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

J Chromatogr B Biomed Appl. 1995 Dec 15;674(2):261-8. doi: 10.1016/0378-4347(95)00308-8.

Abstract

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.

MeSH terms

  • Acetates
  • Acetonitriles
  • Antineoplastic Agents, Phytogenic / blood*
  • Buffers
  • Chromatography, High Pressure Liquid / methods*
  • Chromatography, High Pressure Liquid / statistics & numerical data
  • Humans
  • Hydrogen-Ion Concentration
  • Methanol
  • Paclitaxel / analogs & derivatives*
  • Paclitaxel / blood*
  • Paclitaxel / pharmacokinetics
  • Spectrophotometry, Ultraviolet
  • Taxoids*

Substances

  • Acetates
  • Acetonitriles
  • Antineoplastic Agents, Phytogenic
  • Buffers
  • Taxoids
  • 3'-p-hydroxypaclitaxel
  • 6-hydroxytaxol
  • 6,3'-p-dihydroxypaclitaxel
  • Paclitaxel
  • ammonium acetate
  • Methanol
  • acetonitrile