REVIEW ARTICLE
New Psychoactive Substances: Chemistry, Pharmacology,
Metabolism, and Detectability of Amphetamine
Derivatives With Modified Ring Systems
Jessica Welter-Luedeke, MSc*† and Hans H. Maurer, PhD*
Abstract: In recent years, new amphetamine derivatives with
modified ring systems were sold and consumed as new drugs of
abuse. They belong together with other new drugs of abuse classes to
the so-called new psychoactive substances (NPS). The chemistry,
pharmacology, toxicology, metabolism, and toxicokinetics are
shortly discussed of camfetamine, 3 methylphenyl-amphetamines
(2-MA, 3-MA, and 4-MA), 2-methiopropamine (2-MPA), and 5-(2-
aminopropyl)benzofuran (5-APB), 6-(2-aminopropyl)benzofuran
(6-APB, so-called “benzofury”) and their N-methyl derivatives
5-MAPB and 6-MAPB. Only a rough assessment of the pharmacol-
ogy and toxicology NPS can be performed in most cases using
published data of analogs, trip reports, and described clinical cases.
Accordingly, they all act more or less as central nervous stimulants
mainly by increasing the concentration of the neurotransmitters nor-
adrenaline, dopamine, and serotonin (5-HT) by inducing their release
and reuptake inhibition. Thus, the acute toxicity is associated with
the sympathomimetic effects, such as mydriasis, hyperthermia,
hypertension, tachycardia, insomnia, and anxiety. With the exception
of 5- and 6-APB, these NPS were extensively metabolized by
N-demethylation and/or aromatic hydroxylation catalyzed by various
cytochrome P450 isoenzymes followed by partial glucuronidation
and/or sulfation. For urinalysis, the unchanged drugs and/or the
nor-metabolites are the main targets.
Key Words: drugs of abuse, designer drugs, new psychoactive sub-
stances, pharmacology, metabolism
(Ther Drug Monit 2016;38:4–11)
INTRODUCTION
In recent years, the term of new psychoactive sub-
stances (NPS) has gained more and more importance.1,2 NPS
shall mimic the effects of known illegal drugs of abuse, for
example hallucinogens or stimulants. They are sold through
the Internet Web sites as “research chemicals,” “bath salts,”
or “legal highs.” As soon as NPS are scheduled, new
Received for publication June 24, 2015; accepted August 14, 2015.
From the *Department of Experimental and Clinical Toxicology, Institute of
Experimental and Clinical Pharmacology and Toxicology, Saarland Uni-
versity, Homburg, Saarland; and †Present address: Department of Forensic
Toxicology, Institute of Forensic Medicine, Ludwig-Maximilians Univer-
sity, Munich, Germany.
The authors declare no conflict of interest.
Correspondence: Hans H. Maurer, PhD, Department of Experimental and
Clinical Toxicology, Saarland University, D-66421 Homburg, Saarland,
Germany (e-mail: hans.maurer@uks.eu).
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
4 Ther Drug Monit  Volume 38, Number 1, February 2016
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
derivatives appear on the market. Therefore, the number of
newly reported NPS by the European Monitoring Centre of
Drug and Drug Addiction (EMCDDA) and the United Na-
tions Office on Drugs and Crime (UNODC) increases each
year.3,4 For example, member states of the European Union
reported 81 NPS to the EMCDDA in 2013 and 101 in 2014,
most of them being synthetic cannabinoids, cathinones, and
phenethylamines. Usually, only little information is avail-
able on pharmacology and toxicology, toxicokinetics, or
detectability in body samples of such new compounds. Cor-
responding data of classic amphetamines,5 2,5-dimethoxy
phenylalkylamines, beta-keto amphetamines, phencyclidine
derivatives, herbal drugs,6 amphetamine-derived designer
drugs, piperazines, and pyrrolidinophenones,7 and finally
of the so-called 2C (phenethylamine) drugs, beta-keto
designer drugs, tryptamines, and fentanyls,8 have already
been reviewed. In the following, corresponding data will
be discussed of new derivatives of amphetamine and meth-
amphetamine with modified ring systems, such as camfet-
amine (CFA), three methyl-(phenyl)-amphetamines (2-MA,
3-MA, and 4-MA), 2-methiopropamine (2-MPA), and 5-(2-
aminopropyl)benzofuran (5-APB), 6-(2-aminopropyl)benzofu-
ran (6-APB, so-called benzofury) and their N-methyl deriva-
tives N-methyl-5-(2-aminopropyl)benzofuran (5-MAPB) and
N-methyl-6-(2-aminopropyl)benzofuran (6-MAPB). The
chemical structures are depicted in Table 1.
