Enantiomeric separation of Novel Psychoactive Substances by capillary electrophoresis using (+)-18-crown-6-tetracarboxylic acid as chiral selector

Article abstract of DOI:10.1002/chir.22981

In the recent years, hundreds of Novel Psychoactive Substances (NPS) have entered both the European and the global drug market. These drugs, which are mainly used for recreational matters, have caused serious social problems. Every year, the spectrum of these misused drugs is enlarged by new derivatives, which are produced by modifications of basic structures of already well-known substances. Additionally, a lot of them possess a stereogenic center which leads to 2 enantiomeric forms. The fact that the pharmacological effects and potencies of the enantiomers of these chiral NPS may differ can be assumed from a broad spectrum of active pharmaceutical ingredients. For this reason, analytical method development regarding enantiomeric separation for these classes of substances is of great pharmaceutical and medical interest. The aim of this work was to create an easy-to-prepare chiral capillary electrophoresis method for the enantioseparation of NPS which contains a primary amino group by means of (+)-18-crown-6-tetracarboxylic acid as chiral selector. Novel Psychoactive Substances were purchased at various Internet stores or represent samples seized by Austrian police. The effects of selector concentration, the electrolyte composition, and the addition of organic modifiers to the background electrolyte on enantioseparation were investigated. Under optimized conditions, the use of 20-mM (+)-18-crown-6-tetracarboxylic acid, 10-mM Tris, and 30-mM citric acid buffer at pH 2.10 turned out to be effective. Fifteen of 24 tested NPS were resolved in their enantiomers within 15?minutes. It was found that all NPS were traded as racemic mixtures.

Full text of DOI:10.1002/chir.22981

Received: 31 January 2018
DOI: 10.1002/chir.22981
Revised: 20 March 2018
Accepted: 23 April 2018
R E G U L A R A R T I C L E
Enantiomeric separation of Novel Psychoactive Substances
by capillary electrophoresis using (+)‐18‐crown‐6‐
tetracarboxylic acid as chiral selector
Johannes S. Hägele | Martin G. Schmid
Department of Pharmaceutical Chemistry,
Abstract
Institute of Pharmaceutical Sciences,
In the recent years, hundreds of Novel Psychoactive Substances (NPS) have
entered both the European and the global drug market. These drugs, which
are mainly used for recreational matters, have caused serious social problems.
Every year, the spectrum of these misused drugs is enlarged by new
derivatives, which are produced by modifications of basic structures of already
well‐known substances. Additionally, a lot of them possess a stereogenic center
which leads to 2 enantiomeric forms. The fact that the pharmacological effects
and potencies of the enantiomers of these chiral NPS may differ can be assumed
from a broad spectrum of active pharmaceutical ingredients. For this reason,
analytical method development regarding enantiomeric separation for these
classes of substances is of great pharmaceutical and medical interest. The aim
of this work was to create an easy‐to‐prepare chiral capillary electrophoresis
method for the enantioseparation of NPS which contains a primary amino group
by means of (+)‐18‐crown‐6‐tetracarboxylic acid as chiral selector. Novel
Psychoactive Substances were purchased at various Internet stores or represent
samples seized by Austrian police. The effects of selector concentration, the
electrolyte composition, and the addition of organic modifiers to the background
electrolyte on enantioseparation were investigated. Under optimized conditions,
the use of 20‐mM (+)‐18‐crown‐6‐tetracarboxylic acid, 10‐mM Tris, and 30‐mM
citric acid buffer at pH 2.10 turned out to be effective. Fifteen of 24 tested NPS
were resolved in their enantiomers within 15 minutes. It was found that all
NPS were traded as racemic mixtures.
University of Graz, Graz, Austria
Correspondence
Martin G. Schmid, Department of
Pharmaceutical Chemistry, Institute of
Pharmaceutical Sciences, University of
Graz, Universitätsplatz 1, A‐8010 Graz,
Austria.
Email: martin.schmid@uni‐graz.at
KEYWORDS
(+)‐18‐Crown‐6‐tetracarboxylic acid, amphetamine, benzofuries, capillary electrophoresis, Novel
Psychoactive Substances (NPS), primary amines
1 | INTRODUCTION
the European as well as the global drug market. By the
end of 2016, the European Monitoring Centre for Drugs
Since the last decade, globalization and the further
technological progress of the Internet modified the drug
market in a drastic way. A huge number of NPS still float
and Drug Addiction (EMCDDA) monitored more than
620 NPS that have appeared in Europe's drug market
and which are often not covered by international drug
Chirality. 2018;1–8.
wileyonlinelibrary.com/journal/chir
© 2018 Wiley Periodicals, Inc.
