Quantitative Determination of Related Substances in Propofol by Supercritical Fluid (CO2) Chromatography

An environmentally friendly, simple and rapid supercritical fluid chromatography (SFC) method was established and validated for the simultaneous determination of ten related substances in propofol bulk drug. The separation was achieved on a Zorbax-silica column at 40 & DEG;C with a mobile phase consisting of supercritical carbon dioxide (CO2) and heptane containing 10% isopropanol (98 : 2, v/v) in 11 min. Satisfactory resolution and peak shapes for propofol and ten related substances were obtained after optimizing the chromatography system. The ten related substances could be accurately quantified in the 0.03-0.63 & mu;g/mL concentration range with correlation coefficients (r(2)) ranging from 0.9991 to 0.9998 and recoveries ranging from 92.0 to 113.2%. Furthermore, five stress tests demonstrated that propofol bulk drug degradation occurred under the condition of heat, oxidative degradation, acid and base hydrolysis. Results of orthogonality to our prior GC-MS/MS method suggested this SFC method was time-saving and alternative for propofol quality control.