Abstract
An analytical procedure for the simultaneous determination of hetacillin and ampicillin was developed by use of iodometric titration method. The method is shown to yield accurate results in the analysis of synthetic mixtures of both antibiotics. The hydrolytic behavior of hetacillin at low initial concentration was studied over a wide pH range at 35° and μ=0.5 by the proposed analytical method, the colorimetric determination of acetone and by a thin-layer chromatography. The hydrolysis of hetacillin in the range of pH0-9.5 undergoes to form ampicillin and acetone, while that in high alkaline region above pH 9.5 was found to be relatively complex and to produce simultaneously both ampicillin and epihetacillin. The log k1-pH profile for hetacillin disappearance gave a bell-shaped curve with a maximum rate constant (k1≃2hr-1) near pH6. The activation energies for kf were evaluated to be 23.8 and 16.7 kcal/mole at pH6.60 and pH9.10, respectively. The comparative stabilities of hetacillin and ampicillin depending upon their initial concentrations were also examined at pH6.60 and pH9.10. By means of an analog computer-simulation, a proposed scheme taken into account the concentration dependency of both ampicillin hydrolysis and hetacillin-ampicillin equillibrium was found to be sufficient to interpret the experimental data. Although time for 10% loss in activity (utilization time) for hetacillin is much close to that for ampicillin at 35° because of the rapid conversion to ampicillin, relatively large temperature dependency on kf produced a remarkable prolonged effect on the utilization time for concentrated hetacillin solution at 25°.
