Study of the biotransformation of a potential benzo[ c]fluorene antineoplastic using high-performance liquid chromatography with high-speed-scanning ultraviolet detection

• Published in: Journal of chromatography. B, Biomedical applications Vol. 681; no. 1; pp. 143 - 151
• Main Authors: Nobilis, Milan, Anzenbacher, Pavel, Pastera, Jiří, Svoboda, Zbyněk, Hrubý, Kamil, Květina, Jaroslav, Ubik, Karel, Trejtnar, František
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 31.05.1996
• Subjects: Animals; Antineoplastic Agents - analysis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; Benfluron; Bile - chemistry; Biotransformation; Carcinogens - chemistry; Cells, Cultured; Chromatography, High Pressure Liquid; Fluorenes - analysis; Fluorenes - chemistry; Fluorenes - pharmacokinetics; Hepatocytes; In Vitro Techniques; Liver - cytology; Liver - metabolism; Liver, perfused; Male; Perfusion; Rats; Rats, Wistar; Spectrophotometry, Ultraviolet; Ultraviolet detection, high-speed scanning; Liver, perfused; Benfluron; Hepatocytes; Ultraviolet detection, high-speed scanning
• ISSN: 0378-4347; 1572-6495
• DOI: 10.1016/0378-4347(95)00523-4

As the sum of benfluron metabolites found was only a par of the total amount applied, a search for undiscovered metabolites was undertaken in the extracts from isolated rat hepatocytes and in the bile and perfusate in the experiments with an isolated perfused rat liver. To identify the metabolites, high-performance liquid chromatography with UV spectral analysis was used, as benfluron derivatives exhibit characteristic absorption spectra. Administration of known metabolites to experimental animals and selective induction of certain metabolic pathways led to the finding of new metabolites and of the respective conjugates. Fast atom bombardment-mass spectrometry analysis was used to identify the newly found metabolites and conjugates.