EXPEDIENT LIQUID-CHROMATOGRAPHIC ASSAY FOR PACLITAXEL IN PLASMA AFTERITS ADMINISTRATION TO CANCER-PATIENTS

A rapid and expedient liquid chromatographic method for the analysis o f paclitaxel in plasma is described. Paclitaxel and the internal stand ard (IS, N-nitrosodiphenylamine) were separated on a 10-mu m particle, 8 mm x 10 cm C-18 cartridge in conjunction with a radial compression system preceded by Guard Pak with a C-18 insert. The mobile phase was a mixture of 1 mM sodium phosphate buffer (pH 5) and acetonitrile (55. 5:45.5 per volume), and the flow rate was 4.5 ml/min. The compounds we re extracted from plasma with ethyl acetate and were detected in the e ffluent spectrophotometrically at 227 nm. The recovery of paclitaxel f rom plasma at concentrations equivalent to 50, 400, and 800 mu g/L pac litaxel in plasma was 79.1, 75.2, and 74.3%, respectively, and the ret ention times of the drug and IS under these conditions were 5.26 and 6 .45 min, respectively. The relationship between the concentration and peak height ratio (drug/IS) was linear (r = 0.9938-0.9998) in the rang e of 10-1,600 mu g/L, and no interference in the assay was observed. T he intrarun coefficient of variations (CV) at 50, 250, and 800 mu g/L were 4.9, 5.4, and 4.1%, respectively, and the deviations from theoret ical accuracy at these concentrations were 1.2, 0.5, and 5.4%, respect ively. We are currently using this assay to investigate the pharmacoki netics of paclitaxel in cancer patients treated with this agent in a c ombined chemotherapy.