Studies on the metabolism and toxicological detection of the amphetamine-like anorectic fenproporex in human urine by gas chromatography-mass spectrometry and fluorescence polarization immunoassay.
Studies on the metabolism and the toxicological analysis of fenproporex (R,S-3-[(1-phenyl-2-propyl)-amino]-propionitrile, FP) using GC-MS and fluorescence polarization immunoassay are described. The metabolites were identified in urine samples of volunteers by GC-MS after cleavage of conjugates, extraction and acetylation. Besides unchanged FP, fourteen metabolites, including amphetamine, could be identified. Two partially overlapping metabolic pathways could be postulated: ring degradation by one- and two-fold aromatic hydroxylation followed by methylation and side chain degradation by N-dealkylation to amphetamine (AM). A minor pathway leads via beta-hydroxylation of AM to norephedrine. For GC-MS detection, the systematic toxicological analysis procedure including acid hydrolysis, extraction at pH 8-9 and acetylation was suitable (detection limits 50 ng/ml for FP and 100 ng/ml for AM). Excretion studies showed, that only AM but neither FP nor its specific metabolites were detectable 30-60 h after ingestion of 20 mg of FP. Therefore, misinterpretation can occur. The Abbott TDx FPIA amphetamine/methamphetamine II gave positive results up to 58 h. All the positive immunoassay results could be confirmed by the described GC-MS procedure.
Kraemer
T
T
Department of Toxicology, Institute of Pharmacology and Toxicology, University of Saarland, Homburg (Saar), Germany. pttkra@med-rz.uni-sb.de
Theis
G A
GA
Weber
A A
AA
Maurer
H H
HH
D000107:Acetylation; D000661:Amphetamine / Q000652:urine; D000662:Amphetamines / Q000378:metabolism / Q000652:urine*; D001067:Appetite Depressants; D016231:Fluorescence Polarization Immunoassay; D005554:Forensic Medicine; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D006900:Hydroxylation; D008745:Methylation; D012680:Sensitivity and Specificity; D014116:Toxicology
D000662:Amphetamines; D001067:Appetite Depressants; D000661:Amphetamine; C026013:fenproporex