ANALYSIS OF ECTEINASCIDIN-743, A NEW POTENT MARINE-DERIVED ANTICANCERDRUG, IN HUMAN PLASMA BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY IN COMBINATION WITH SOLID-PHASE EXTRACTION

A reversed-phase high-performance liquid chromatographic method has be en developed and validated for the quantification of the novel antican cer drug Ecteinascidin 743 in human plasma. The sample pretreatment of the plasma samples involved a solid-phase extraction (SPE) on cyano c olumns. Propyl-p-hydroxybenzoate was added after the sample pretreatme nt to correct for variability in injection volumes. The separation was performed on a Zorbax SB-C-18 column (75x4.6 mm I.D., particle size 3 .5 mu m) with acetonitrile-25 mM phosphate buffer, pH 5.0 (70:30, v/v) as the mobile phase. The flow-rate was 1.0 ml/min and the eluent was monitored at 210 nm. The accuracies and precisions of the assay fall w ithin +/-15% for all quality control samples and within +/-20% for the lower limit of quantitation, which was 1.0 ng/ml using 500 mu l of pl asma. The overall recovery of the sample pretreatment procedure for Ec teinascidin 743 was 87.0+/-5.9%. The drug was found to be stable in hu man plasma at -30 degrees C for at least 2 months. At room temperature Ecteinascidin 743 was stable in human plasma for 5 h at most. (C) 199 8 Elsevier Science B.V. Air rights reserved.