PACLITAXEL METABOLITES IN HUMAN PLASMA AND URINE - IDENTIFICATION OF 6-ALPHA-HYDROXYTAXOL, 7-EPITAXOL AND TAXOL HYDROLYSIS PRODUCTS USING LIQUID-CHROMATOGRAPHY ATMOSPHERIC-PRESSURE CHEMICAL-IONIZATION MASS-SPECTROMETRY

Reversed-phase high-performance liquid chromatography/mass spectrometr y (LC/MS), with an atmospheric-pressure chemical ionization (APCI) int erface, has been applied to the identification of metabolites and deri vatives of paclitaxel (taxol) in plasma and urine of patients treated with this new anticancer drug. Protonated molecules with substantial f ragmentation were obtained using this ionization technique. The three ion series observed are characteristic of the intact molecule, the tax ane ring, and the side chain at C13. Their analysis gives information about chemical modifications of the taxane structure at different posi tions of the molecule. Urine and plasma extracts were evaluated using the capacity to perform MS analysis directly on the entire efflueut fr om conventional LC columns. Excellent spectra were obtained with 50 pm ol of separated compounds in full scan mode. This technique allowed hi ghly sensitive identification of 6 alpha-hydroxytaxol, the major human biliary metabolite, and of 7-epitaxol in extracts of plasma and urine from patients. Taxol hydrolysis derivatives were observed for the fir st time in urine 24 hours after the end of the infusion period. Sensit ivity could be increased further using single ion monitoring (SIM) mod e, once a target derivative was identified. These results demonstrate that LC/MS with an APCI interface is useful for the characterization a nd pharmacokinetic analysis of taxoids in biological matrices.