Summary
An HPLC method using paired-ion chromatography on RP C-18 material was developed. After sample clean up on XAD columns, mitoxantrone (Novantrone®; dihydroxyanthracenedione) in concentrations below 1 ng/ml in serum and 0.2 ng/ml in urine were measurable with a coefficient of variation <9.3% at a wavelength of 658 nm. Four metabolites were separated in urine. The major metabolite cochromatographed with the synthesized dicarboxylic acid of mitoxantrone. Within 48 hours 4.4% of the administered dose was excreted in urine as mitoxantrone, 0.5% as metabolite 1 and 0.3% as metabolite 2.
The pharmacokinetic parameters are adequately described by a three-compartment model with a terminal half-life of 214.8 hours, and a volume of distribution (ss) of 3792 litres. The total body clearance was 358 ml/min and the renal clearance was 26.2 ml/min.
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Ehninger, G., Proksch, B., Heinzel, G. et al. The pharmacokinetics and metabolism of mitoxantrone in man. Invest New Drugs 3, 109–116 (1985). https://doi.org/10.1007/BF00174157
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DOI: https://doi.org/10.1007/BF00174157