HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC PROCEDURE FOR THE QUANTITATIVE-DETERMINATION OF PACLITAXEL (TAXOL(R)) IN HUMAN PLASMA

An isocratic high-performance liquid chromatographic method has been d eveloped and validated for the quantitative determination of paclitaxe l (Taxol (R)), a novel antimitotic, anticancer agent, in human plasma. The analysis required 0.5 ml of plasma, and was accomplished by detec tion of the UV absorbance of paclitaxel at 227 nm following extraction and concentration. The method involved extraction of paclitaxel from plasma, buffered with 0.5 mi of 0.2 M ammonium acetate (pH 5.0), onto I-mi cyano Bond Elut columns. The eluent was evaporated under nitrogen and low heat, and reconstituted with the mobile phase, acetonitrile-m ethanol-water (4:1:5, v/v/v) containing 0.01 M ammonium acetate (pH 5. 0). The samples were chromatographed on a reversed-phase octyl 5 mu m column. The retention time of paclitaxel was 10 min. The validated qua ntitation range of the method was 10-1000 ng/ml (0.012-1.17 mu M) of p aclitaxel in plasma. Standard curve correlation coefficients of 0.995 or greater were obtained during validation experiments and analysis of clinical study samples. The observed recovery for paclitaxel was 83%. Epitaxol, a biologically active stereoisomer, and baccatin III, a deg radation product, were also chromatographically separated from taxol b y this assay. The method was applied to samples from a clinical study of paclitaxel in cancer patients, providing a pharmacokinetic profilin g of paclitaxel.