CAMFETAMINE
Among the new amphetamine derivatives with modified
ring systems, camfetamine (N-methyl-3-phenyl-norbornan-2-
amine, CFA) is the only compound with a ring system at the
alkyl chain. The norbornane amine structure contains the
isopropyl amine backbone of amphetamines. In contrast to its
N-ethyl analog fencamfamine (N-ethyl-3-phenyl-norbornan-2-
amine; FCF), developed in the 1960s as appetite suppressant,
CFA is not (yet) scheduled in Germany, but ongoing use was
supposed.26
So far, no pharmacological studies on CFA have been
published. According to the described effects on the
Internet drug forums (eg, www.bluelight.org, www.land-
der-traeume.de), such as stimulation and increased vigi-
lance, and the structural similarity to FCF, it can be
assumed that CFA may act in a similar way as FCF. This
was described as a central nervous stimulant because of
its dopamine (DA) reuptake inhibition potential and the
DA and noradrenaline (NA) releasing properties.27–30 In
 Ther Drug Monit  Volume 38, Number 1, February 2016 Amphetamine-Derived New Psychoactive Substances

TABLE 1. Concentrations of 5-MeO-DIPT and Its Metabolites in Biologic Fluids

Compound Name Chemistry Pharmacology Toxicology Metabolism Detectability Ref.
Camfetamine No data published No data or case Pathways proposed CFA, the hydroxy- 9
(CFA) reports published after metabolite aryl and
identification in rat N-demethyl
urine and/or human metabolites are
liver microsome targets for urine
incubations screening by GC-
MS or LC-MSn
N-Demethylation
(CYP2B6,
CYP2C19,
CYP2D6, CYP3A)
Trip reports: Aromatic
Stimulation, hydroxylation
increased (CYP2C19,
vigilance CYP2D6)
Aliphatic hydroxylation
(CYP1A2, CYP2B6,
CYP2C19,
CYP3A4)
Aromatic
di-hydroxylation
followed by
O-methylation
Glucuronidation and
partly sulfation of the
hydroxy metabolites
2-Methyl- Releaser of DA No data or case Pathways proposed 2-MA and the 10–17
amphetamine NA, 5-HT reports published after metabolite hydroxy-aryl
(2-MA) identification in rat metabolite are
urine and/or human targets for urine
liver microsome screening by GC-
incubations MS or LC-MSn
Mainly aromatic
hydroxylation
(CYP2D6) followed
by partial
glucuronidation or
sulfation
Aliphatic hydroxylation
Hydroxylation at the
benzyl group
followed by
oxidation to the
corresponding
carboxylic acid
Aromatic
bis-hydroxylations
followed by
O-methylation

(continued on next page )

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 Welter-Luedeke and Maurer Ther Drug Monit  Volume 38, Number 1, February 2016

TABLE 1. (Continued ) Concentrations of 5-MeO-DIPT and Its Metabolites in Biologic Fluids

Compound Name Chemistry Pharmacology Toxicology Metabolism Detectability Ref.
3-Methyl- Releaser of DA No data or case Pathways proposed 3-MA and the 10–17
amphetamine NA, 5-HT reports published after metabolite hydroxy-aryl
(3-MA) identification in rat metabolite are
urine and/or human targets for urine
liver microsome screening by GC-
incubations MS or LC-MSn
Mainly aromatic
hydroxylation
(CYP2D6) followed
by partial
glucuronidation
Aliphatic hydroxylation
Hydroxylation at the
benzyl group
followed by
oxidation to the
corresponding
carboxylic acid
Aromatic
bis-hydroxylations
followed by
O-methylation
4-Methyl- Releaser of DA 16 deaths Pathways proposed 4-MA and the 10–18
amphetamine NA, 5-HT associated with after metabolite hydroxy-aryl
(4-MA) 4-MA identification in rat metabolite are
urine and/or human targets for urine
liver microsome screening by GC-
incubations MS or LC-MSn
Mainly aromatic
hydroxylation
(CYP2D6) followed
by partial
glucuronidation
Aliphatic hydroxylation
Hydroxylation at the
benzyl group
followed by
oxidation to the
corresponding
carboxylic acid
2-Methiopropamine Inhibitor of NA and Acute poisoning Pathways proposed 2-MPA and its 19,20
(2-MPA) DA reuptake with insomnia, after metabolite N-demethyl
nausea, and identification in rat metabolite are
cardiovascular and human urine targets for urine
symptoms and/or human liver screening by GC-
microsome MS or LC-MSn
incubations
N-Demethylation
(CYP1A2, CYP2B6,
CYP2C19,
CYP2D6, CYP2E1,
CYP3A4)
Hydroxylation at the
side chain (CYP1A2,
CYP2C19,
CYP2D6, CYP3A4)
followed by
oxidation to the
corresponding
ketone
Glucuronidation or
sulfation of the
hydroxy metabolites

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 Ther Drug Monit  Volume 38, Number 1, February 2016 Amphetamine-Derived New Psychoactive Substances

TABLE 1. (Continued ) Concentrations of 5-MeO-DIPT and Its Metabolites in Biologic Fluids

Compound Name Chemistry Pharmacology Toxicology Metabolism Detectability Ref.
