Excretion of 4-fluoroamphetamine and three metabolites in urine after controlled oral ingestion

•4-Fluoroamphetamine (4-FA) is obviously the main excretion product in urine.•Concentrations up to 12 h after oral ingestion are in the range of 0.7–38 mg/l.•Creatinine normalized concentrations were maximal 4 h after ingestion.•One major and one minor diastereomer of 4-fluorophenylpropanolamine was detected.•One highly conjugated ring hydroxylated 4-FA was detected. Each year, synthetic drugs are occurring in high numbers in the illicit drug market. But data on their pharmacology and toxicology are scarcely available. Therefore, a pilot study was performed to evaluate excretion of 4-fluoroamphetamine (4FA) in humans and identify metabolites in urine. Twelve subjects ingested 100 mg and five 150 mg 4-FA in a bitter lemon drink. Urine samples were scheduled at baseline and 4 times during the following 12 h and analyzed by liquid chromatography-mass spectrometry (LC-MSMS). Concentrations of 4-FA were in the range of 0.7–38 mg/l which is in accordance with the data in previously reported cases. A marked decrease of creatinine excretion in the first two samples was noted. The creatinine normalized concentrations show a maximum 4 h after ingestion in accordance with serum pharmacokinetics. Three products of two metabolic pathways were identified in very low concentrations, two diastereomers of 4-fluorophenylpropanolamine and one ring hydroxylated 4-FA that was conjugated to a large extent. The concentration-time courses paralleled those of 4-FA. The study results show the range of 4-FA concentrations to be expected in urine after oral ingestion of typical dosages and show two pathways of 4-FA metabolism.