Analytically Confirmed Intoxication by 4-Fluoromethylphenidate, an Analog of Methylphenidate

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Abstract

4-Fluoromethylphenidate (4F-MPH) is an halogenated derivative of methylphenidate (MPH), a re-uptake inhibitor for dopamine and norepinephrine used for the treatment of attention deficit hyperactivity disorders. In the last few years, several compounds structurally related to MPH have been marked as new psychoactive substances (NPS) with stimulating and euphoric effects similar to the parent drug, but with more dopaminergic activity. This report represents the first case of an analytically confirmed non-fatal intoxication by 4F-MPH. A 26-year-old female was admitted to the emergency department with neuropsychiatric and cardiologic symptoms that lasted for a week, during which she sniffed a powder named 4F-MPH acquired as entactogen on the Internet. The patient required sedation with intravenous diazepam and was discharged two days later with a prescription of promazine and quetiapine. The seized product was analytically characterized by gas chromatography-mass spectrometry, liquid chromatography high-resolution mass spectrometry and nuclear magnetic resonance. These analyses confirmed the composition of the product as a 4F-MPH diastereomeric (±)-threo and (±)-erythro mixture, with a large preponderance of the active (±)-threo isomer. A minimal validation, intended for rare analytes, was performed for the quantification of 4F-MPH in the biological samples by liquid chromatography-tandem mass spectrometry. Accuracy (bias) and precision were within ±15% for both blood and urine. The blood and urine concentration of (±)-threo 4F-MPH were 32 ng/mL and 827 ng/mL, respectively. Analyses for classic drugs (opiates, methadone, cocaine, cannabis metabolites, amphetamines, ecstasy and LSD), ethanol, qualitative full screen by gas chromatography-mass spectrometry and targeted analysis for 50 NPS by liquid chromatography-tandem mass spectrometry tested negative; comorbidities were excluded, too. Based on these data, it can be assumed that the clinical manifestations were due to 4F-MPH only.

Original languageEnglish
JournalJournal of Analytical Toxicology
Volume43
Issue number5
DOIs
Publication statusPublished - Jun 1 2019

Fingerprint

Methylphenidate
Liquid Chromatography
Mass spectrometry
mass spectrometry
Tandem Mass Spectrometry
Liquid chromatography
Gas Chromatography-Mass Spectrometry
Opiate Alkaloids
liquid chromatography
Promazine
Dopamine Uptake Inhibitors
Urine
Amphetamines
Lysergic Acid Diethylamide
Gas chromatography
urine
Methadone
Cannabis
Attention Deficit Disorder with Hyperactivity
Diazepam

ASJC Scopus subject areas

  • Analytical Chemistry
  • Environmental Chemistry
  • Toxicology
  • Health, Toxicology and Mutagenesis
  • Chemical Health and Safety

Cite this

@article{923c34409e5040b7b211628585b259e7,
title = "Analytically Confirmed Intoxication by 4-Fluoromethylphenidate, an Analog of Methylphenidate",
abstract = "4-Fluoromethylphenidate (4F-MPH) is an halogenated derivative of methylphenidate (MPH), a re-uptake inhibitor for dopamine and norepinephrine used for the treatment of attention deficit hyperactivity disorders. In the last few years, several compounds structurally related to MPH have been marked as new psychoactive substances (NPS) with stimulating and euphoric effects similar to the parent drug, but with more dopaminergic activity. This report represents the first case of an analytically confirmed non-fatal intoxication by 4F-MPH. A 26-year-old female was admitted to the emergency department with neuropsychiatric and cardiologic symptoms that lasted for a week, during which she sniffed a powder named 4F-MPH acquired as entactogen on the Internet. The patient required sedation with intravenous diazepam and was discharged two days later with a prescription of promazine and quetiapine. The seized product was analytically characterized by gas chromatography-mass spectrometry, liquid chromatography high-resolution mass spectrometry and nuclear magnetic resonance. These analyses confirmed the composition of the product as a 4F-MPH diastereomeric (±)-threo and (±)-erythro mixture, with a large preponderance of the active (±)-threo isomer. A minimal validation, intended for rare analytes, was performed for the quantification of 4F-MPH in the biological samples by liquid chromatography-tandem mass spectrometry. Accuracy (bias) and precision were within ±15{\%} for both blood and urine. The blood and urine concentration of (±)-threo 4F-MPH were 32 ng/mL and 827 ng/mL, respectively. Analyses for classic drugs (opiates, methadone, cocaine, cannabis metabolites, amphetamines, ecstasy and LSD), ethanol, qualitative full screen by gas chromatography-mass spectrometry and targeted analysis for 50 NPS by liquid chromatography-tandem mass spectrometry tested negative; comorbidities were excluded, too. Based on these data, it can be assumed that the clinical manifestations were due to 4F-MPH only.",
author = "Pietro Papa and Antonella Valli and {Di Tuccio}, Marcello and Giampietro Frison and Flavio Zancanaro and Eleonora Buscaglia and Locatelli, {Carlo Alessandro}",
year = "2019",
month = "6",
day = "1",
doi = "10.1093/jat/bkz001",
language = "English",
volume = "43",
journal = "Journal of Analytical Toxicology",
issn = "0146-4760",
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T1 - Analytically Confirmed Intoxication by 4-Fluoromethylphenidate, an Analog of Methylphenidate

