High-performance liquid chromatographic assay for the measurement of the novel microtubule inhibitor 1069C85 in biological tissues and fluids

J Chromatogr. 1993 Dec 22;622(2):243-8. doi: 10.1016/0378-4347(93)80272-6.

Abstract

1069C85 is a novel tubulin binder developed to circumvent the resistance associated with the Vinca alkaloids. Cytotoxic activity has been demonstrated in vitro against a variety of tumour cell lines, including a variant of the P388 leukaemia with acquired resistance to vincristine. A phase I clinical trial is planned and an assay suitable for preclinical and clinical pharmacokinetics has been developed. A high-performance liquid chromatographic (HPLC) assay is described which allows measurement of 1069C85 in plasma, urine, and tissue samples. The method uses reversed-phase chromatography with isocratic elution and detection by fluorescence at 406 nm following excitation at 340 nm. The assay is specific, sensitive (limit of sensitivity 0.25 ng/ml) and reproducible (coefficient of variation < 5%). The method has been used to study the pharmacokinetics of 1069C85 in Balb C mice following a single oral dose of 1 mg/kg. The maximum plasma concentration was reached 15 min after administration and subsequent elimination was slow with a half life of 6.5 +/- 2.2 h. The drug remained detectable in plasma, at 1 +/- 0.5 ng/ml, 24 h after this dose. This assay will be used to determine the pharmacokinetic profile of 1069C85 in mice and in a forthcoming phase I clinical trial.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Availability
  • Carbamates / analysis*
  • Carbamates / chemistry
  • Carbamates / pharmacokinetics
  • Chromatography, High Pressure Liquid
  • Female
  • Half-Life
  • Humans
  • Intestinal Absorption
  • Mice
  • Mice, Inbred BALB C
  • Microtubules / drug effects
  • Microtubules / metabolism*
  • Pyridazines / analysis*
  • Pyridazines / chemistry
  • Pyridazines / pharmacokinetics
  • Solubility
  • Solvents
  • Spectrometry, Fluorescence

Substances

  • BW 1069C85
  • Carbamates
  • Pyridazines
  • Solvents