DSpace at VNU: Rapid determination of scopolamine in evidence of recreational and predatory use

A method for the rapid analysis of suspicious samples was de-veloped, using a portable capillary electrophoresis with contactless conductivity detection.. Therefore, both substances coul

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Technical note

Rapid determination of scopolamine in evidence of recreational and

predatory use

Jorge Sáiza,b, Thanh Duc Maic,d, María López Lópeza,b, Carmen Bartolomée,

Peter C Hauserc, Carmen García-Ruiza,b,⁎

a Department of Chemistry I, Multipurpose Building of Chemistry, University of Alcalá, Ctra Madrid–Barcelona km 33.600, 28871 Alcalá de Henares, Madrid, Spain

b University Institute of Research in Police Sciences (IUICP), University of Alcalá, Ctra Madrid–Barcelona km 33.600, 28871 Alcalá de Henares, Madrid, Spain

c

University of Basel, Department of Chemistry, Spitalstrasse 51, 4056 Basel, Switzerland

d

Centre for Environmental Technology and Sustainable Development (CETASD), Hanoi University of Science, Nguyen Trai Street 334, Hanoi, Viet Nam

e Department of Life Sciences, University of Alcalá, Ctra Madrid–Barcelona km 33.600, 28871 Alcalá de Henares, Madrid, Spain

a b s t r a c t

a r t i c l e i n f o

Article history:

Received 6 March 2013

Received in revised form 31 July 2013

Accepted 5 August 2013

Keywords:

Scopolamine

Burundanga

Predatory drugs

Portable capillary electrophoresis

Contactless conductivity detection

In recent years, scopolamine has become a drug of common use for recreational and predatory purposes and several ways of administration have been devised A method for the rapid analysis of suspicious samples was de-veloped, using a portable capillary electrophoresis with contactless conductivity detection The method allows the separation of scopolamine from atropine which has a similar structure and is present along with scopolamine

in some samples The method was demonstrated to be useful for the fast analysis of several types of evidential items which have recently been reported to have been abused with fatal consequences or employed for criminal purposes An infusion of Datura stramonium L., in which scopolamine and atropine naturally coexist, was ana-lyzed for being frequently consumed for recreational purposes A spiked moisturizing cream and six spiked alco-holic beverages were also analyzed In spite of the complexity of the specimens, the sample pre-treatment methods developed were simple and fast

1 Introduction

Scopolamine is a tropane alkaloid extensively used for clinical

purposes because of its strong parasympatolytic, anticholinergic and

anti-emetic actions [1,2] This alkaloid has an inhibitory effect on

acetylcholine muscarinic receptors, having an inﬂuence on

neurotrans-mission pathways concerning memory It can cause box lock amnesia by

affecting the basal nucleus of Meynert, which is an important structure

for amnesic functions, especially the retention of memory[3] Moreover,

scopolamine can block free will For this reason scopolamine is used

in drug-facilitated robberies and drug-facilitated sexual assaults

Sco-polamine is also known as“burundanga” within the circles of people

who abuse it Scopolamine is tasteless and odorless and can be easily

absorbed in the digestive tract; it can be delivered orally, dermally, or

via inhalation[3] For these reasons, several ways of administration

have been devised by attackers For example, it has been reported that

scopolamine powder can be blown onto the face of the victim, who

will be under the drug's effects within minutes Recently, in Madrid

(Spain), one person was arrested after a complaint from a woman who had been drugged with scopolamine The suspect, who pretended

to be a shaman, took the woman to his house and, after drugging her with a drink to which scopolamine had been added, he sexually assaulted her several times[4] After this case, 38 more women reported having been raped by the same person[5] Moreover, scopolamine has allegedly been added to moisturizing creams, which are applied by the ingenuous victims themselves causing them to be under the inﬂuence

of the drug Scopolamine has also been added to drinks in night clubs

to commit robberies or sexual assaults Approximately one in eight emergency room admissions by poisoning in Bogotá (Colombia) has been attributed to scopolamine[3] However, in spite of its characteris-tics, no mention of scopolamine can be found among information about predatory drugs, for which typical examples are ecstasy, ketamine, Rohypnol, gamma-hydroxybutyrate (GHB), and gamma-butyrolactone (GBL)[6–9]