5-(2-Aminopropyl) Bioisosteric to Two deaths Pathways proposed 5-APB is the target 19,21–23
benzofuran MDA associated with after metabolite for urine
(5-APB) 5-APB identification in rat screening by GC-
and human urine MS or LC-MSn
and/or human liver
microsome
incubations
Inhibitor of DA Only minor metabolism
NA, 5-HT
transporters
Ligands of 5-HT2A Ring cleavage through
and 5-HT2B several steps
receptors
Hydroxylation
Hydrogenation
Deamination
6-(2-Aminopropyl) Bioisosteric to Acute poly drug Pathways proposed 6-APB is the target 19,24,25
benzofuran MDA poisoning with after metabolite for urine
(6-APB) agitation, acute identification in rat screening by GC-
psychosis urine and/or human MS or LC-MSn
liver microsome
incubations
Inhibitor of DA Only minor
NA, 5-HT metabolism:
transporters
Ligands of 5-HT2A Deamination
and 5-HT2B
receptors
N-Methyl-5-(2- Bioisosteric to No data or case Pathways proposed 5-MAPB and its 23
aminopropy) MDMA, no reports published after metabolite N-demethyl
benzofuran further data identification in rat metabolite are
(5-MAPB) available and human urine targets for urine
and/or human liver screening by GC-
microsome MS or LC-MSn
incubations
Only minor metabolism
N-Demethylation
(CYP1A2, CYP2B6,
CYP2C19,
CYP2D6)
Ring cleavage through
several steps
Hydroxylation
Hydrogenation
N-Methyl-6-(2- Bioisosteric to No data or case Pathways proposed 6-MAPB and its 25
aminopropyl) MDMA, no reports published after metabolite N-demethyl
benzofuran (6- further data identification in rat metabolite are
MAPB) available urine and/or human targets for urine
liver microsome screening by GC-
incubations MS or LC-MSn
Only minor metabolism
N-Demethylation
(CYP1A2, CYP2D6,
CYP3A4)
Ring cleavage through
several steps
Hydroxylation
Hydrogenation

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 Welter-Luedeke and Maurer
addition, FCF showed addiction potential and reduction of
body weight.31–35
However, metabolism and detectability of CFA were
studied. The main metabolic steps detected for CFA in
rat urine and/or human liver microsome incubations were
N-demethylation, aromatic and aliphatic hydroxylation, aro-
matic di-hydroxylation followed by O-methylation, and com-
binations of these steps.9 The main human cytochrome P450
(CYP) isoenzymes involved in aromatic hydroxylation were
CYP2C19 and CYP2D6, for the N-demethylation CYP2B6,
CYP2C19, CYP2D6, and CYP3A4, whereas the aliphatic
hydroxylation was catalyzed by CYP1A2, CYP2B6,
CYP2C19, and CYP3A4. Glucuronidation of almost all
hydroxylated metabolites could also be observed, and a few
sulfates. CFA underwent an extensive metabolism resulting in
hydroxy-aryl and nor CFA, which were the most abundant
compounds besides CFA in urine, and therefore, the targets
for urine screening by GC-MS or LC-MSn.9
METHYLPHENYL-AMPHETAMINES
Methyl substitution of the amphetamine phenyl ring led to
three isomeric NPS, namely 2-, 3-, or 4-methyl-amphetamine
(2-MA, 3-MA, or 4-MA). 4-MA was developed in the 1950s as
appetite suppressant but was never marketed. Its renaissance
began in 2010 when it was seized in Germany as powder labeled
as amphetamine.36 EMCDDA reported sales of 4-MA in several
other countries.18 Analyses of the powders showed varying
amounts of amphetamine, 4-MA, and caffeine. After European
Union–wide control of 4-MA, its isomer 2-MA could be found
on the Internet Web sites offering legal highs. The third isomer
3-MA has not (yet) reached importance on the NPS market.
