DIRECT LIQUID-CHROMATOGRAPHIC MICRO-MEASUREMENT OF TAMOXIFEN IN PLASMA OF CANCER-PATIENTS

We describe in this report a sensitive and direct method for the analy sis of tamoxifen (TAM) in microsamples of plasma. The drug and interna l standard (quinine bisulfate, I.S.) were separated on a 10-mu m parti cle, 10 cm x 8 mm CN cartridge in conjunction with a radial compressio n system. The mobile phase was a mixture of 0.1 M sodium acetate in 0. 001 M tetrabutylammonium phosphate solution (pH 6) and methanol (30:70 , v/v) at a flow-rate of 4 ml/min. After addition of I.S. and o-phosph oric acid in acetonitrile (0.6 M) to the plasma (30 mu l), the mixture was placed in an ultraviolet shortwave transluminator for 2 min prior to injection into the chromatograph. The compounds were detected in t he effluent fluorometrically at excitation and emission wavelengths of 258 and 378 nm, respectively. Under these conditions, no interference in the assay from any endogenous substance or other concurrently used drugs was observed and the retention times of I.S. and TAM were 4.4 a nd 10.15 min, respectively. The concentration of TAM in plasma was lin early (r > 0.9983) related to the peak height ratio (TAM/I.S.) in the range 0.01-2.0 mu g ml(-1) and C.V. at 0.075, 0.4 and 1.2 mu g ml(-1) was less than or equal to 4.96%. We are currently using this assay for monitoring TAM in plasma and investigating its pharmacokinetics in ca ncer patients receiving cytotoxic drugs in addition to TAM as a multi- drug resistance modifier.