On the other hand, due to its hallucinogenic effects scopolamine is also used as a recreational drug Like other tropane alkaloids such as at-ropine, scopolamine is produced by plants of the Solanaceae family such

as Hyoscyamus albus L., Datura stramonium L., Mandragora autumnalis Bertol., Scopolia carniolica Jacq., Brugmansia candida Pers., and other plants belonging to the same plant genera Many species of this family are used as food, medicinal, or ornamental plants These plants are naturally distributed throughout the world, but occur mainly in tem-perate regions, and several of them are used in gardening To produce

⁎ Corresponding author at: Department of Chemistry I, Multipurpose Building of

Chemistry, University of Alcalá, Ctra Madrid–Barcelona km 33.600, 28871 Alcalá de

Henares, Madrid, Spain Tel.: +34 91 8856431.

E-mail address: carmen.gruiz@uah.es (C García-Ruiz).

URL: http://www.inquifor.com (C García-Ruiz).

Contents lists available atScienceDirect Science and Justice

j o u r n a l h o m e p a g e : w w w e l s e v i e r c o m / l o c a t e / s c i j u s

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the hallucinogenic effects, they can be smoked and much information

can be found in Internet forums about how to prepare an infusion

from the plants, from either the roots, leaves, stems,ﬂowers, or fruits

and seeds[10,11] Abuse of scopolamine is very risky since its active

dose is very close to the lethal dose Recently, in Madrid (Spain), two

18 year-old men died and one more was hospitalized in serious

condi-tion after drinking an infusion made with seeds[12,13] Additionally,

the Security Forces of Spain have been removing plants of the Datura

genus and other related species from the land surrounding some cities

during the last years[14] However, plants of the Datura genus coexist

with corn crops where the plants have found the optimal medium

for living Therefore, the distribution of these plants increases year by

year[15]

Due to the increasing use of the drug, analytical methods for its

determination are required A difﬁculty is the rapid elimination of

sco-polamine from the body, which precludes the detection of its presence

in the organism after 24 h[3] Moreover, the victims usually do not

report the assaults out of shame, or complain too late, when the

drug has already been eliminated from the organism Then, it becomes

necessary to analyze the evidence used to administer the drug A

va-riety of techniques have been used for the analysis of samples with

scopolamine, such as gas chromatography[16,17]and high

perfor-mance liquid chromatography [18–29] Most of these studies have

been focused on the determination of scopolamine in plant material

[16,17,25,28,29] Scopolamine has also been determined in serum

and plasma[18,19,27] and other biological samples, such as urine

[22]or hair[21,26] Additionally, scopolamine has been determined

in pharmaceuticals[20,23,24]

Capillary electrophoresis (CE) has also been used for the

determina-tion of scopolamine in plant samples[1,29–37]and in pharmaceutical

compositions [2,38] Different methods have been devised for the

simultaneous determination of scopolamine and related compounds

For example, atropine and scopolamine have been separated in Datura

metel L samples[34] Scopolamine and atropine derivatives have been

separated in pharmaceutical formulations[38] With regard to their

use as drugs, scopolamine can exist together with atropine in certain

specimens and so the availability of methods allowing their

separa-tion is cardinal since both substances show different properties

Among other differences, scopolamine is much more likely to

pro-duce sedation and amnesia than atropine Therefore, both substances

could, in principle, be used for different purposes and, accordingly,

their simultaneous determination in samples in which scopolamine

and atropine are present is necessary, and easily possible by CE due

to its high separation power For CE separations of these compounds,

a variety of detection methods have been employed, such as time

ofﬂight-mass spectrometry and ion trap-mass spectrometry[33],

electrochemiluminescence [1,30,37], electrochemistry [1], and DAD

or UV detectors[2,31,32,34–36,38]

