Changes in concentrations of free propofol by modification of the solution.

Unlabelled: Because free propofol is thought to be responsible for pain on injection, we investigated the changes in concentrations of free propofol by modifying two kinds of propofol products in a medium- and long-chain triglyceride (MCT/LCT) emulsion and in an LCT emulsion. The techniques used in this study were 1) mixing 2% lidocaine (10:1), 2) mixing 5% dextrose in acetated Ringer's solution to reduce pH (10:1), and 3) changing the temperature to 4 degrees , 20 degrees , and 36 degrees C. The propofol preparations were dialyzed for 24 h, and the receptor medium was analyzed using high-performance liquid chromatography. The concentration of free propofol in propofol MCT/LCT was significantly smaller by 30% than that in propofol LCT. Neither mixing lidocaine nor cooling reduced the concentrations of free propofol in both products, but the concentrations were reduced by a decrease in pH and by an increase in temperature. Because mixing lidocaine can induce instability in an emulsion of propofol and warming can rapidly induce microbial growth, injection of lidocaine before propofol administration is recommended to reduce the pain on injection. The concentrations of free propofol in propofol MCT/LCT were significantly smaller (by approximately 30%-45%) than those in propofol LCT during any situation in this study.

Implications: Neither mixing lidocaine nor cooling reduced the concentrations of free propofol in both products but the concentrations were reduced by a decrease in pH and by an increase in temperature. Propofol medium- and long-chain triglycerides had significantly smaller concentrations by approximately 30%-45% than those in propofol long-chain triglycerides during any situation in this study.