Sensitive isocratic high-performance liquid chromatographic determination of a novel indoloquinone cytotoxic drug (EO9) in human plasma and urine

J Chromatogr. 1993 Jun 2;615(2):309-15. doi: 10.1016/0378-4347(93)80346-6.

Abstract

A reversed-phase isocratic high-performance liquid chromatographic method is described for the simultaneous determination of EO9, 3-hydroxymethyl-5-aziridinyl-1-methyl-2-(1H-indole-4,7-dione)prop-beta- en-alpha-ol (I), and its ring-opened aziridine analogue EO5A (II), employing ultraviolet detection. Solid-phase sample extraction was used without addition of an internal standard. Plots of peak heights and areas of I and II were linear in the range 5-10,000 ng/ml. The lower limit of detection of both I and II in plasma was 2 ng/ml. The between-day variation of I was 13.9% at 5 ng/ml and lower than 6.2% for concentrations > or = 10 ng/ml. The between-day variation of II at 5 ng/ml was 13.8% and lower than 4.5% for concentrations > or = 10 ng/ml. The assay was developed to enable pharmacological guiding of a phase I study of I in solid tumour cancer patients.

MeSH terms

  • Antineoplastic Agents / analysis*
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / urine
  • Aziridines / analysis*
  • Aziridines / blood
  • Aziridines / urine
  • Chromatography, High Pressure Liquid
  • Humans
  • Indicators and Reagents
  • Indolequinones*
  • Indoles / analysis*
  • Indoles / blood
  • Indoles / urine
  • Spectrophotometry, Ultraviolet

Substances

  • Antineoplastic Agents
  • Aziridines
  • Indicators and Reagents
  • Indolequinones
  • Indoles
  • EO 5A
  • apaziquone