However, the sensitivity in absorbance measurements is restricted

by a short optical pathlength Moreover, some species such as inorganic

anions, metal ions, and non-aromatic organic compounds, can only be

determined by indirect UV-detection, a detection approach which is

relatively insensitive and has a limited linear range[39] Capacitively

coupled contactless conductivity detection (C4D) is a sensitive and

uni-versal tool in CE, which has been widely used in recent years for many

applications (see, for example, the following review articles[39–41])

C4D detectors are small, cheap, lightweight, and consume only little

electrical power Since the electrodes are not in contact with the

solu-tion inside the capillary, they do not corrode and, moreover, for this

rea-son the placement of the capillary is easy and removal of the polyimide

coating is not required

The aim of this work was the development of a CE-C4D method for

the rapid analysis of samples suspicious to contain scopolamine A

por-table CE (P-CE) instrument was used and a special effort was made for

the development of simple sample pre-treatments, in order to make

possible the fast analysis of suspicious samples

2 Materials and methods 2.1 Reagents and samples All chemicals used were of analytical grade Tris(hydroxymethyl) aminomethane (Tris), 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), sodium hydroxide (NaOH), atropine and scopolamine hydrobromide were obtained from Sigma-Aldrich (St Louis, MO, USA) Methanol was from Scharlau (Barcelona, Spain) Ultrapure water was obtained from a Millipore Milli-Q water system (Bedford, MA, USA) Soft drink and alcoholic beverages, as well as a moisturizing cream, were purchased in a local supermarket Samples of D stramonium

L were collected in San Andrés del Congosto (Guadalajara, Spain) in mid-January and stored at room temperature

2.2 Instrumentation and experimental procedure

CE experiments were performed on a purpose-built P-CE The P-CE was previously described by Sáiz et al.[42] The instrument wasﬁtted with a contactless conductivity detector (eDAQ, Deninstone East, NSW, Australia) The detector was modiﬁed to work at 12 V with the batteries

of the P-CE The detector excitation frequency was set to 1200 kHz and the amplitude to 100%

Bare fused silica capillaries of 50μm I.D and 365 μm O.D (Polymicro Technologies, Phoenix, AZ, USA) with a total length of 80 cm and an effective length of 65 cm were employed New capillaries were condi-tioned byﬂushing with 1 M NaOH for 40 min, water for 5 min, and running buffer for 30 min The running buffers consisted of 10 mM HEPES/Tris at different pH values between 7.2 and 7.6 and were pre-pared daily The pH-values were determined with a pH-meter (Crison GPL-21, Crison Instruments, Barcelona, Spain) Optimized conditions were achieved when the buffer at pH 7.6 was used The injection was carried out by sample splitting in the interface for 3 s and the separa-tions were carried out by applying−25 kV at the outlet of the capillary After each analysis, the capillary was rinsed with the running buffer for 4 min to maintain the reproducibility of the analyses When a new buffer was used, the capillary was rinsed with water for 5 min and then with the running buffer for 5 min

2.3 Evidence preparation Stock solutions of 1 mg/mL of atropine and scopolamine were pre-pared in methanol For the qualitative determination of scopolamine and atropine, the samples were spiked with standards

2.3.1 Infusion specimen Fresh seeds of D stramonium L were homogenized in a domestic grinder 1 g (fresh weight) of the homogenate was added to 50 mL of water and heated on a hot plate until it begins to boil After cooling down, the infusion wasﬁltered by gravity through a Whatman ﬁlter grade GF/A (1.6μm) in a conical funnel Samples were then directly injected into the P-CE system without dilution

2.3.2 Moisturizing cream specimen Samples were prepared by dissolving 5 mg of scopolamine (MW 438.31) in 500μL of methanol employing a vortex mixer The solution was added to 5 g of the moisturizing cream in a polypropylene tube, which was vortex-mixed for 2 min The extraction of scopolamine from the spiked moisturizing cream was carried out by adding 5 mL of methanol to 5 g of the moisturizing cream evidence The mixture was vortex-mixed for 2 min and then centrifuged for 10 min at 4000 g After centrifugation, three phases were clearly visible and the middle liquid phase was recovered by puncturing the tube with a syringe Finally, the sample was diluted 10-fold (v/v) in water and injected in the P-CE system withoutﬁltration