All 3 compounds are potent releasers for monoamines,
and it could be shown that the releasing potencies for DA and
NA were similar to that of amphetamine but higher for
serotonin (5-HT) release.10–16 2-MA seemed to be the most
potent isomer according to Higgs and Glennon.37
So far, at least 16 deaths associated with ingestion of
4-MA were reported to the EMCDDA.18 Blanckaert et al38 pub-
lished a report about the phenomenon of 4-MA-contaminated
“speed” (amphetamine preparation), which led to several
fatalities in Belgium and in the Netherlands. Postmortem
4-MA concentrations in femoral blood were higher than
amphetamine concentrations. The suggested reasons for
such deaths was on the one hand the increased serotonergic
effects of 4-MA compared with amphetamine and on the
other hand redosing due to underestimated onset or the
dampened psychoactive effect when using 4-MA together
with amphetamine. A trip report published by Bal et al in
1989 showed that 4-MA together with its N-methyl deriva-
tive has already been sold as amphetamine in the past. The
described side effects in this report were mydriasis, hyper-
thermia, hypertension, tachycardia, insomnia, and anxiety.39
These effects are in accordance with the described effects in
other case and trip reports.
Metabolism and detectability studies on the 3 isomers
showed differences in intensity and amount of different
metabolites formed, most probably due to the different position
of the methyl group at the ring, and therefore, a different fitting
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Ther Drug Monit  Volume 38, Number 1, February 2016
into the active center of the corresponding enzymes.17 2-MA
showed the highest amount of metabolites, followed by 3-MA
and 4-MA. Altogether, aromatic hydroxylation was the most
important metabolic step detected for all 3 isomers. In addition,
aliphatic hydroxylation and hydroxylation at the benzyl group
followed by oxidation to the corresponding carboxylic acid
was found. Two hydroxylations at the ring followed by
O-methylation could be observed for 2-MA and 3-MA but
not for 4-MA. Glucuronidation and sulfation played only
a minor role. Nevertheless, at least one glucuronide could be
detected for each isomer and sulfates could be detected for
2-MA. The only human CYP isoenzyme involved in the aro-
matic hydroxylation, as the main step for all 3 isomers, was
CYP2D6, which is known to catalyze the aromatic hydroxyl-
ation of amphetamines.40
The main metabolites for all three isomers and hence,
the targets for urinalysis were the hydroxy-aryl metabolites,
which were excreted in even higher amounts than the parent
compounds at least in rat urine.17 To differentiate an intake of
the controlled 4-MA from that of 2-MA or 3-MA, separation
in urine samples was successfully performed by GC-MS after
solid-phase extraction and heptafluoro-n-butyrylation. The
elution order was the same as already described for the
acetyl-derivatives by Davis et al,41 namely 3-MA,4-
MA,2-MA. In addition to this method, Power et al described
the identification of 4-MA and by-products in forensic sam-
ples allowing differentiating the isomers. 4-MA was inte-
grated in an LC-TOF screening for whole blood42 or in an
LC-MS/MS screening for oral fluid.43
2-METHIOPROPAMINE
The first amphetamine with a completely modified
aromatic ring discussed here is 2-methiopropamine (2-MPA,
1-(thiophen-2-yl)-2-methylaminopropane). It contains the
same side chain as methamphetamine, but the phenyl ring
was bioisosterically substituted by a thiophene ring. Its first
appearance as stimulant on drug forums and Web sites
supplying legal highs was in 2010. In some countries,
2-MPA is a controlled substance, but the ongoing discussion
on drug forums and the fact that it is still offered on the
Internet Web sites show its continuing relevance on the drug
market. 2-MPA was already synthesized in 1942 by Blicke
and Burkhalter.44 It was tested for its pharmacological prop-
erties, and these were similar to methamphetamine regarding,
eg, pressor activity. This is in accordance with recent studies
showing that 2-MPA acts as NA and DA reuptake inhibitor
not exactly as potent as amphetamine but in a similar range.19
Trip reports further support these effects describing stimula-
tion with mild euphoria and as adverse effects tachycardia,
hypertension, and increased sweating (eg, www.bluelight.org
and www.land-der-traeume.de). A case of acute poisoning
after ingestion of 2-MPA was described by Lee et al.20 They
documented after an intake of 50 mg “Quicksilver” (a product
contained most likely MPA) insomnia, nausea, and cardio-
vascular symptoms.
