Quantification of paclitaxel metabolites in human plasma by high-performance liquid chromatography

被引:66
作者
Huizing, MT
Sparreboom, A
Rosing, H
vanTellingen, O
Pinedo, HM
Beijnen, JH
机构
[1] NETHERLANDS CANC INST,ANTONI VAN LEEUWENHOEK HOSP,DEPT MED ONCOL,1066 CX AMSTERDAM,NETHERLANDS
[2] SLOTERVAART HOSP,DEPT PHARM,1066 EC AMSTERDAM,NETHERLANDS
[3] NETHERLANDS CANC INST,ANTONI VAN LEEUWENHOEK HOSP,DEPT CLIN CHEM,1066 CX AMSTERDAM,NETHERLANDS
[4] FREE UNIV AMSTERDAM HOSP,DEPT MED ONCOL,1007 MB AMSTERDAM,NETHERLANDS
来源
JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS | 1995年 / 674卷 / 02期
关键词
D O I
10.1016/0378-4347(95)00308-8
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:261 / 268
页数:8
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