A RAPID REVERSED-PHASE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC METHODFOR THE DETERMINATION OF DOCETAXEL (TAXOTERE(R)) IN HUMAN PLASMA USING A COLUMN-SWITCHING TECHNIQUE

A rapid, simple and sensitive isocratic high performance liquid chroma tography (HPLC) method was developed to measure the concentration of d ocetaxel in plasma samples with UV detection at 227 nm. The method use s a column switching technique with an Ultrasphere C-18 column (75 x 4 .6 mm ID, 3 mu, Altex, USA) as clean-up column and a CSC-nucleosil C-8 column (150 x 4.6 mm ID, 5 mu, CSC, Montreal, Canada) as the analytic al column. The mobile phase consisted of Phosphate buffer (30 mM, pH = 3)-acetonitrile (47:53, v/v) with the flow rates of 1.1 and 1.3 ml mi n(-1) for clean-up and analytical columns, respectively. Paclitaxel wa s used as an internal standard. The plasma samples were extracted usin g a solid phase extraction method with Ammonium acetate (30 mM, pH = 5 )-acetonitrile (50:50, v/v) as final eluent. The extraction method sho wed a recovery of 92% for docetaxel. In this system, the retention tim es of docetaxel and Paclitaxel were 7.2 and 8.5 min, respectively. The detection limit of docetaxel in plasma is 2.5 ng ml(-1). This analyti cal method has a very good reproducibility (7.2% between-day variabili ty at a concentration of 10 ng ml(-1)). It is applicable in clinical a nd pharmacokinetic studies. (C) 1998 Elsevier Science B.V. All rights reserved.