Quantification of paclitaxel metabolites in human plasma by high-performance liquid chromatography.
A reversed-phase high-performance liquid chromatographic (HPLC) method has been validated for the quantitative determination of the three major paclitaxel metabolites (6 alpha-hydroxypaclitaxel, 3'-p-hydroxypaclitaxel, 6 alpha,3'-p-dihydroxypaclitaxel) in human plasma. The HPLC system consists of an APEX-octyl analytical column and acetonitrile-methanol-0.02 M ammonium acetate buffer pH 5 (AMW; 4:1:5, v/v/v) as the mobile phase. Detection is performed by UV absorbance measurement at 227 nm. The sample pretreatment of the plasma samples involves solid-phase extraction (SPE) on Cyano Bond Elut columns. The concentrations of the metabolic products could be determined by using the paclitaxel standard curve with a correction factor of 1.14 for 6 alpha,3'-p-dihydroxypaclitaxel. The recoveries of paclitaxel and the metabolites 6 alpha,3'-p-dihydroxypaclitaxel, 3'-p-hydroxypaclitaxel and 6 alpha-hydroxypaclitaxel in human plasma were 89, 78, 91 and 89%, respectively. The accuracy of the assay for the determination of paclitaxel and its metabolites varied between 95 and 97%, at a 50 ng/ml analyte concentration. The lower limit of quantitation was 10 ng/ml for both the parent drug and its metabolites.
Huizing
M T
MT
Department of Medical Oncology, Antoni van Leeuwenhoek Hospital/Netherlands Cancer Institute, Amsterdam.
Sparreboom
A
A
Rosing
H
H
van Tellingen
O
O
Pinedo
H M
HM
Beijnen
J H
JH
D000085:Acetates; D000097:Acetonitriles; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood*; D002021:Buffers; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000432:Methanol; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D013056:Spectrophotometry, Ultraviolet; D043823:Taxoids
D000085:Acetates; D000097:Acetonitriles; D000972:Antineoplastic Agents, Phytogenic; D002021:Buffers; D043823:Taxoids; C102050:3'-p-hydroxypaclitaxel; C086219:6-hydroxytaxol; C102049:6,3'-p-dihydroxypaclitaxel; D017239:Paclitaxel; C018824:ammonium acetate; D000432:Methanol; C032159:acetonitrile