Concerning toxicokinetics, only the metabolism and
detectability in urine were studied so far. The main bio-
transformation steps were N-demethylation, hydroxylation at
 Ther Drug Monit  Volume 38, Number 1, February 2016
the side chain followed by oxidation to the corresponding
keto compound, or mono- and di-hydroxylation at the thio-
phene ring followed by O-methylation. Combinations of these
steps could also be observed. Further glucuronidation and
sulfation of the hydroxy metabolites could be found in rat
and human urine.45 Regarding the involved human CYP iso-
enzymes in the main metabolic steps, CYP1A2, CYP2B6,
CYP2C19, CYP2D6, CYP2E1, and CYP3A4 catalyzed
N-demethylation, whereas CYP1A2, CYP2C19, CYP2D6,
CYP2E1, and CYP3A4 were responsible for the ring hydrox-
ylation and CYP1A2, CYP2C19, CYP2D6, and CYP3A4 for
the hydroxylation at the side chain. Interestingly, the isoen-
zymes involved in N-demethylation and ring hydroxylation
were more or less the same as for methamphetamine.45
For identification of 2-MPA in powder samples, an
analytical profile was published by the US Drug Enforcement
Administration (DEA) and another publication described the
synthesis and the analytical separation of 2-MPA and its
positional isomer 3-MPA.46,47 Schaeper et al48 also published
a report about its analytical characterization. In biological
samples, detection of 2-MPA has to be focused on 2-MPA
itself and the nor metabolite as shown in rat and human urine
samples.45
BENZOFURAN-CONTAINING DRUGS
Another ring modification was realized by “adding”
a furan ring to the benzene ring resulting in benzofuran analogs
of amphetamine and methamphetamine. This drug class consists
of 5-(2-aminopropyl)benzofuran (5-APB), 6-(2-aminopropyl)
benzofuran (6-APB, so-called benzofury) and their N-methyl
derivatives N-methyl-5-(2-aminopropyl)benzofuran (5-MAPB)
and N-methyl-6-(2-aminopropyl)benzofuran (6-MAPB).
They are not only related to the stimulants amphetamine
and methamphetamine but also to the entactogenic designer
drugs 3,4-methylenedioxyamphetamine (MDA) and 3,4-
methylenedioxymethamphetamine (MDMA, ecstasy). They
can be recognized as analogs, where one oxygen in the methy-
lenedioxy ring was replaced by methine (-CH = ). Therefore,
it is not surprising that the described effects on drug users’
forums, such as www.bluelight.org are more similar to MDA
and MDMA.
These compounds started to appear consecutively since
2010 when users started to discuss their effects. In Germany,
only 5-APB and 6-APB were controlled but in the United
Kingdom all 4 of them. They were all consumed as
stimulating or entactogenic drugs, with euphoric and empa-
thogenic effects (eg, https://drugs-forum.com and www.
bluelight.org). The described adverse effects are also typical
for stimulants, for example tachycardia, hypertension, hyper-
thermia, insomnia, and anxiety. These trip reports reflect
again the scientific pharmacology studies. Iversen et al19
tested the effects and binding activities of 5-APB and
6-APB on different transporters and receptors. They could
show that their inhibitory effects on dopamine transporter,
noradrenaline transporter, and serotonin transporter were sim-
ilar to amphetamine, but with higher affinities on serotonin
transporter, especially for 5-APB. They could also show that
5-APB and 6-APB have high binding activity to 5-HT2A and
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Amphetamine-Derived New Psychoactive Substances
5-HT2B receptors. Furthermore, 6-APB showed high affinity
for the a2C-adrenoceptor. These results could explain the
MDA-like effects as MDA also affects the 5-HT release.