1

2
HÄGELE AND SCHMID
controls.1 These compounds are mainly produced in
Eastern Europe or in Asian countries and are promoted
and sold via the Internet as “plant food,” “research com-
pounds,” or “bath salts” worldwide. Being misused
mainly for recreational matters, the spectrum of these
substances is continuously enlarged by new derivatives,
which are produced via molecular structure modification
of already existing compounds. Novel Psychoactive
Substances compete with illicit drugs such as cocaine,
opium, or cannabis. In chemical context, these drug
molecules belong to different compound classes like
phenetylamines, arylamines, piperazines, or cathinone
derivatives. In most cases, they are sold as “legal”
replacements for prohibited drugs. Because of their
explicit labeling with disclaimers like “not for human
consumption,” Internet stores sell the compounds with
a very low risk of law enforcement. The simple access
to NPS via the World Wide Web is an immense challenge
and makes the control of the global drug situation more
difficult. Also, online stores offer dubious data about
identity and purity, which should be critically
scrutinized about their correctness. These data collected
by mass spectroscopy or nuclear magnetic resonance
are displayed on vendors' websites pretending quality
assurance of the provided NPS.
An interesting attribute of some of these drug mole-
cules is the presence of an asymmetric carbon atom in
their chemical structure. This plays a very important role
in their pharmacological and toxicological behavior
because stereogenic centers lead to 2 different enantio-
meric forms with potentially different pharmacological
effects and potencies. The fact that enantiomers may
exhibit different effects is well known for a broad spec-
trum of chiral active pharmaceutical ingredients. With
respect to illicit drugs, native amphetamine represents
an example, where the S(+) enantiomer shows higher
potency than its corresponding R(−) enantiomer.2
Regarding methamphetamine, the S(+) enantiomer also
shows higher CNS‐stimulating effects, and for
methcathinone, the S(−) enantiomer leads similarly to
higher stimulation.3,4 However, for the majority of NPS,
there are few data yet available for potential differences
of the effects of the enantiomers. Therefore, analytical
method development for the enantiomeric separation of
these substances is of great importance.
successful enantioseparation, different chiral selectors
such as cyclodextrins, polysaccharide derivatives, and
chiral ion‐exchange type stationary phases were chosen.
Chiral crown ethers turned out to be a suitable chiral
selector class for primary amines.32-35 Crown ethers with
their macrocyclic polyether ring systems were first intro-
duced by Pedersen in 1967.36 For enantioseparation by
CE, particularly (+)‐18‐crown‐6‐tetracarboxylic acid
turned out to be an appropriate chiral selector. Being
used as an additive to the BGE, successful chiral separa-
tion of 4 amino acids was first shown by Kuhn in the
1990s.32 Chiral recognition is based on the formation
of host‐guest inclusion complexes between the chiral
selector and the analyte containing a primary amino
group. Additionally, ion‐dipole interactions can be taken
into account. The different complex stability constants
of the mixed host‐guest complexes with R‐enantiomer
and S‐enantiomer and the different electrophoretical
mobilities of the complexes in CE are responsible for
the enantiomeric discrimination. A scheme of such a tri-
pod interaction between (+)‐18‐crown‐6‐tetracarboxylic
acid molecule and a primary amine is shown in
Figure 1. However, (+)‐18‐crown‐6‐tetracarboxylic acid
was not commercially available for a certain period of
time.34 Because the purchase of this chiral selector has
been continued, the aim of this work was to investigate
its chiral separation ability for NPS with primary amino
structure.
Because many NPS are not yet commercially available
from official distributors of chemicals, they were either
purchased from Internet shops or represent samples
seized by Austrian police. According to our present
knowledge, apart from successful enantioseparation of
amphetamine and para‐chloroamphetamine by CE using
(+)‐18‐crown‐6‐tetracarboxylic acid as chiral additive,26
there is no publication about chiral separation of NPS
with this chiral selector. Therefore, we tested amphet-
amines, benzofurans, and some other psychoactive
substances being traded as NPS as primary amines for
this purpose.