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2.3.3 Beverage specimens

The beverages studied were prepared using 1/3 (v/v) of alcoholic

drink and 2/3 (v/v) of soft drink because these proportions are usually

utilized in mixed alcoholic beverages The beverages prepared were

the following: whisky with cola, rum with cola, rum with lemon, gin

with tonic water, vodka with tonic water, and vodka with lemon The

total volume of the drink was considered to be 150 mL Scopolamine

was added to the beverages in a concentration of 1.3 mM Then,

samples were vortex-mixed for 2 min, diluted 5-fold (v/v) in water,

and injected into the P-CE system withoutﬁltration

2.4 Data treatment

The electropherograms were processed in Origin (OriginLab

Corpo-ration, USA) Limits of detection (LODs) were estimated as three times

the signal to noise ratio in the electropherograms obtained for the

spiked beverages and the moisturizing cream The noise value was

mea-sured as the maximum deviation of the baseline around the migration

time of the analyte signal Corrected peak areas were calculated by

dividing the peak area by the migration time of the corresponding

peak to correct for the area deviation produced when peaks are delayed

depending on the sample

3 Results and discussion

Theﬁrst aim was to develop sample pre-treatments that can be

readily and quickly carried out Then the separation conditions were

optimized in order to obtain a fast complete baseline separation of

atropine and scopolamine Next, both compounds were determined

in an infusion prepared with D stramonium L seeds, normally used

for recreational purposes Finally, two types of spiked samples for

evi-dence specimens (a moisturizing cream and six commonly consumed

beverages), used for predatory purposes, were also analyzed

3.1 Preparation of the specimens

3.1.1 Infusion specimen

Nowadays, plenty of information can be found in certain Internet

forums on the preparation of scopolamine infusions from some plants

[10,11] These drinks have increasing popularity for their recreational

use According to the information retrieved from the Internet forums,

an infusion of seeds was prepared Seeds of D stramonium L were

ho-mogenized and directly boiled to prepare the infusion

3.1.2 Moisturizing cream specimen

The possibility of administering scopolamine by dermal contact

is well known Novartis™ is marketing Transderm Scōp® patches for

people who are suffering from motion sickness These patches contain

1.5 mg of scopolamine and are designed to deliver in vivo

approximate-ly 1.0 mg of scopolamine over 3 days[43] Considering that this is a

therapeutic dosage, a concentration of approximately 1 mg/mL of

sco-polamine was added to the moisturizing cream (5 mg of scosco-polamine

to 5 g of moisturizing cream) This dose can be used for predatory

pur-poses, as it is a higher dose compared to that in the Transderm Scōp®

patches

3.1.3 Beverage specimens

The beverages studied were chosen for being commonly consumed

in night clubs The amount of scopolamine added to the beverages

was chosen considering the available data about lethal and active

dosages of scopolamine As an example, the ingestion of 10 mg has

been reported to be lethal in children, whereas adults survived more

than 100 mg of scopolamine[44–46] However, exact data on lethal

and active doses of scopolamine are lacking[44,47] For this reason,

a concentration of 1.3 mM of scopolamine (MW 438.31), representing

a total amount of 85.5 mg in 150 mL of drink, was chosen for the

preparation of the beverage samples This concentration was chosen because high concentrations of scopolamine are required to induce the symptoms of amnesia, sedation, and loss of free will without risk

of death

3.2 Selection of evidence treatment When dealing with complex samples, it is important to rely on treat-ment procedures which allow the recovery of the majority of the analyte

in the shortest time possible, without many steps in the procedure This prevents contamination of samples and allows for quick results For this reason, evidence treatments as fast and simple as possible were designed The infusion sample wasfiltered by gravity through a membranefilter in a conical funnel and then directly injected into the P-CE system This step does not require specific instrumentation, such

as vacuumﬁlters, and was carried out manually within 2 min Beverage samples were simply diluted 5-fold because of the high concentration of scopolamine in the drinks and no further sample treatment was needed before the analysis This sample treatment was carried out within 1 min

