title: Amphetamine concentrations in human urine following single-dose administration of the calcium antagonist prenylamine-studies using fluorescence polarization immunoassay (FPIA) and GC-MS.
abstract: Prenylamine (R,S-N-(3,3-diphenylpropyl-methyl-2-phenethylamine), a World Health Organization class V calcium antagonist, is known to be metabolized to amphetamine. In this study, amphetamine concentrations after a single-dose administration of prenylamine were determined to check if they reached values that could be of analytical and/or pharmacological importance in clinical and forensic toxicology. Enantiomeric composition of amphetamine was also studied. Five volunteers received a single 120-mg oral dose of prenylamine. Urine samples were analyzed using the Abbott TDx immunoassay Amphetamine/Methamphetamine II and using our routine systematic toxicological analysis (STA) gas chromatography-mass spectrometry (GC-MS) procedure. For quantitation purposes, GC-MS was used in the selected-ion monitoring (SIM) mode (ions m/z 118, 122, 240, 244) after solid-phase extraction (Isolute Confirm HCX) and derivatization (heptafluorobutyric anhydride). Amphetamine-d5 was used as internal standard (IS). Chiral separation of the heptafluorobutyrated amphetamine enantiomers was achieved using an Astec Chiraldex G-PN column. The TDx results showed a great variability for the different volunteers. A urine sample of one volunteer showed results as high as 3200 ng/mL, whereas the urine samples of another volunteer never gave results greater than the TDx detection limit (100 ng/mL). Using the STA procedure, the presence of amphetamine could be confirmed in all urine samples with TDx results greater than the cutoff value (300 ng/mL). Using the GC-MS SIM method, amphetamine concentrations up to 1280 ng/mL were determined. Chiral analysis revealed that both enantiomers of amphetamine were present in the samples with a surplus of the S(+)-enantiomer in the early phase of excretion. Forensic implications are discussed.
authors.affiliation: Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, University of Saarland, D-66421 Homburg (Saar), Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kraemer
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Roditis
authors.forename: Frank T
authors.initials: FT
authors.lastname: Peters
authors.forename: Hans H
authors.initials: HH
authors.lastname: Maurer
mesh_terms: D000661:Amphetamine / Q000652:urine*; D002121:Calcium Channel Blockers / Q000378:metabolism* / Q000493:pharmacokinetics; D000697:Central Nervous System Stimulants / Q000652:urine*; D016231:Fluorescence Polarization Immunoassay; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D011299:Prenylamine / Q000378:metabolism* / Q000493:pharmacokinetics; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; D000697:Central Nervous System Stimulants; D000661:Amphetamine; D011299:Prenylamine