MICRODETERMINATION OF PROPOFOL IN PLASMA BY A RAPID AND SENSITIVE LIQUID-CHROMATOGRAPHIC METHOD

A direct and sensitive liquid chromatographic method for the determina tion of propofol in 50 mu l of plasma is described. The separation of the drug and internal standard (methyldopa) was achieved using a 4 mu m particle size C-18 cartridge (10 cm x 8 mm i.d.) in conjunction with a radial compression system and a C-18 precolumn module. The mobile p hase consisted of 0.01 M sodium acetate solution (adjusted to pH 3 wit h acetic acid)-acetonitrile-methanol (37:47.25:15.75, v/v/v) at a flow rate of 2 ml min(-1). The compounds were detected in the effluent spe ctrofluorimetrically with excitation and emission wavelengths of 276 a nd 310 nm, respectively. After the internal standard had been added, t he sample was diluted with 50 mu l of hydrochloric acid and centrifuge d prior to injection into the chromatograph, The peaks of both propofo l and internal standard under these conditions were sharp and symmetri cal, and the retention times were 8.2 and 5.15 min, respectively. The peak-height ratio (drug/internal standard) varied linearly (r > 0.9959 ) with concentration in the ranges 0.002-0.1 and 0.1-10 mu g ml(-1) an d the relative standard deviation was consistently < 5.6%. There was n o interference in the assay from the endogenous substance or other con comitantly used drug. This method is currently being used for monitori ng propofol in intensive care patients and investigating its pharmacok inetics.