Paul J. Niebergall

Aspects of the epimerization of certain tetracycline derivatives

The epimerization of several tetracycline derivatives was examined at several pH values using varying conditions of temperature and buffer strength. Rate coefficients for the epimerization of tetracycline and demethylchlortetracycline are reported and factors associated with the epimerization of chlortetracycline and oxytetracycline are discussed. Under the conditions used calcium had no effect on the rate of epimerization and copper promoted degradation other than epimerization.

Metal binding tendencies of various antibiotics

A method to determine the presence of metal‐drug complexes in dilute solutions is described. Using this method cycloserine was found to complex with cupric, nickelous, zinc and cobalt ions; streptomycin and novobiocin complexed with cupric ions; erythromycin complexed with cobalt ions, and chloramphenicol exhibited no metal binding tendencies. Various penicillins were found to interact with zinc and cupric ions. Preliminary investigations suggest that cupric ions, rather than simply complexing with penicillin as suggested by previous workers, promote the degradation of penicillin to penicilloic acid. Evidence is presented to confirm the presence of penicilloic acid in reaction mixtures initially containing penicillin G or V and cupric ions, and to establish that the reaction follows second order kinetics and ceases when all available cupric ion has been consumed. Good correlation was noted for these results and previous work which showed the effects of metal ions on the antibacterial properties of penicillin.

Complexation of penicillins and penicilloic acids by cupric ion

A kinetic method was developed to study the interactions between cupric ion and penicillins G and V. Complexation was found to occur with the intact penicillins, followed by rapid hydrolysis of the complex into the corresponding penicilloic acid‐cupric ion complex. The logarithmic stability constants for the interaction between cupric ion and penicillins G and V were found to be 2·61 and 2·24, respectively. In addition, the method of continuous variation was used to determine the logarithmic stability constants for the cupric ion‐penicilloic acid complexes. These were found to be 4·20 and 4·50, for penicilloic V and G acids respectively.

Gas chromatographic analysis of theophylline in human serum.

Abstract A method is presented for the analysis of theophylline in human serum. The method is specific with no interference from theophylline metabolites, ephedrine, hydrocortisone, or caffeine and their metabolites. It is sensitive to approximately 1 μg/ml and analyses over the range of 5–11 μg/ml were found to have an average relative error of 7.5%.

Mathematics of three-phase in vitro absorption models

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