HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ASSAY FOR THE DETERMINATION OF THE NOVEL PODOPHYLLOTOXIN DERIVATIVE DIMETHYLAMINOETOPOSIDE (NK611) IN HUMAN PLASMA

A simple, rapid and reproducible plasma assay for the determination of the novel epipodophyllotoxin derivative, dimethylaminoetoposide (NK61 1, I) and its N-demethyl metabolite (II) is reported. The method invol ves solid-phase extraction using an isolute C18 cartridge and HPLC sep aration on a reduced-activity C18 column (8 cm long) with a mobile pha se of acetonitrile-water-0.1 M phosphoric acid (23:76:1, v/v/v); peaks are detected at 205 nm. The intra- and inter-day precision and accura cy are within 5 and 4% for I and II, respectively. The sensitivity is 20 ng/ml for both I and II. The assay is applicable to clinical pharma cokinetic studies. In one cancer patient who received both an oral and an intravenous dose of 10 mg of I the bioavailability was 82% and the clearance 20.8 ml/min.