No abstract

SUMMARYA reversed-phase high-performance liquid chromatographic method with reductive mode electrochemical detection was developed for the determination of misonidazole and desmethylmisonidazole in plasma. A thin-layer amperometric detector with glassy carbon working electrode was used to detect the nitroimidazoles at a potential of -0.60 V. The calibration curves were linear. The within-day and day-to-day coefficients of variation were below 3% for plasma misonidazole concentrations of 6-60 mg/l and l-15 mg/l for desmethylmisonidazole.Electrochemical detection limits were between 2 and 4 pg, which is about lo-20 times lower than that obtained by detection at 323 nm. Limits of quantitation of the nitroimidazoles in plasma were in the order of l-2 @g/l. Under the described conditions other nitroimidazoles and nitro compounds can also be detected with ultimate sensitivity by reductive mode electrochemical detection.

1 Oral doses of misonidazole between 0.75 and 1.3 g/m2 were administered during 3-5 days per week to 21 patients with various malignancies. 2 Mean plasma levels of misonidazole and desmethylmisonidazole at the times of radiotherapy were in the range 20-50 and 2-12 mg/l respectively. 3 Slight accumulation of misonidazole and desmethylmisonidazole in plasma was observed with a dosage interval of 24 h. 4 In patients with anticonvulsant comedication plasma elimination half-lives of misonidazole of 4.1-8.9 h were found. 5 Observed side-effects were nausea and vomiting (9%), exanthema or rashes (14%) and mild peripheral neuropathy (9%).