High-performance liquid chromatographic assay of fenflumizole and its demethyl metabolites in biological samples. 1987

C Midskov

This paper describes sensitive, selective and precise methods for the assay of fenflumizole and its chromatographically verified demethyl and didemethyl metabolites in whole blood, isolated red blood cells, plasma, saliva, urine and tissue (skin and fat) from human subjects. Also conjugates of the two metabolites with glucuronic acid and sulphate were assayable. The compounds were quantitated by means of reversed-phase liquid chromatography after diethyl ether extraction, followed by fluorescence and/or electrochemical detection. The assay using fluorescence detection is quantitative down to ca. 150 pg/ml; with electrochemistry this limit was ca. 600 pg/ml and included the demethyl metabolites only. Proteinaceous materials show an extraction yield of 70-75%, whereas analytes in sample materials without proteins show yields of better than 95%. The precision at concentration levels of ca. 50 ng/ml for the parent compound and ca. 5 ng/ml for the metabolites is at most 6% (relative standard deviation) with both detection modes. The analytical procedures developed were applied after both single and repetitive administration of fenflumizole. The administration of 14C-labelled fenflumizole in the single-dose study revealed the presence in plasma and urine of as yet unknown metabolites. The in vivo retention time of 14C activity was substantially greater in the blood cells than in plasma. Measurements of 14C activity in excreta demonstrated that excretion via the faeces is the preferred route.

UI MeSH Term Description Entries
D007093 Imidazoles Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D003640 Dealkylation The removing of alkyl groups from a compound. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Dealkylations
D004912 Erythrocytes Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN. Blood Cells, Red,Blood Corpuscles, Red,Red Blood Cells,Red Blood Corpuscles,Blood Cell, Red,Blood Corpuscle, Red,Erythrocyte,Red Blood Cell,Red Blood Corpuscle
D005243 Feces Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000894 Anti-Inflammatory Agents, Non-Steroidal Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. Analgesics, Anti-Inflammatory,Aspirin-Like Agent,Aspirin-Like Agents,NSAID,Non-Steroidal Anti-Inflammatory Agent,Non-Steroidal Anti-Inflammatory Agents,Nonsteroidal Anti-Inflammatory Agent,Anti Inflammatory Agents, Nonsteroidal,Antiinflammatory Agents, Non Steroidal,Antiinflammatory Agents, Nonsteroidal,NSAIDs,Nonsteroidal Anti-Inflammatory Agents,Agent, Aspirin-Like,Agent, Non-Steroidal Anti-Inflammatory,Agent, Nonsteroidal Anti-Inflammatory,Anti-Inflammatory Agent, Non-Steroidal,Anti-Inflammatory Agent, Nonsteroidal,Anti-Inflammatory Analgesics,Aspirin Like Agent,Aspirin Like Agents,Non Steroidal Anti Inflammatory Agent,Non Steroidal Anti Inflammatory Agents,Nonsteroidal Anti Inflammatory Agent,Nonsteroidal Anti Inflammatory Agents,Nonsteroidal Antiinflammatory Agents
D012463 Saliva The clear, viscous fluid secreted by the SALIVARY GLANDS and mucous glands of the mouth. It contains MUCINS, water, organic salts, and ptylin. Salivas

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