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

Stefan W. Toennes; David Schneider; Werner Pogoda; Alexander Paulke; Cora Wunder; Eef L. Theunissen; Elizabeth B. de Sousa Fernandes Perna; Johannes G. Ramaekers

doi:10.1016/j.jpba.2019.113008

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

Stefan W. Toennes^*, David Schneider, Werner Pogoda, Alexander Paulke, Cora Wunder, Eef L. Theunissen, Elizabeth B. de Sousa Fernandes Perna, Johannes G. Ramaekers

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Article number	113008
Number of pages	8
Journal	Journal of Pharmaceutical and Biomedical Analysis
Volume	179
DOIs	https://doi.org/10.1016/j.jpba.2019.113008
Publication status	Published - 3 Feb 2020

Keywords

Pharmacokinetics
Stimulants
4-Fluoroamphetamine
New psychoactive substances (NPS)
Liquid chromatography-mass spectrometry
Urine
Forensic toxicology
FLUORINE
SERUM

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10.1016/j.jpba.2019.113008

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@article{f12b6bdf5d0c4d7ea6e10537b0e71e19,

title = "Excretion of 4-fluoroamphetamine and three metabolites in urine after controlled oral ingestion",

abstract = "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.",

keywords = "Pharmacokinetics, Stimulants, 4-Fluoroamphetamine, New psychoactive substances (NPS), Liquid chromatography-mass spectrometry, Urine, Forensic toxicology, FLUORINE, SERUM",

author = "Toennes, {Stefan W.} and David Schneider and Werner Pogoda and Alexander Paulke and Cora Wunder and Theunissen, {Eef L.} and Perna, {Elizabeth B. de Sousa Fernandes} and Ramaekers, {Johannes G.}",

note = "Funding Information: Funding: this work was supported by the European Union (HOME/2014/JDRU/AG/DRUG/7082 , Predicting Risk of Emerging Drugs with In silico and Clinical Toxicology (PREDICT)). Funding Information: Funding: this work was supported by the European Union (HOME/2014/JDRU/AG/DRUG/7082, Predicting Risk of Emerging Drugs with In silico and Clinical Toxicology (PREDICT)). Publisher Copyright: {\textcopyright} 2019 Elsevier B.V.",

year = "2020",

month = feb,

day = "3",

doi = "10.1016/j.jpba.2019.113008",

language = "English",

volume = "179",

journal = "Journal of Pharmaceutical and Biomedical Analysis",

issn = "0731-7085",

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TY - JOUR

T1 - Excretion of 4-fluoroamphetamine and three metabolites in urine after controlled oral ingestion

AU - Toennes, Stefan W.

AU - Schneider, David

AU - Pogoda, Werner

AU - Paulke, Alexander

AU - Wunder, Cora

AU - Theunissen, Eef L.

AU - Perna, Elizabeth B. de Sousa Fernandes

AU - Ramaekers, Johannes G.

N1 - Funding Information: Funding: this work was supported by the European Union (HOME/2014/JDRU/AG/DRUG/7082 , Predicting Risk of Emerging Drugs with In silico and Clinical Toxicology (PREDICT)). Funding Information: Funding: this work was supported by the European Union (HOME/2014/JDRU/AG/DRUG/7082, Predicting Risk of Emerging Drugs with In silico and Clinical Toxicology (PREDICT)). Publisher Copyright: © 2019 Elsevier B.V.

PY - 2020/2/3

Y1 - 2020/2/3

N2 - 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.

AB - 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.

KW - Pharmacokinetics

KW - Stimulants

KW - 4-Fluoroamphetamine

KW - New psychoactive substances (NPS)

KW - Liquid chromatography-mass spectrometry

KW - Urine

KW - Forensic toxicology

KW - FLUORINE

KW - SERUM

U2 - 10.1016/j.jpba.2019.113008

DO - 10.1016/j.jpba.2019.113008

M3 - Article

C2 - 31785931

SN - 0731-7085

VL - 179

JO - Journal of Pharmaceutical and Biomedical Analysis

JF - Journal of Pharmaceutical and Biomedical Analysis

M1 - 113008

ER -