Determination of dissociation constants of selected cyclodextrin-benzaldehyde inclusion complexes using pulse polarography.
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Biomedical subjects
Publications and source records attributed to A M Knevel.
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5R,6R-Benzylpenicilloic acid was found to epimerize slowly in alkaline media to 5S,6R-benzylpenicilloic acid until equilibrium was established. Epimerization proceeded via the imine tautomer of penamaldic acid rather than the enamine form and was found to favor the 5S,6R-epimer at equilibrium. The conversion process was monitored using both reverse-phase high-performance liquid chromatography and NMR spectroscopy.
An ion-pair reversed-phase high-pressure liquid chromatographic technique capable of separating penicillin and its major degradation products within 8 min was developed. The influence of pH, counterion concentration, buffer concentration, and organic modifier content was studied and the observed behavior of the compounds during the chromatographic process was discussed.
Examination of the influence of the solvent of crystallization on the solid-state oxidation of dialuric acid (I) monohydrate to alloxantin (II) is reported. This reaction was investigated at low and high humidities using photomicrography, X-ray crystallography, and IR and mass spectrometry. Crystals of dialuric acid desolvated somewhat anisotropically; this behavior was consistent with crystal packing. The desolvated crystals of dialuric acid monohydrate had approximately the same crystal structure as the monohydrate and were stable in air at room temperature at low humidities. At high humidity, these crystals rehydrated and rapidly oxidized to alloxantin. These studies showed for the first time that desolvation was not a necessary prerequisite to solid-state oxidation and that solid-state oxidation reactions could be accelerated by high humidity.
During the study of the temporal changes of benzylpenicillenic acid in aqueous buffers using differential pulse polarography, penicillamine was found to be a degradation product at neutral pH. Since this result was not previously reported, the effects of pH and buffer concentration on penicillamine formation were investigated. The amount of penicillamine produced was greatest under conditions producing maximum benzylpenicillenic acid stability. Penicillamine was not obtained from benzylpenicilloic acid, the reported degradation product of benzylpenicillenic acid at neutral pH. Penicillamine also was detected in penicillin G solutions of neutral pH. Therefore, it is suggested that penicillamine found in penicillin G solutions arises from benzylpenicillenic acid degradation which, in turn, is produced from penicillin G isomerization. A pathway is proposed to show that penicillamine originates from the UV-absorbing isomer of benzylpenicillenic acid.
Degradation of penicillin in acidic media (pH 2.7) was monitored by high-pressure liquid chromatography and UV spectroscopy. The effects of temperature, buffer concentration, and ionic strength were examined. A degradation pathway is proposed, and the apparent first-order rate constant and energy of activation were calculated for each reaction. One or more degradation products containing a sulfhydryl group, a functional group often suggested as having a major role in eliciting allergic responses to penicillin therapy, were present throughout the degradation scheme.
An anion-exchange high-pressure liquid chromatographic system capable of separating penicillin G potassium from five of its degradation products was developed. The retention times were: penicillin G potassium, 17.5 min; DL-penicillamine, 4.5 min; benzylpenilloic acid, 7.0 and 8.0 min; benzylpenamaldic acid, 13.0 min; benzylpenicilloic acid, 19.5 min; and benzylpenillic acid, 22.0 min. In addition, the system permits quantification using linear calibration curves.
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