Simultaneous determination of dacarbazine, its photolytic degradation product, 2-azahypoxanthine, and the metabolite 5-aminoimidazole-4-carboxamide in plasma and urine by high-pressure liquid chromatography.
A high-pressure liquid chromatographic method has been developed that allows for the simultaneous analysis of dacarbazine (DTIC), 5-aminoimidazole-4-carboxamide (AIC), and 2-azahypoxanthine (2-AZA) in plasma or urine. Plasma samples were prepared by ultrafiltration, whereas urine samples were filtered and diluted for analysis. Chromatography was done with a C18 mu Bondapak column along with gradient elution of the drugs. The mobile phase consisted of 100% 0.5 M sodium acetate (pH 7.0) and 25% acetonitrile in 0.05 M sodium acetate (pH 5.5) with detection at 280 nm. Linearity was observed up to 500 micrograms/ml for DTIC and up to 53 micrograms/ml for AIC and 2-AZA. The assay methodology was reproducible, with a lower limit of detection of 5.0, 0.5, and 0.5 micrograms/ml for DTIC, AIC, and 2-AZA, respectively. Interday and intraday coefficients of variation ranged between 4 to 14% and 2 to 16%, respectively. The analytical method was applied to the analysis of plasma and urine samples resulting from the isolation perfusion chemotherapy of an extremity with 57 mg of DTIC per kg in a patient with melanoma.
D000620:Aminoimidazole Carboxamide / Q000032:analysis* / Q000097:blood / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D003606:Dacarbazine / Q000032:analysis* / Q000097:blood / Q000652:urine; D006801:Humans; D007042:Hypoxanthines / Q000032:analysis* / Q000097:blood / Q000652:urine; D007093:Imidazoles / Q000032:analysis*; D007700:Kinetics; D008545:Melanoma / Q000378:metabolism
D007042:Hypoxanthines; D007093:Imidazoles; D000620:Aminoimidazole Carboxamide; D003606:Dacarbazine; C012759:2-azahypoxanthine