HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ASSAY FOR THE MEASUREMENT OF THE NOVEL MICROTUBULE INHIBITOR 1069C85 IN BIOLOGICAL TISSUES AND FLUIDS

1069C85 is a novel tubulin binder developed to circumvent the resistan ce associated with the Vinca alkaloids. Cytotoxic activity has been de monstrated in vitro against a variety of tumour cell lines, including a variant of the P388 leukaemia with acquired resistance to vincristin e. A phase I clinical trial is planned and an assay suitable for precl inical and clinical pharmacokinetics has been developed. A high-perfor mance liquid chromatographic (HPLC) assay is described which allows me asurement of 1069C85 in plasma, urine, and tissue samples. The method uses reversed-phase chromatography with isocratic elution and detectio n by fluorescence at 406 nm following excitation at 340 nm. The assay is specific, sensitive (limit of sensitivity 0.25 ng/ml) and reproduci ble (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 l ife 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 p hase I clinical trial.