RESUMEN
Designing drug candidates exhibiting polypharmacology is one of the strategies adopted by medicinal chemists to address multifactorial diseases. Metabolic disease is one such multifactorial disorder characterized by hyperglycaemia, hypertension and dyslipidaemia among others. In this paper we report a new class of molecular framework combining the pharmacophoric features of DPP4 inhibitors with those of ACE inhibitors to afford potent dual inhibitors of DPP4 and ACE.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Síndrome Metabólico/tratamiento farmacológico , Inhibidores de la Enzima Convertidora de Angiotensina/química , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Animales , Inhibidores de la Dipeptidil-Peptidasa IV/química , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Perros , Humanos , Concentración 50 Inhibidora , Ratones , Microsomas Hepáticos/efectos de los fármacos , Simulación del Acoplamiento Molecular , RatasRESUMEN
A stability-indicating ultra-performance liquid chromatography method was developed and validated for the simultaneous determination of a fixed dose combination of atorvastatin and ezetimibe in bulk drugs. The developed method was successfully applied to the simultaneous quantitative analysis of the combination drugs in tablet. The chromatographic separation was performed on a Kromasil Eternity C18 UHPLC column (2.5 µm, 2.1 × 50 mm) using a gradient elution of acetonitrile and ammonium acetate buffer (pH 6.70; 0.01M) as the mobile phase at a flow rate of 0.2 mL/min with column oven temperature of 40°C. Ultraviolet detection was performed at 245 nm. Total run time was 5 min, within which the primary compounds and their degradation products were separated. The method was validated for accuracy, repeatability, reproducibility and robustness. Linearity, limit of detection and limit of quantitation were established for atorvastatin and ezetimibe.
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Azetidinas/análisis , Azetidinas/química , Cromatografía Líquida de Alta Presión/métodos , Ácidos Heptanoicos/análisis , Ácidos Heptanoicos/química , Pirroles/análisis , Pirroles/química , Anticolesterolemiantes/análisis , Anticolesterolemiantes/química , Atorvastatina , Combinación de Medicamentos , Estabilidad de Medicamentos , Ezetimiba , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Comprimidos/análisis , Comprimidos/químicaRESUMEN
High efficiency and less run time are the basic requirements of high-speed chromatographic separations. To fulfill these requirements, a new separation technique, ultra-performance liquid chromatography (UPLC), has shown promising developments. A rapid, specific, sensitive, and precise reverse-phase UPLC method is developed for the determination of nabumetone in tablet dosage form. In this work, a new isocratic chromatographic method is developed. The newly developed method is applicable for assay determination of the active pharmaceutical ingredient. The chromatographic separation is achieved on a Waters Acquity BEH column (100 mm, i.d., 2.1 mm, 1.7 µm) within a short runtime of 2 min using a mobile phase of 5 mM ammonium acetate-acetonitrile (25:75, v/v), at a flow rate of 0.3 mL/min at an ambient temperature. Quantification is achieved with photodiode array detection at 230 nm, over the concentration range of 0.05-26 µg/mL. Forced degradation studies are also performed for nabumetone bulk drug samples to demonstrate the stability-indicating power of the UPLC method. Comparison of system performance with conventional high-performance liquid chromatography is made with respect to analysis time, efficiency, and sensitivity. The method is validated according to the ICH guidelines and is applied successfully for the determination of nabumetone in tablets.
Asunto(s)
Butanonas/análisis , Cromatografía Liquida/métodos , Inhibidores de la Ciclooxigenasa 2/análisis , Comprimidos , Formas de Dosificación , Límite de Detección , Nabumetona , Estándares de Referencia , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: Venlafaxine,hydrochloride is a structurally novel phenethyl bicyclic antidepressant, and is usually categorized as a serotonin-norepinephrine reuptake inhibitor (SNRI) but it has been referred to as a serotonin-norepinephrine-dopamine reuptake inhibitor. It inhibits the reuptake of dopamine. Venlafaxine HCL is widely prescribed in the form of sustained release formulations. In the current article we are reporting the development and validation of a fast and simple stability indicating, isocratic high performance liquid chromatographic (HPLC) method for the determination of venlafaxine hydrochloride in sustained release formulations. MATERIALS AND METHODS: The quantitative determination of venlafaxine hydrochloride was performed on a Kromasil C18 analytical column (250 × 4.6 mm i.d., 5 µm particle size) with 0.01 M phosphate buffer (pH 4.5): methanol (40: 60) as a mobile phase, at a flow rate of 1.0 ml/min. For HPLC methods, UV detection was made at 225 nm. RESULTS: During method validation, parameters such as precision, linearity, accuracy, stability, limit of quantification and detection and specificity were evaluated, which remained within acceptable limits. CONCLUSIONS: The method has been successfully applied for the quantification and dissolution profiling of Venlafaxine HCL in sustained release formulation. The method presents a simple and reliable solution for the routine quantitative analysis of Venlafaxine HCL.
RESUMEN
OBJECTIVE: Arterolane maleate is an antimalarial drug currently under Phase III clinical evaluation, and presents a simple, economical and scalable synthesis, and does not suffer from safety problems. Arterolane maleate is more active than artemisinin; and is cheap to produce. It has a longer lifetime in the plasma, so it stays active longer in the body. To provide quality control over the manufacture of any API, it is essential to develop highly selective analytical methods. In the current article we are reporting the development and validation of a rapid and specific Head space gas chromatographic (HSGC) method for the determination of organic volatile impurities (residual solvents) in Arterolane Maleate bulk drug. MATERIALS AND METHODS: The method development and its validation were performed on Perkin Elmer's gas chromatographic system equipped with Flame Ionization detector and head space analyzer. The method involved a thermal gradient elution of ten residual solvents present in arterolane maleate salt in RTx-624, 30 m × 0.32 mm, 1.8 µ column using nitrogen gas as a carrier. The flow rate was 0.5 ml/min and flame ionization detector (FID) was used. RESULTS: During method validation, parameters such as precision, linearity, accuracy, limit of quantification and detection and specificity were evaluated, which remained within acceptable limits. CONCLUSIONS: The method has been successfully applied for the quantification of the amount of residual solvents present in arterolane maleate bulk drug.The method presents a simple and reliable solution for the routine quantitative analysis of residual solvents in Arterolane maleate bulk drug.
RESUMEN
The present study describes the development and subsequent validation of a stability indicating reverse-phase HPLC (RP-HPLC) method for the analysis of oseltamivir active pharmaceutical ingredient (API). The proposed RP-HPLC method utilizes Kromasil C(18), 5 microm, 250 mm x 4.6 mm i.d. column (at ambient temperature), gradient run (using acetonitrile and triethylamine as mobile phase), effluent flow rate (1.0 ml/min), and UV detection at 215 nm for analysis of oseltamivir. The described method was linear over the range of 70-130 microg/ml (r(2)=0.999). The precision, ruggedness and robustness values were also within the prescribed limits (<1% for system precision and <2% for other parameters). Oseltamivir was exposed to acidic, basic, oxidative and thermal stress conditions, and the stressed samples were analyzed by the proposed method. Chromatographic peak purity results indicated the absence of co-eluting peaks with the main peak of oseltamivir, which demonstrated the specificity of assay method for estimation of oseltamivir in presence of degradation products. The proposed method can be used for routine analysis of oseltamivir in quality control laboratories.