Sulfite supported lipid peroxidation in propofol emulsions

Abstract

Background: Sodium metabisulfite is added to a commercial propofol emulsion as an antimicrobial agent. The sulfite ion (SO3-2) is capable of undergoing a number of reactions, including autooxidation and the promotion of lipid peroxidation. This study evaluated sulfite reactivity in propofol emulsions by determining thiobarbituric acid reacting substances (TBARS), sulfite depletion, and emulsion pH in emulsions containing sulfite or EDTA. Methods: Commercial EDTA and sulfite propofol emulsions were compared, and 10% soybean oil emulsion containing various additives were evaluated for TBARS, sulfite, and pH. TBARS were analyzed with a modified thiobarbituric acid method. Sulfite was analyzed by the reaction of sulfite with 5,5′-dithiobis(2-nitrobenzoic acid). pH was measured by glass electrode methodology. Results: Thiobarbituric acid reacting substances were detectable in commercial sulfite propofol emulsions in concentrations ranging from 0.02 to 0.22 μg/ml based on malondialdehyde. No TBARS were detected in EDTA propofol emulsions. Incubation (37°C, up to 6 h) of sulfite propofol emulsions in air resulted in further increases in TBARS (35-160%). No increases occurred in incubated EDTA propofol emulsions. Metabisulfite (0.25 mg/ml) alone added to 10% soybean oil resulted in large increases in TBARS that were inhibited in part by propofol (10 mg/ml) and completely by ascorbic acid (0.05 mg/ml). Soybean oil emulsion pH declined rapidly on the addition of metabisulfite (0.25 mg/ml). The addition of propofol (10 mg/ml) partially inhibited the decline in pH and ascorbic acid (0.05 mg/ml) completely inhibited it. Conclusion: These results show that sulfite supports the peroxidation of lipids in soybean oil emulsions and propofol functions to partially inhibit these processes.