In literature, successful attempts for enantioseparation
of NPS were presented by different high‐performance
separation techniques such as high‐performance liquid
chromatography,5-14 gas chromatography (GC),9,12,15-18
and supercritical fluid chromatography.19 Also with
capillary electrophoresis as well as with capillary
electrochromatography as electrophoretically driven
methods, positive results were achieved.7,17,19-31 For
FIGURE 1 Schematical diagram showing a tripod interaction
between (+)‐18‐crown‐6‐tetracarboxylic acid and a primary amine

HÄGELE AND SCHMID
3
68.5 cm and an effective length of 60 cm, purchased
from MicroQuartz (Munich, Germany). Detection was
performed via on‐column measurements of UV absorp-
tion at 208 nm. All measurements were carried out at
ambient temperature. Before and after each run, the cap-
illary was flushed with 0.2‐M NaOH, water, and BGE,
respectively. Samples were injected dynamically by
applying a pressure of 10 mbar * 5 seconds on the inlet
vial.
2 | MATERIALS AND METHODS
2.1 | Chemicals and solutions
All chemicals were of analytical grade. (+)‐18‐Crown‐6‐
tetracarboxylic acid was purchased in the past from
Merck‐Schwachhardt (Hohenbrunn, Germany). Tris
[Tris(hydroxymethyl)‐aminomethane] was bought from
BioRad Laboratories (Hercules, California). Citric acid
was purchased from Merck (Darmstadt, Germany). Meth-
anol was from VWR Chemicals (Fontenay‐sous‐Bois,
France). Nanopure water was prepared inhouse (Millipore,
Darmstadt, Germany).
2.3 | Sample preparation
Each analyte (1.0 mg) was dissolved in 1 mL of nanopure
water. To accelerate the dissolving process, the samples
were put on an ultrasonic bath for 1 minute prior to
filtration, analog to the procedure the BGE was prepared
and filtered through a 0.45‐μm pore size filter (Carl Roth,
Karlsruhe, Germany).
Amphetamine, D‐amphetamine, 4‐methylthioamphetamine,
2,5‐dimethoxyamphetamine, 4‐dimethoxyamphetamine, 4‐
methoxyamphetamine, 4‐bromo‐2,5‐dimethoxyamphetamine,
4‐methylendioxyamphetamine, 4‐(2‐aminopropyl)benzofuran,
1‐(2,3‐dihydro‐1‐benzofuran‐4‐yl)propan‐2‐amine (4‐APDB),
and 7‐(2‐aminopropyl)benzofuran were purchased from
LGC Standards (Wesel, Germany). Because a part of the
analytes were not commercially available from official sup-
pliers because of their novelty, they were bought from
diverse shops in the Internet. 3‐Fluoroamphetamine, 5‐(2‐
aminopropyl)benzofuran, 6‐(2‐aminopropyl)benzofuran, and
5‐(2‐aminopropyl)indole were obtained from www.
3 | RESULTS AND DISCUSSION
Enantioseparation by chiral crown ethers requests the
presence of a primary amine group in the chiral analyte.
Because this is the case for the drug compound classes
of amphetamines and benzofurans, they were subject to
further investigations. The chemical structures of the
analytes are pictured in Table 1.
sensearomatic.com.
2,5‐Dimethoxy‐4‐chloroamphetamine
and 1‐(2,3‐dihydro‐1‐benzofuran‐5‐yl)propan‐2‐amine were
purchased from www.deboralabs.com. 1‐(2,3‐Dihydro‐1‐
benzofuran‐6‐yl)propan‐2‐amine was purchased from
www.officialbenzofury.com. Thiopropamine was bought
The application of (+)‐18‐crown‐6‐tetracarboxylic
acid for chiral separation of primary amines was first
reported in the literature in the 1990s.32 Based on the
work of Gübitz and Schmid, who used this chiral selector
for enantioseparation of racemic glycyldipeptides and
diastereomeric dipeptides, separation ability was tested
for the aforementioned substance classes being abused
as NPS.37 For preliminary experiments, 3,4‐
dimethoxyamphetamine and 4‐APDB were chosen as
model compounds. An aqueous solution of 20‐mM (+)‐
18‐crown‐6‐tetracarboxylic acid (pH 1.99) served as
electrolyte. In this case, both substances were resolved
in their enantiomers. After these promising results, the
effect of different BGEs as well as different concentrations
of the chiral selector on enantioseparation was checked.
