STABILITY AND COMPATIBILITY OF MINOCYCLINE HYDROCHLORIDE AND RIFAMPIN IN INTRAVENOUS SOLUTIONS AT VARIOUS TEMPERATURES

The stability and compatibility of minocycline hydrochloride and rifampin in intravenous solutions at several temperatures were studied. Triplicate test solutions of (1) minocycline hydrochloride 0.1 mg/mL or rifampin 0.1 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection and (2) minocycline hydrochloride 0.1 mg/mL admixed with rifampin 0.1 mg/mL in 0.9% sodium chloride injection were prepared and stored at various temperatures. Samples were removed at intervals for up to seven days and stored at -70-degrees-C until analyzed. Drug concentration was measured by stability-indicating high-performance liquid chromatography. Compatibility was assessed by visual and turbidimetric examination. For the solutions containing the drugs separately, minocycline hydrochloride was stable in both diluents, with the initial concentration declining by 8% at 24-degrees-C and 2% at 4-degrees-C over seven days. Rifampin was less stable, losing 6-8% of the initial concentration in three days at 4 4-degrees-C and 5-7% in 8 hours and 13-17% in 24 hours at 24-degrees-C. There was no change in turbidity in the solutions containing either minocycline hydrochloride or rifampin. The admixture, however, was turbid after 72 hours at 37-degrees-C. Minocycline hydrochloride in the admixture was stable for seven days at 24 and 4-degrees-C but not for three days at 37-degrees-C. The concentration of rifampin decreased 20% in one day at 24-degrees-C, 8-10% in three days at 4-degrees-C, and 14% in 4 hours and 40% and in 24 hours at 37-degrees-C. When admixed in 0.9% sodium chloride injection and stored at 37-degrees-C, minocycline hydrochloride 0.1 mg/mL was stable for up to 24 hours but rifampin 0.1 mg/mL was stable for less than 4 hours.