Asunto(s)
Antiasmáticos , Anticoagulantes , Antieméticos , Diarrea , Aprobación de Drogas , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Aminopiridinas/análisis , Aminopiridinas/farmacología , Aminopiridinas/uso terapéutico , Antiasmáticos/análisis , Antiasmáticos/farmacología , Antiasmáticos/uso terapéutico , Anticuerpos Monoclonales Humanizados/análisis , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticoagulantes/análisis , Anticoagulantes/farmacología , Anticoagulantes/uso terapéutico , Antieméticos/análisis , Antieméticos/farmacología , Antieméticos/uso terapéutico , Benzodioxoles/análisis , Benzodioxoles/farmacología , Benzodioxoles/uso terapéutico , Colagogos y Coleréticos/análisis , Colagogos y Coleréticos/farmacología , Colagogos y Coleréticos/uso terapéutico , Regulador de Conductancia de Transmembrana de Fibrosis Quística/análisis , Regulador de Conductancia de Transmembrana de Fibrosis Quística/farmacología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/uso terapéutico , Ácido Desoxicólico/análisis , Ácido Desoxicólico/farmacología , Ácido Desoxicólico/uso terapéutico , Diarrea/tratamiento farmacológico , Imidazoles/análisis , Imidazoles/farmacología , Imidazoles/uso terapéutico , Síndrome del Colon Irritable/fisiopatología , Compuestos de EspiroRESUMEN
The simple and low cost ß-cyclodextrin (ß-CD)-phenolphthalein (PHP) inclusion complex was used for both the study of physical-chemical parameters and validation of analytical procedures for deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) determinations in different formulations. The usefulness of this inclusion complex is proposed either in the form of kit reagent and as an original optical sensor for DCA and UDCA. The results showed that temperature had a negative effect on the equilibrium constant resulting in high negative values of enthalpy and positive values of entropy. The half-life values for DCA and UDCA measurements were 68.71 and 294.71 days, respectively. The method was validated showing limits of detection and quantification of 4.92×10(-5) mol L(-1) and 1.64×10(-4) mol L(-1) for DCA, 1.14×10(-5) mol L(-1) and 3.79×10(-5) mol L(-1) for UDCA, respectively. The developed optical sensor also showed response linearity, ease of implementation and potential application in fast screening tasks even out of the laboratory.
Asunto(s)
Fenómenos Químicos , Técnicas de Química Analítica/instrumentación , Colorimetría/métodos , Ácido Desoxicólico/análisis , Fenómenos Ópticos , Ácido Ursodesoxicólico/análisis , Ácidos y Sales Biliares/análisis , Colorimetría/economía , Ácido Desoxicólico/química , Entropía , Indicadores y Reactivos/química , Fenolftaleína/química , Juego de Reactivos para Diagnóstico , Temperatura , Factores de Tiempo , Ácido Ursodesoxicólico/química , beta-Ciclodextrinas/químicaRESUMEN
An expeditious colorimetric methodology for the determination of the deoxycholic acid (DCA) and of the ursodeoxycholic acid (UDCA) in pharmaceutical formulations is reported. The method is based on their competitive complexation reaction with a color indicator to form beta-cyclodextrin-inclusion complexes. Several pH color indicators were tested, but phenolphthalein (PHP) showed the best interaction with the beta-cyclodextrin (beta-CD) with an inclusion yield higher than 95%. The best concentrations of beta-cyclodextrin to form inclusion complexes were 1.24 x 10(-3) and 6.2 x 10(-4) M at pH 9.5 and 10.5. Statistical analysis of the results showed that the pH had a significant effect on the DCA determination and that high beta-CD-PHP inclusion complex concentrations had a significant negative effect on the UDCA determination (p < 0.05). The limit of detection and limit of quantification were 3.94 x 10(-5) and 1.31 x 10(-4) M for DCA (range: 6.1 x 10(-6)-3.13 x 10(-3) M), 4.08 x 10(-5) and 1.36 x 10(-4) M for UDCA (range: 6.05 x 10(-6)-3.88 x 10(-4) M). This simple and cheap method showed high stability and feasible instrumentation.
Asunto(s)
Ácido Desoxicólico/análisis , Fenolftaleína/química , Ácido Ursodesoxicólico/análisis , beta-Ciclodextrinas/química , Límite de DetecciónRESUMEN
A cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) method has been developed and validated for purity determination of two bile acids, ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA). Quantitation of related impurities such as lithocholic acid (LCA), chenodeoxycholic acid (CDCA), cholic acid (CA), and DCA in UDCA and CA in DCA was performed. A running buffer containing 20 mM borate-phosphate, 50 mM sodium dodecyl sulfate (SDS), 2.0 mM beta-cyclodextrin, and acetonitrile was used. Modifiers were added to improve resolution and selectivity. The applied voltage was 25 kV and detection was performed at 185 nm. Validation parameters such as selectivity, linearity, repeatability, intermediate precision, limit of detection, limit of quantitation, and robustness were evaluated. The method was simple and proved to be useful for the purity testing of bile acids in bulk drugs. Good results were obtained for related impurities at concentration levels from 0.05 to 1.5% with respect to the main component, according to international requirements.
Asunto(s)
Cromatografía Capilar Electrocinética Micelar/métodos , Ciclodextrinas , Ácido Desoxicólico/análisis , Ácido Ursodesoxicólico/análisis , beta-Ciclodextrinas , Cromatografía Capilar Electrocinética Micelar/normas , Estructura MolecularRESUMEN
The modification in the composition of bile acids in hamster by the administration of high dose of ursodeoxycholic acid (UDCA) was investigated. Male Golden Syrian hamsters were divided into five groups: a control group, two groups that received 0.5 g of UDCA per 100 g of standard diet during 30 and 60 days and another two groups that received 1 g of UDCA per 100 g of standard diet during 30 and 60 days. After ether anaesthesia the gallbladder was removed and bile was immediately aspirated. Bile acids were determined by high performance liquid chromatography (HPLC). Taurolithocholic (TLCA) and glycolithocholic acids (GLCA) increased significantly in all treated groups. The glyco/tauro ratio of 0.69 in controls became more than 1 in treated animals except in the case of lithocholic acid (LCA) conjugates which remained less than 1. UDCA derivatives increased proportionally to the administered dose and the cholic/cheno ratio diminished significantly. A moderate increase of 3- and 7-keto derivatives of chenodeoxycholic acid (CDCA) was observed in all treated groups but the above mentioned increment was especially evident in 3-keto derivatives. A high percentage of UDCA administered in the hamster was likely transformed to CDCA and the glyco conjugates of the bile acids were the predominant species except for the LCA derivatives.