Simultaneous determination of the new anticancer agent amidox and its metabolites in rat bile and plasma by high-performance liquid chromatography |
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| Authors: | Elisabeth Vielnascher,Darina Romanová ,Ladislav Novotný ,Thomas Szekeres,Howard L. Elfort,Therese Thalhammer,Walter Jä ger |
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| Affiliation: | aInstitute of Pharmaceutical Chemistry, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria;bDepartment of Experimental Therapy, Cancer Research Institute, Slovak Academy of Science, Spitalska 21, 812 32 Bratislava, Slovak Republic;cInstitute of Medical Chemistry University of Vienna, Währinger Strasse 10, 1090 Vienna, Austria;dMolecules for Health Inc., 3313 Gloucester Road, Richmond, VA 23227, USA;eDepartment of General and Experimental Pathology, University of Vienna, Vienna, Austria |
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| Abstract: | A new reversed-phase ion-pair high-performance liquid chromatography method was developed to study the first-pass hepatic metabolism of the anti cancer drug amidox in bile. Separation of the metabolites was achieved on a Spherisorb C18 column after liquid-liquid extraction using a linear gradient system of heptanesulfonic acid in potassium phosphate monobasic (pH 4.0) with increasing amounts of methanol (0–40%). The method was further applied to a pharmacokinetic study of amidox in rats after 200 mg kg−1 intraperitoneal administration. Using 50 μl of rat bile and 300 μl of rat plasma the limit of detection for amidox was 60 ng and 85 ng, respectively, and the assay was linear from 0.1 to 150 μg ml−1. This method appears to be sensitive enough to be used in further pharmacokinetic studies of amidox in human volunteers. |
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| Keywords: | Amidox |
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