Related Experiment Video
Updated: Apr 11, 2026
11:44
Synthesis and Mass Spectrometry Analysis of Oligo-peptoids
Published on: February 21, 2018
11.5K
β-Methylphenylethylamines: common fragmentation pathways with amphetamines in electrospray ionization
David H Brown1,2, Robert Hansson1, Francois Oosthuizen1
1Forensic Toxicology Section, Forensic Science Laboratory, ChemCentre, Western Australia.
Drug Testing and Analysis
|May 28, 2015
Summary
β-Methylphenylethylamines in supplements can be misidentified as amphetamines due to similar mass spectrometry fragmentation. Careful analysis of fragmentation energies and product ion ratios in LC-MS/MS can differentiate them, preventing misidentification.
Area of Science:
- Analytical Chemistry
- Forensic Science
- Pharmacology
Background:
- β-Methylphenylethylamines are positional isomers of amphetamines found in sporting supplements.
- Gas chromatography-electron ionization-mass spectrometry (GC-EI-MS) shows distinct fragmentation for these isomers.
- Electrospray ionization (ESI) in liquid chromatography-mass spectrometry (LC-MS) results in nearly identical fragmentation patterns for isomeric pairs.
Purpose of the Study:
- To investigate the potential for misidentification of β-methylphenylethylamines as amphetamines in LC-MS analysis.
- To explore methods for distinguishing these isomers in analytical testing.
- To report the presence of β-methylphenylethylamines in sporting supplements and oral fluid samples.
Main Methods:
- Comparison of fragmentation patterns in GC-EI-MS and LC-MS (ESI).
- Utilized liquid chromatography-tandem mass spectrometry (LC-MS/MS) with controlled fragmentation energies.
- Examined product ion abundances (qualifier ratios) from collision-induced dissociation.
- Analyzed mass spectra from liquid chromatography-electrospray ionization-quadrupole time of flight (LC-ESI-QTOF).
Main Results:
- Identical fragmentation observed for β-methylphenylethylamine/amphetamine and N-methyl-β-methylphenylethylamine/methylamphetamine pairs under ESI conditions.
- LC-MS/MS with controlled fragmentation or analysis of qualifier ratios allows differentiation.
- LC-ESI-QTOF systems require retention time separation for accurate identification.
- β-Methylphenylethylamine and N-methyl-β-methylphenylethylamine were detected in supplements and oral fluid samples.
Conclusions:
- Misidentification of β-methylphenylethylamines as amphetamines is possible in LC-MS due to similar fragmentation.
- Specific LC-MS/MS techniques (fragmentation energy control, qualifier ratios) can distinguish these isomers.
- Retention time is critical for differentiation in LC-ESI-QTOF analysis.
- The presence of these compounds in supplements and forensic samples highlights the need for accurate analytical methods.
Related Concept Videos
00:55Mass Spectrometry: Amine Fragmentation
2.6K
Amines can be identified using mass spectroscopy based on their characteristic fragmentation patterns. The molecular ions of amines undergo fragmentation via ⍺-cleavage. The ⍺-cleavage of the carbon-carbon bonds in amines generates an alkyl radical and resonance-stabilized nitrogen-containing cation.
In amines, the number of nitrogen atoms affects the mass of the molecular ion, which is described by the nitrogen rule of mass spectrometry. This rule states that a compound containing a single...
In amines, the number of nitrogen atoms affects the mass of the molecular ion, which is described by the nitrogen rule of mass spectrometry. This rule states that a compound containing a single...
2.6K
01:20Mass Spectrometry: Molecular Fragmentation Overview
6.7K
The ionization of a molecule into a molecular ion inside the mass spectrometer causes instability in the molecule's structure due to the loss of an electron. This eventually leads to the fragmentation or breaking of some bonds in the molecule. The fragmentation occurs predominantly at specific bonds to yield relatively stable fragments.
One type of fragmentation pattern is the cleavage of a single bond in the molecular ion. The cleavage leads to a radical and a cation. The cleavage can occur at...
One type of fragmentation pattern is the cleavage of a single bond in the molecular ion. The cleavage leads to a radical and a cation. The cleavage can occur at...
6.7K
01:01Mass Spectrometry: Carboxylic Acid, Ester, and Amide Fragmentation
2.9K
The fragmentation patterns observed for compounds such as carboxylic acids, esters, and amides in the mass spectra include ⍺-cleavage and McLafferty rearrangement. Fragmentation by ⍺-cleavage preferentially occurs at the carbon-carbon bond at the ⍺-position next to the carboxylic group to generate a neutral radical and a cation. Long chain compounds with hydrogen at their γ-carbon undergo McLafferty rearrangement to give a radical cation and a neutral alkene.
For example, the...
For example, the...
2.9K
01:15Mass Spectrometry of Amines
5.6K
In mass spectroscopy, amines undergo fragmentation to give parent ions with odd molecule weights. This observed mass spectrum follows the nitrogen rule; a molecule with an odd number of nitrogen atoms produces a molecular ion with an odd molecular weight. Amines undergo fragmentation through α cleavage, producing nitrogen-containing cations—iminium ions—and alkyl radicals. Mass spectra of aromatic and cyclic aliphatic amines exhibit strong molecular ion peaks, but acyclic...
5.6K
01:29Mass Spectrometry: Branched Alkane Fragmentation
2.0K
This lesson delves into the mass spectrometry of branched alkane fragmentation. Branched alkanes possess secondary or tertiary carbon atoms, which generate relatively stable carbocations if the cleavage occurs at the branching point. The high stability of carbocations drives the instant fragmentation of branched alkanes. Accordingly, the branched alkane's molecular ion peak is very weak or invisible in the mass spectra, especially in comparison to a linear alkane.
2.0K
01:21Chemical Ionization (CI) Mass Spectrometry
1.7K
The molecular ion peak of a molecule in the mass spectrum provides vital information for molecular identification. However, conventional electron impact ionization can lead to the rapid dissociation of some molecular ions before they reach the detector. A milder ionization method is required to increase the lifetime of such ionized analyte molecules. Chemical ionization (CI) is a gas-phase protonation reaction useful for mass-analyzing analyte molecules that are easily protonated to yield the...
1.7K