Bioanalysis and disposition of alpha-fluoromethylhistidine, a new histidine decarboxylase inhibitor.
A sensitive, selective, and rapid high-performance liquid chromatographic procedure was developed for the determination of alpha-fluoromethylhistidine (alpha-FMH) in human biological samples. The plasma assay required isolation of the drug using a weak cation-exchange resin prior to HPLC analysis with UV detection. The urine assay employed postcolumn derivatization with o-phthalaldehyde (without a thiol) and fluorescence detection. The extent of metabolism of alpha-FMH in humans was studied in four healthy volunteers using tritium-labeled material. No significant differences in the plasma and urine concentrations of radioactivity and unchanged drug were detected. In addition, the radiochromatograms of selected urine samples revealed a single peak with a retention time corresponding to the unchanged drug. The evidence presented suggests negligible biotransformation of alpha-FMH in humans.
D001711:Biotransformation; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D002851:Chromatography, High Pressure Liquid; D006639:Histidine / Q000031:analogs & derivatives*; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors*; D006801:Humans; D007700:Kinetics; D008762:Methylhistidines / Q000097:blood / Q000378:metabolism* / Q000652:urine; D013056:Spectrophotometry, Ultraviolet
D008762:Methylhistidines; D006639:Histidine; C028309:alpha-fluoromethylhistidine; D002262:Carboxy-Lyases; D006640:Histidine Decarboxylase