With a BGE of 10 mM of (+)‐18‐crown‐6‐tetracarboxylic
acid, 10‐mM Tris solution, and 10‐mM citric acid (pH
2.47), baseline separations were obtained. For this reason,
the above‐mentioned Tris/citric acid buffer was chosen
for further measurements. The use of 20‐mM (+)‐18‐
crown‐6‐tetra‐carboxylic acid in this BGE (pH 2.22) led
again to better separation results in combination with
only slightly higher migration times. Furthermore, an
increase of citric acid from 10 to 30 mM to acidify the
BGE showed better separation results. For this reason,
from
www.rcnetchemicals.com.
6,7‐Methylendioxy‐2‐
aminotetraline and 4‐fluoroamphetamine represent real‐life
samples seized by Austrian Police. Prior to chiral separation
experiments in CE, the substances were characterized by
GC‐electron impact mass spectrometry and NMR if neces-
sary. The optimized, final BGE was prepared by dissolving
20‐mM (+)‐18‐crown‐6‐tetracarboxylic acid in a mixture of
10‐mM Tris and 30‐mM citric acid in ultrapure water at a
pH of 2.10. Prior to measurements, the solution was degassed
by ultrasonification and was filtered through a 0.45‐μm pore
size nylon filter (Carl Roth, Karlsruhe, Germany). With
respect to the comparability of the separation factors, αapp
(t2/t1) is shown in this work because with (+)‐18‐crown‐6‐
tetracarboxylic acid the EOF was slower than the com-
pounds, and therefore, negative αeff ((t2‐t0)/(t1‐t0)) values
would have been generated.
2.2 | Instrumentation
A fully automated 3DCE system (Agilent Technologies,
CA, USA) equipped with a diode array detector was used
for the experiments. Measurements were performed in
50‐μm ID‐fused silica capillaries with a total length of

4
HÄGELE AND SCHMID
TABLE 1 Chemical structures of the NPS investigated in this study
Amphetamines
Amphetamine
4‐Bromoamphetamine
2‐Chloroamphetamine
(2‐CA)
4‐Fluoroamphetamine
(4‐BA)
(4‐FA)
3‐Fluoroamphetamine
(3‐FA)
2‐Fluoroamphetamine
(2‐FA)
2,5‐Dimethoxyamphetamine
2,5‐Dimethoxy‐4‐chloroamphetamine
(DMA)
(DOC)
4‐Bromo‐2,5‐dimethoxy‐amphetamine
4‐Nitroamphetamine
(4‐NA)
3,4‐Dimethoxyamphetamine
4‐Methylthioamphetamine
(DOB)
(MTA)
4‐Methoxyamphetamine 3,4‐Methylendioxyamphetamine
(MDA)
Benzofuries
4‐(2‐Aminopropyl)‐benzofuran
(4‐APB)
5‐(2‐Aminopropyl)‐benzofuran
(5‐APB)
6‐(2‐Aminopropyl)‐benzofuran
(6‐APB)
7‐(2‐Aminopropyl)‐benzofuran
(7‐APB)
1‐(2,3‐Dihydro‐1‐benzofuran‐4‐yl) 1‐(2,3‐Dihydro‐1‐benzofuran‐5‐yl) 1‐(2,3‐Dihydro‐1‐benzofuran‐6‐yl)
propan‐2‐amine
(4‐APDB)
propan‐2‐amine
(5‐APDB)
propan‐2‐amine
(6‐APDB)
Other psychoactive substances
Thiopropamine
5‐(2‐Aminopropyl)‐1‐methyl‐ethylamine
(5‐API)
6,7‐Methylenedioxy‐2‐aminotetralin
(MDAT)
20‐mM (+)‐18‐crown‐6‐tetracarboxylic acid, 10‐mM Tris
solution, and 30‐mM citric acid (pH 2.10) and a voltage
of 30 kV to the cathode were used as final conditions to
test a set of 24 NPS. Fifteen NPS of different compound
classes were partially or even baseline separated within
15 minutes. Separation data are shown in Table 2. An
electropherogram of the chiral separation of 3,4‐
dimethoxyamphetamine is given in Figure 2.
