SENSITIVE ISOCRATIC HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC DETERMINATION OF A NOVEL INDOLOQUINONE CYTOTOXIC DRUG (EO9) IN HUMAN PLASMA ANDURINE

A reversed-phase isocratic high-performance liquid chromatographic met hod is described for the simultaneous determination of EO9, ethyl-2-(1 H-indole-4,7-dione)prop-beta-en-alpha-ol (I), and its ring-opened azir idine 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 greater-than-or-equal-to 10 ng/ml. The between-day variation of II at 5 ng/ml was 13.8% and lower than 4. 5% for concentrations greater-than-or-equal-to 10 ng/ml. The assay was developed to enable pharmacological guiding of a phase I study of I i n solid tumour cancer patients.