The 5-HT2B receptor was suspected to be involved in cardi-
otoxicity after long-term use of stimulants such as MDMA,
and the 5-HT2A receptor was believed to be involved in hal-
lucinogenic effects.49–51 In another recent publication by
Rickli et al,52 the inhibitory and releasing properties of
5-APB and 6-APB together with other benzofuran-related
compounds were investigated. The results were mainly in
accordance with those of Iversen et al,19 showing that
5-APB and 6-APB block the monoamine transporters, induce
transporter-mediated monoamine release similarly to MDMA
and also directly stimulate adrenergic and serotonergic recep-
tors. Unfortunately, for the N-methyl derivatives such studies
have not been performed. Nevertheless, due to the similar
structure and the pharmacological effects described by users,
it is quite probable that they act similar as 5-APB and 6-APB.
Two deaths associated with the intake of 5-APB have
been published. In the report where only 5-APB was taken,
the decedent was freezing, hallucinating, and had difficulties
in breathing as described by witnesses. He collapsed, became
unresponsive and the emergency personnel found him
asystolic and apneic.21 The second case was a fatal intoxica-
tion after ingestion of high amounts of 5-APB and the cath-
inone 3-methyl-N-methylcathinone (3-MMC).22 The patient
showed agitation, seizures, tachycardia, hyperthermia and
died 4 hours after ingestion of the drugs. The cause of death
was cardiovascular collapse after ingestion of a mixture of
NPS. Poly-drug use is always a health threat as no one could
estimate the additive effects of drugs of abuse mixtures.
Another example for this aspect was published by Chan
et al.24 Agitation and acute psychosis were described after
ingestion of 6-APB together with cannabis and several other
substances (amphetamine, chloroquine, ketamine, and ephed-
rine). The patient recovered after 5 days hospitalization.
Again, the metabolism and detectability in urine were
studied revealing that the metabolism of these 4 benzofuran-
containing compounds was not extensive.23,25 N-Demethyla-
tion was the main metabolic step observed for 5- and
6-MAPB. In addition, ring cleavage initiated by hydroxylation
at the furan ring system led to an unsaturated aldehyde. This
was reduced to the corresponding aldehyde and afterward either
reduced to the corresponding alcohol or oxidized to the corre-
sponding carboxylic acid. These metabolites could be observed
for all four compounds although the amounts were not predom-
inant. Minor metabolic steps were di-hydroxylation of the
5-isomers, hydrogenation of 5-APB, 5-MAPB, and 6-MAPB
as well as deamination of 5- and 6-APB. An initial CYP activity
screening was only evaluable for N-demethylation of 5-MAPB
and 6-MAPB. The human CYP isoenzymes involved in
the 5-MAPB N-demethylation were CYP1A2, CYP2B6,
CYP2C19, and CYP2D6, whereas CYP1A2, CYP2D6, and
CYP3A4 catalyzed the 6-MAPB N-demethylation. Altogether,
there were only a few small differences in the metabolism of the
5- and 6-isomers, most probably due to lower formation rates
because of the meta-position of the oxygen in the 6-isomers
compared with the para position in the 5-isomers and/or due to
different elimination rates.23,25
9
 Welter-Luedeke and Maurer
For toxicological detection, one should focus on the
parent compounds; and in case of 5- and 6-MAPB addition-
ally on the corresponding nor metabolites as all other
described metabolic steps only play minor roles.
For the separation of the isomers in biological samples,
such as urine or blood, solid-phase extraction followed by
heptafluoro-n-butyrylation could be used as shown by Welter
et al.25 The elution order was 5-APB,6-APB,5-MAPB,6-
MAPB. In addition, only a few data on analytical character-
ization of these drugs in the Internet purchased products have
been published by Casale et al and Stanczuk et al.53,54 They
separated the positional isomers of APB by GC-MS with or
without derivatization.
CONCLUSIONS AND PERSPECTIVES
As the recent drug reports showed, an increasing
number of NPS entered the drugs of abuse market every
year. Toxicologists have to keep track on these trends by
ongoing investigation of the chemical, analytical, toxicolog-
ical, and metabolic properties of them. Only a rough assess-
ment of the pharmacology and toxicology NPS can be
performed in most cases using published data of analogs,19
trip reports, and described clinical cases. Green and Nutt55
stated that pharmacology should be at the center of preclinical
and clinical studies on NPS. Concerning toxicokinetics, at
least several studies on the metabolism and detectability of
NPS were performed, but should be completed by studying
for example, the inhibition potential of NPS on metabolizing
enzymes56,57 or drug transporters.58
ACKNOWLEDGMENTS
The authors would like to thank Dr. Markus R. Meyer
and Achim Caspar for their support.
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