Solubility and stability of amphotericin B in human serum.

The solubility and stability of amphotericin B in human serum in vitro was assessed using a sensitive high performance liquid chromatographic technique. The solubility of amphotericin B at concentrations ranging from 0.5 micrograms/ml to 10 micrograms/ml in human serum at pH 7.4, at 37 degrees C, and in 5% CO2 (simulated in vivo conditions) showed no significant difference compared with the solubility at 23 degrees C in room air after a 1 h incubation period. Dissolution of the colloidal suspension at a concentration of 2 micrograms/ml reached 81% in 3 min with a small increase in solubility by 60 min. Amphotericin B was very stable (less than 5% loss) in human serum at -20 degrees C for up to 14 days with only a 10% loss of drug at 6 months. In dimethylsulfoxide, however, losses at 6 months were greater than 60%. We conclude that amphotericin B solubilizes, but not completely, from a colloidal form in human serum under simulated in vivo conditions at 37 degrees C and at 23 degrees C in room air over 1 hour. Additionally, amphotericin B is stable in frozen serum for 6 months.