High-Performance Liquid Chromatographic Determination of the Stability of Sisomicin in Hydrophilic Petrolatum Ointment

For the purpose of investigating of its suitability for topical application, the stability of sisomicin incorporated in hydrophilic petrolatum was investigated under various storage conditions by high-performance liquid chromatography. Sisomicin was extracted from the oleaginous vehicle, which was kept in a liquid state by adding liquid paraffin, using pH 6.5 phosphate buffer. An appropriate retention behavior of the antibiotic is obtained on a μ Bondapak-C₁₈ column with a mobile phase of 2.0% (w/v) sodium sulfate-0.005 m sodium 1-pentanesulfate (detection at 214 nm). The degradation of sisomicin follows first-order kinetics with regard to the remaining antibiotic in aqueous solution: the apparent first-order rate constants are 2.63 xl0^-3d^-1at 5 °C and 1.70 x 10^-2d^_1 at 25 °C. When incorporated in hydrophilic petrolatum, the antibiotic is 5 to 7 times more stable than in an aqueous medium. This is due to the reduction of its surface oxidation. Accordingly, the ointment is therapeutically effective for at least 3 months when preserved under shielding from light at 5 °C.