pH-dependent effect of magnesium sulfate on the stability of penicillin G potassium solution

The effect of magnesium sulfate on the stability of penicillin G potassium solutions (0.5 mg/mL) was investigated using a stability-indicating high-performance liquid chromatography method. The penicillin G potassium powder buffered with and without citrate was used. Twelve aqueous duplicate penicillin solutions with various concentrations of magnesium sulfate and with or without buffers were prepared and stored at room temperature. Data on clarity, pH values, and HPLC assay results were determined at intervals during the 10-day storage period. The results indicated that the presence of high concentrations of magnesium sulfate in unbuffered penicillin solutions can cause large pH changes and the degradation of penicillin. However, the effect of magnesium sulfate on the stability of penicillin G potassium was negligible in the buffered solutions. Solutions with a constant pH value of 5.6 prepared using 0.1 M acetate buffer with and without magnesium sulfate showed similar apparent first-order degradation after the 10-day storage period at 24 degrees C. During decomposition, the pH values of the unbuffered solutions decreased for three days and then started increasing in most solutions. The degradation of penicillin G potassium by magnesium sulfate in aqueous solutions resulted from decreases in pH values of the solutions.