HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY TANDEM MASS-SPECTROMETRY PROCEDURE WITH AUTOMATED SOLID-PHASE EXTRACTION SAMPLE PREPARATION FOR THE QUANTITATIVE-DETERMINATION OF PACLITAXEL (TAXOL(R)) IN HUMAN PLASMA

A sensitive, specific, accurate and reproducible analytical method was developed and validated for the quantitation of the anticancer agent paclitaxel in human plasma, This procedure is based on high performanc e liquid chromatography/ion spray - tandem mass spectrometry. This met hodology is highly specific because a MS/MS technique (multiple reacta nt-ion monitoring, MRM) was used for both paclitaxel and its internal standard, The use of a fully automated solid phase extraction procedur e, using a CN Sep-pak cartridge, to improve the detection limit and qu antification limit of paclitaxel in human plasma samples, was evaluate d, The method involves the addition of methyl-paclitaxel as internal s tandard (I.S.). The retention times of paclitaxel and the I.S. were 2. 8 and 4.0 min., respectively, The assay was linear over the range 5 to 500 ng/mL, with a quantification limit of 5 ng/mL having a coefficien t of variation (C.V.) <10%. Standard calibration curves, performed on three different days, had correlation coefficients always greater than 0.998, The intra and inter-day precision were within 12%, and accurac y was included in the range 102-110%. Paclitaxel recovery assessed at 15,250 and 500 ng/mL, was determined to be greater than 85%. The assay is applicable to clinical pharmacokinetic studies. (C) 1998 John Wile y & Sons, Ltd.