AU - Papa, Pietro

AU - Valli, Antonella

AU - Di Tuccio, Marcello

AU - Frison, Giampietro

AU - Zancanaro, Flavio

AU - Buscaglia, Eleonora

AU - Locatelli, Carlo Alessandro

PY - 2019/6/1

Y1 - 2019/6/1

N2 - 4-Fluoromethylphenidate (4F-MPH) is an halogenated derivative of methylphenidate (MPH), a re-uptake inhibitor for dopamine and norepinephrine used for the treatment of attention deficit hyperactivity disorders. In the last few years, several compounds structurally related to MPH have been marked as new psychoactive substances (NPS) with stimulating and euphoric effects similar to the parent drug, but with more dopaminergic activity. This report represents the first case of an analytically confirmed non-fatal intoxication by 4F-MPH. A 26-year-old female was admitted to the emergency department with neuropsychiatric and cardiologic symptoms that lasted for a week, during which she sniffed a powder named 4F-MPH acquired as entactogen on the Internet. The patient required sedation with intravenous diazepam and was discharged two days later with a prescription of promazine and quetiapine. The seized product was analytically characterized by gas chromatography-mass spectrometry, liquid chromatography high-resolution mass spectrometry and nuclear magnetic resonance. These analyses confirmed the composition of the product as a 4F-MPH diastereomeric (±)-threo and (±)-erythro mixture, with a large preponderance of the active (±)-threo isomer. A minimal validation, intended for rare analytes, was performed for the quantification of 4F-MPH in the biological samples by liquid chromatography-tandem mass spectrometry. Accuracy (bias) and precision were within ±15% for both blood and urine. The blood and urine concentration of (±)-threo 4F-MPH were 32 ng/mL and 827 ng/mL, respectively. Analyses for classic drugs (opiates, methadone, cocaine, cannabis metabolites, amphetamines, ecstasy and LSD), ethanol, qualitative full screen by gas chromatography-mass spectrometry and targeted analysis for 50 NPS by liquid chromatography-tandem mass spectrometry tested negative; comorbidities were excluded, too. Based on these data, it can be assumed that the clinical manifestations were due to 4F-MPH only.

AB - 4-Fluoromethylphenidate (4F-MPH) is an halogenated derivative of methylphenidate (MPH), a re-uptake inhibitor for dopamine and norepinephrine used for the treatment of attention deficit hyperactivity disorders. In the last few years, several compounds structurally related to MPH have been marked as new psychoactive substances (NPS) with stimulating and euphoric effects similar to the parent drug, but with more dopaminergic activity. This report represents the first case of an analytically confirmed non-fatal intoxication by 4F-MPH. A 26-year-old female was admitted to the emergency department with neuropsychiatric and cardiologic symptoms that lasted for a week, during which she sniffed a powder named 4F-MPH acquired as entactogen on the Internet. The patient required sedation with intravenous diazepam and was discharged two days later with a prescription of promazine and quetiapine. The seized product was analytically characterized by gas chromatography-mass spectrometry, liquid chromatography high-resolution mass spectrometry and nuclear magnetic resonance. These analyses confirmed the composition of the product as a 4F-MPH diastereomeric (±)-threo and (±)-erythro mixture, with a large preponderance of the active (±)-threo isomer. A minimal validation, intended for rare analytes, was performed for the quantification of 4F-MPH in the biological samples by liquid chromatography-tandem mass spectrometry. Accuracy (bias) and precision were within ±15% for both blood and urine. The blood and urine concentration of (±)-threo 4F-MPH were 32 ng/mL and 827 ng/mL, respectively. Analyses for classic drugs (opiates, methadone, cocaine, cannabis metabolites, amphetamines, ecstasy and LSD), ethanol, qualitative full screen by gas chromatography-mass spectrometry and targeted analysis for 50 NPS by liquid chromatography-tandem mass spectrometry tested negative; comorbidities were excluded, too. Based on these data, it can be assumed that the clinical manifestations were due to 4F-MPH only.

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