Role of lipid in sulfite-dependent propofol dimerization.
BACKGROUND
During long-term intravenous infusions, sulfite in sulfite-containing propofol emulsions can cause the peroxidation of lipid and dimerization of propofol. This study evaluated the role of lipid in sulfite-dependent propofol dimerization by determining the effects of individual fatty acids in soybean oil emulsion and peroxidized lipids in a model system.


METHODS
Individual fatty acids, stearic (18:0), oleic (18:1), linoleic (18:2), linolenic (18:3), and arachidonic (20:4), were added to sulfite-containing propofol emulsion and incubated for 90 min at 37 degrees C. Model systems containing soybean oil (100 microl), water (900 microl), propofol (10 mg/ml), and sulfite (0.25 mg/ml) composed of oils with different peroxide values were allowed to react for 60 min at room temperature. After the reactions, propofol dimer and propofol dimer quinone were analyzed by reversed-phase high-pressure liquid chromatography.


RESULTS
Propofol did not dimerize when added to aqueous sulfite unless soybean oil was also included. The addition of the polyunsaturated fatty acids (linoleic, linolenic, arachidonic) to sulfite-containing propofol emulsion resulted in large increases of propofol dimerization compared with stearic or oleic acid. Using biphasic mixtures of soybean oil and aqueous sulfite, propofol dimerization increased with increasing peroxide content of the oil. In propofol emulsion, lipoxidase and ferrous iron in the absence of sulfite also caused the dimerization of propofol.


CONCLUSIONS
These results show that lipid can play a significant role in sulfite-dependent propofol dimerization. The relation of dimerization to polyunsaturated fatty acid and soybean oil peroxide content suggests that sulfite reacts with unsaturated lipid or peroxide-modified lipid to facilitate propofol dimerization.
Baker
Max T
MT
Department of Anesthesia, The University of Iowa, 200 Hawkins Drive, Iowa City, Iowa 52242, USA. max-baker@uiowa.edu
Gregerson
Marc S
MS
Naguib
Mohamed
M
D019281:Dimerization; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000502:physiology; D008055:Lipids / Q000737:chemistry* / Q000502:physiology*; D015742:Propofol / Q000737:chemistry*; D013024:Soybean Oil / Q000737:chemistry; D013447:Sulfites / Q000737:chemistry*
D005231:Fatty Acids, Unsaturated; D008055:Lipids; D013447:Sulfites; D013024:Soybean Oil; D015742:Propofol