Differences of propofol concentrations in mammalian whole blood and in corresponding plasma samples analyzed by high performance liquid chromatography.

Background: In preparation for a study of the pharmacokinetics and elimination of propofol, a frequently used intravenous narcotic, we sought for a simple but accurate method for determining the drug in biological fluids from various mammalian species.

Materials And Methods: We established an isocratic high performance liquid chromatography (HPLC) assay with fluorimetric detection for quantification of propofol, studied the analytical characteristics of the method, and measured the narcotic in heparinized whole blood and corresponding plasma samples drawn from 5 subjects each of humans, pigs, sheep and goats prior to and after 10 minutes of constant infusion of propofol.

Results: Following protein precipitation with methanol, propofol was quantified in the alcoholic phase. With 30 microl extract, lower limits of detection and quantification of propofol were 2 and 10 microg I(-1), the measurable range extended to 8000 microg I(-1). Intra- and inter-assay CVs tested at propofol concentrations between 40 and 3000 microg I(-1) were < 3% and < 8%, respectively. Propofol levels ranged from 900 to 10,000 microg I(-1) after 10 minutes of drug infusion; among the animals treated with identical doses, pigs exhibited the highest and sheep the lowest circulating propofol concentrations.

Conclusions: Analysis of propofol by the HPLC method described is highly practicable, sensitive and specific. Propofol concentrations measured in heparinized blood and corresponding plasma samples differ slightly; in addition to inter-individual variations, species-specific differences in the drug's disposition between plasma and blood cells were observed.