Simultaneous determination of taxol and its metabolites in microsomal samples by a simple thin-layer chromatography radioactivity assay--inhibitory effect of NK-104, a new inhibitor of HMG-CoA reductase

J Chromatogr B Biomed Sci Appl. 2001 Jun 5;757(1):143-50. doi: 10.1016/s0378-4347(01)00141-4.

Abstract

The inhibitory effect of NK-104, a potent inhibitor of HMG-CoA reductase, on taxol metabolism was examined using radio-TLC. This method is described for in vitro measurement of taxol metabolites as an alternative to the commonly used HPLC assay. After incubation of 14C-taxol with human liver microsomes, the supernatants were developed using a solvent system consisting of toluene-acetone-formic acid (60:39:1, v/v) and quantified with a bioimaging analyzer. The described method provides a valuable tool for the simultaneous determination of unchanged taxol and its major metabolites. There was no inhibitory effect of NK-104 on CYP-mediated metabolism of taxol in human liver microsomes.

MeSH terms

  • Antineoplastic Agents, Phytogenic / antagonists & inhibitors
  • Antineoplastic Agents, Phytogenic / metabolism
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Chromatography, Thin Layer / methods*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Microsomes, Liver / metabolism
  • Paclitaxel / antagonists & inhibitors
  • Paclitaxel / metabolism
  • Paclitaxel / pharmacokinetics*
  • Quinolines / pharmacology*
  • Radiometry / methods*
  • Reproducibility of Results

Substances

  • Antineoplastic Agents, Phytogenic
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Quinolines
  • pitavastatin
  • Paclitaxel