ABSTRACT
The present work focused on the application of design of experiment (DoE) principles to the development and optimization of a stability-indicating method (SIM) for the drug imidapril hydrochloride and its degradation products (DPs). The resolution of peaks for the DPs and their drug in a SIM can be influenced by many factors. The factors studied here were pH, gradient time, organic modifier, flow rate, molar concentration of the buffer, and wavelength, with the aid of a Plackett-Burman design. Results from the Plackett-Burman study conspicuously showed influence of two factors, pH and gradient time, on the analyzed response, particularly, the resolution of the closely eluting DPs (DP-5 and DP-6) and the retention time of the last peak. Optimization of the multiresponse processes was achieved through Derringer's desirability function with the assistance of a full factorial design. Separation was achieved using a C18 Phenomenex Luna column (250 × 4.6 mm id, 5 µm particle size) at a flow rate of 0.8 mL/min at 210 nm. The optimized mobile phase composition was ammonium-acetate buffer (pH 5) in pump A and acetonitrile-methanol (in equal ratio) in pump B with a run time of 40 min using a gradient method.
Subject(s)
Chromatography, High Pressure Liquid/methods , Imidazolidines/analysis , Buffers , Chromatography, High Pressure Liquid/instrumentation , Drug Stability , Hydrogen-Ion Concentration , Imidazolidines/isolation & purification , Imidazolidines/metabolism , Limit of DetectionABSTRACT
Enteropathogenic Escherichia coli (EPEC) expressing the Type III secretion system (TTSS) induced hemolysis of sheep blood cells. Using this assay, six structurally related compounds designated as guadinomines were isolated as inhibitors of TTSS-induced hemolysis by ion exchange column chromatography and HPLC from the culture broth of Streptomyces sp. K01-0509. Guadinomines A and B showed potent inhibition with IC50 values of 0.02 and 0.007 microg/ml, respectively, guadinomine D showed moderate activity (IC50: 8.5 microg/ml), while guadinomines C1 and C2 and guadinomic acid had no activity.
Subject(s)
Anti-Bacterial Agents/biosynthesis , Dipeptides/blood , Fermentation , Imidazolidines/blood , Streptomyces/classification , Streptomyces/metabolism , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Dipeptides/isolation & purification , Dipeptides/pharmacology , Imidazolidines/isolation & purification , Imidazolidines/pharmacologyABSTRACT
Four different types of marine natural compounds isolated from tunicates were found to inhibit human aldose reductase. They all are characterized by a heterocyclic system, and at least two phenolic groups are present in the structure. Two of the compounds tested showed an inhibitory potency 5/6-fold higher than that of the known AR inhibitor sorbinil. One notable structural feature of these active compounds is the lack of either the carboxylic acid or the spiro-hydantoin commonly present in the principal classes of currently used inhibitors.