Additionally, the enantiomeric migration order for
native amphetamine was found to be R(−) before S(+)

HÄGELE AND SCHMID
5
TABLE 2 Separation results of the tested enantiomers using (18)‐crown‐6‐tetracarboxylic acid
Compound
t1 (min)
t2 (min)
αapp
Rs
Amphetamine
10.40
10.50
10.11
10.91
13.11
11.75
12.16
12.79
12.06
11.46
14.46
11.33
13.44
10.48
11.84
14.12
10.89
13.50
12.48
10.99
12.73
9.70
10.58
10.70
10.22
10.98
13.42
11.86
12.69
−
1.017
1.018
1.011
1.006
1.024
1.010
1.044
−
1.29
1.65
0.86
0.54
2.18
0.93
5.07
−
4‐FA
3‐FA
2‐FA
3‐NA
4‐BA
2‐CA
DOC
MTA
−
−
−
DMA
−
−
−
3,4‐Dimethoxyamphetamine
15.11
−
1.046
−
4.65
−
4‐Methoxyamphetamine
DOB
−
−
−
MDA
−
−
−
4‐APB
12.01
14.85
−
1.015
1.051
−
1.19
4.20
−
4‐APDB
5‐APB
5‐APDB
6‐APB
13.74
−
1.018
−
2.00
−
6‐APDB
7‐APB
11.17
12.97
9.87
11.30
−
1.016
1.019
1.018
1.018
−
1.54
1.66
0.94
1.69
−
Thiopropamine
5‐API
11.09
11.28
MDAT
Conditions: 20‐mM (+)‐18‐crown‐6‐tetracarboxylic acid, 10‐mM Tris, 30‐mM citric acid, pH 2.10, cassette temperature: 20°C, applied voltage: 30 kV to the cath-
ode, injection: 10 mbar for 5 seconds, samples: 1 mg/mL in water.
as shown in Figure 3. Enantiomeric migration order
was tested by spiking a sample of racemic amphetamine
with S(+)‐amphetamine. Because no further pure
enantiomers of the other analytes were commercially avail-
able, determination of further EMOs was not possible.
Substances which showed no chiral discrimination
under the optimized conditions were subject of further
separation experiments: A BGE of 40‐mM (+)‐18‐crown‐
6‐tetracarboxylic acid, 10‐mM Tris solution, and 30‐mM
citric acid (pH 2.00) was used. The significantly higher
amount of chiral selector and the further decrease of pH
did not show positive results. Similarly, addition of
organic modifiers such as methanol to the BGE did not
result in any positive impact on enantioseparation or
analysis time.
5‐APDB and 4‐APDB. Furthermore, this approach can not
only be used to separate enantiomers but also to distinguish
clearly between different positional isomers. This is shown
by 3 fluorinated amphetamine derivatives in Figure 5.
Obviously, the analytes only differ in the position of the
fluorine atom but show different migration times. This
approach is advantageous because the positional isomers
can hardly be distinguished by GC‐MS due to their
equal molecular weights. Finally, a validation to prove the
robustness of the method was performed. Results are
shown in Table 3, where both intraday and interday
repeatability by means of 4‐APDB were tested in 5 single
runs, respectively. As the result for intraday measurements,
the RSD of the migration times was less than 0.65% and
for the resolution factor 4.30%. The RSD of the day‐to‐day
measurements for the migration times was below 1.41%
and for the resolution factor 8.19%. In our opinion, these
are acceptable values for the performed CE experiments.
The optimized method was also found to be suitable for
simultaneous enantioseparation of different analytes. An
example is given in Figure 4 showing the analytes 2‐CA,

6
HÄGELE AND SCHMID
FIGURE
4
Simultaneous
chiral
separation
of
2‐
chloroamphetamine, 1‐(2,3‐dihydro‐1‐benzofuran‐4‐yl)propan‐2‐
amine, and 1‐(2,3‐dihydro‐1‐benzofuran‐5‐yl)propan‐2‐amine.
