de Potássio/química , Pirimidinonas/análise , Pirimidinonas/síntese química , Controle de Qualidade , Padrões de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Fatores de Tempo , Água/químicaRESUMO
Three unknown impurities in Cefdinir bulk drug at levels below 0.2% (ranging from 0.05 to 0.2%) have been detected by high performance liquid chromatography (HPLC). These impurities were isolated from crude sample of Cefdinir using preparative HPLC. Based on the spectral data (NMR, IR and MS) the structures of these impurities were characterized as (6R, 7R)-7-[(z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-8-oxo-3-vinyl-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid-5-oxide (I). (6R, 7R)-7-[(z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-8-oxo-3-vinyl-5-thia-1-azabi-cyclo [4.2.0] oct-3-ene-2-carboxylic acid (II). (6R, 7R)-7-[(z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-8-oxo-3-methyl-5-thia-1-azabicyclo-[4.2.0]oct-2-ene-2-carboxylic acid (III), respectively. The origin and structural elucidation of all impurities have been discussed.