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 spectrometry (LC/MS), with an atmospheric-pressure chemical ionization (APCI) interface, has been applied to the identification of metabolites and derivatives of paclitaxel (taxol) in plasma and urine of patients treated with this new anticancer drug. Protonated molecules with substantial fragmentation were obtained using this ionization technique. The three ion series observed are characteristic of the intact molecule, the taxane ring, and the side chain at C13. Their analysis gives information about chemical modifications of the taxane structure at different positions of the molecule. Urine and plasma extracts were evaluated using the capacity to perform MS analysis directly on the entire effluent from conventional LC columns. Excellent spectra were obtained with 50 pmol of separated compounds in full scan mode. This technique allowed highly 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 first time in urine 24 hours after the end of the infusion period. Sensitivity could be increased further using single ion monitoring (SIM) mode, once a target derivative was identified. These results demonstrate that LC/MS with an APCI interface is useful for the characterization and pharmacokinetic analysis of taxoids in biological matrices.
Royer
I
I
CNRS Laboratoire de Pharmacologie et de Toxicologie Fondamentales, Toulouse, France.
Alvinerie
P
P
Armand
J P
JP
Ho
L K
LK
Wright
M
M
Monsarrat
B
B
D001646:Bile / Q000737:chemistry / Q000378:metabolism; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D013058:Mass Spectrometry; D017239:Paclitaxel / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
D017239:Paclitaxel