Conditions: 20‐mM (+)‐18‐crown‐6‐tetracarboxylic acid, 10‐mM
Tris, 30‐mM citric acid, pH 2.10, cassette temperature: 20°C, applied
voltage: 30 kV to the cathode, injection: 10 mbar for 5 seconds,
sample: 1 mg/mL in water
FIGURE
2
Single chiral separation of 3,4‐dimethoxy‐
amphetamine using the optimized BGE. Conditions: 20‐mM (+)‐
18‐crown‐6‐tetracarboxylic acid, 10‐mM Tris, 30‐mM citric acid, pH
2.10, cassette temperature: 20°C, applied voltage: 30 kV to the
cathode, injection: 10 mbar for 5 seconds, sample: 1 mg/mL
in water
FIGURE 3 Determination of the enantiomeric migration order
of racemic amphetamine via spiking a racemic amphetamine
sample with S(+)‐amphetamine. Conditions: 20‐mM (+)‐18‐
crown‐6‐tetracarboxylic acid, 10‐mM Tris, 30‐mM citric acid, pH
2.10, cassette temperature: 20°C, applied voltage: 30 kV to the
cathode, injection: 10 mbar for 5 seconds, sample: 1 mg/mL
in water
FIGURE 5 Separation of 3 positional isomers of fluorinated
amphetamine (1: 3‐FA; 2: 4‐FA; 3: 2‐FA). Conditions: 20‐mM (+)‐
18‐crown‐6‐tetracarboxylic acid, 10‐mM Tris, 30‐mM citric acid, pH
2.10, cassette temperature: 20°C, applied voltage: 30 kV to the
cathode, injection: 10 mbar for 5 seconds, sample: 1 mg/mL
in water

HÄGELE AND SCHMID
7
TABLE 3 Repeatability data by means of 4‐APDB including retention time and resolution
Repeatability
t1 (min)
t2 (min)
Rs
Intraday n = 5
14,26 0,14, RSD = 0,65%
14,33 0,28, RSD = 1,41%
14,96 0,13, RSD = 0,61%
15,05 0,25, RSD = 1,32%
4,05 0,23, RSD = 4,30%
4,03 0,49, RSD = 8,19%
Interday n = 5
Conditions: 20‐mM (+)‐18‐crown‐6‐tetracarboxylic acid, 10‐mM Tris, 30‐mM citric acid, pH 2.10, cassette temperature: 20°C, applied voltage: 30 kV to the cath-
ode, injection: 10 mbar for 5 seconds, samples: 1 mg/mL in water.
7. Fillet M, Hubert P, Crommen J. Enantiomeric separations of
drugs using mixtures of charged and neutral cyclodextrins.
4 | CONCLUSION
J Chromatogr A. 2000;875(1–2):123‐134.
In the recent years, NPS gained an enormous popularity
8. Taschwer M, Seidl Y, Mohr S, Schmid MG. Chiral separation of
cathinone and amphetamine derivatives by HPLC/UV using
sulfated β‐cyclodextrin as chiral mobile phase additive.
Chirality. 2014;26(8):411‐418.
worldwide. Every year, the number of these mainly not
scheduled substances is growing continuously. Because
many of these compounds are chiral, analytical method
development for enantioseparation is essential.
With the introduced approach, an easy‐to‐perform,
fast, and reliable chiral CE method for the
enantioseparation of NPS was developed; however, it is
restricted to compounds with a primary amino group.
Under the optimized conditions, 15 of 24 tested NPS were
separated successfully within 15 minutes. Resolution
factors ranged from 0.54 to 5.07.
In the future, the presented technique can be an
additional useful tool for enantiomer and positional
isomer separation of further emerging NPS with a
primary amino group. Additionally, this approach can
9. Weiß JA, Taschwer M, Kunert O, Schmid MG. Analysis of a new
drug of abuse: cathinone derivative 1‐(3,4‐dimethoxyphenyl)‐2‐
(ethylamino)pentan‐1‐one. J Sep Sci. 2015;38(5):825‐828.
10. Silva B, Fernandes C, Tiritan ME, et al. Chiral enantioresolution
of cathinone derivatives present in ‘legal highs’, and
enantioselectivity evaluation on cytotoxicity of 3,4‐
methylenedioxypyrovalerone (MDPV). Forensic Toxicol. 2016;
34(2):372‐385.
11. Wolrab D, Frühauf P, Moulisová A, et al. Chiral separation of
new designer drugs (cathinones) on chiral ion‐exchange type
stationary phases. J Pharm Biomed Anal. 2016;120:306‐315.
12. Weiß JA, Kadkhodaei K, Schmid MG. Indirect chiral separation
help to clarify the enantiomeric status of real‐life samples.
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tive compounds by GC‐MS and HPLC. Sci Justice. 2017;
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ORCID
13. Taschwer M, Grascher J, Schmid MG. Development of an
Martin G. Schmid http://orcid.org/0000-0003-0055-660X
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How to cite this article: Hägele JS, Schmid MG.
Enantiomeric separation of Novel Psychoactive
Substances by capillary electrophoresis using (+)‐
18‐crown‐6‐tetracarboxylic acid as chiral selector.
Chirality. 2018;1–8. https://doi.org/10.1002/
chir.22981
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derivatives used as recreational drugs by cyclodextrin‐modified
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Enantiomeric separation of 13 new amphetamine‐like designer