In the case of the moisturizing cream sample further treatment was needed due to the complexity of the evidence item, which was viscous and non-aqueous However, an easy step of centrifugation with metha-nol followed by a 10-fold dilution in water of the middle phase was enough to detect the scopolamine contained in the moisturizing cream and to have a clean sample that can be injected into the P-CE The whole pre-treatment process for the moisturizing cream was accom-plished in less than 15 min

Therefore, the time needed for the treatment of the infusion and the beverage specimens was insigniﬁcant The moisturizing cream needed more time to be treated, but considering the complexity of the sample, the time spent was reasonably short

3.3 Optimization of the separation conditions Atropine and scopolamine are two tropane alkaloids present in Solanaceous plants Both tropanes have very similar structures (Fig 1)

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Hence their electrophoretic separation could be difﬁcult at certain pH

values However, the separation of scopolamine and atropine is

impor-tant in evidence in which both compounds are present, such as plant

samples The pKa-values of atropine and scopolamine are 9.8 and 7.6,

respectively Therefore, a pH close to the pKa-value of scopolamine

is expected to allow separation of atropine and scopolamine because

atropine then has a higher net charge and should therefore migrate

faster than scopolamine Then, the main consideration for the selection

of a suitable running buffer in this work was based on the ionic

char-acteristics of the basic analytes studied (Fig 1) and the conductivity

of the buffer and the analytes Buffers of low conductivity must be

chosen for conductivity detection to minimize Joule heating whereas

buffers with very high conductivities result in baseline instabilities In

this work, buffers consisting of HEPES/Tris at pH 7.6 were prepared

as background electrolytes at three different concentrations (10, 15,

and 20 mM) As expected, higher concentrations led to larger peaks,

but also to higher noise levels on the baseline Finally, the buffer

consisting of 10 mM HEPES/Tris was chosen for showing the best

signal-to-noise ratio A capillary with a total length of 80 cm and

65 cm to the detector was needed to achieve the initial separation of

atropine and scopolamine When shorter capillaries were used, a single

peak was observed Then, three pH-values close to the pKa of

scopol-amine, namely 7.2, 7.4, and 7.6 were studied The electropherograms

for a mixture of 100μM of scopolamine and 100 μM of atropine

using the three above-mentioned buffers are shown inFig 2 At the

working pH-values, scopolamine and atropine have a low charge and

their equivalent conductivities are lower than the conductivity of the

running buffers Note that for this reason, the detector signals have

been inverted in this work in order to show the positive peaks for

scopolamine and atropine As expected, scopolamine migrated after

atropine and the detection of both compounds at the three selected

pH-values was possible InFig 2it can also be observed that, when

the pH-values were increased from 7.2 to 7.6, scopolamine was losing

its net charge and getting closer to the peak attributed to the EOF

sig-nal migrating after the scopolamine peak The buffer at pH 7.6 allowed

the complete baseline separation of scopolamine from atropine More-over, at this pH the scopolamine peak did not overlap with the peak attributed to the EOF signal On the other hand, although the concen-trations of scopolamine and atropine were the same, there were differ-ences in their peak heights This is due to the different net charges and limiting equivalent conductivities of the analytes, which are lower for scopolamine at the given pH-values For this reason, the peak of sco-polamine was higher than the peak of atropine Also, the peak heights

of scopolamine and atropine increased with the pH-value of the buffer because scopolamine and atropine have lower limiting equivalent con-ductivities at pH 7.6 than at pH 7.4 or 7.2 Therefore, C4D was shown

as a very good alternative to UV detection for the detection of atropine and scopolamine at the working conditions, since the increase of the

pH value allowed not only the obtainment of the baseline separation

of atropine and scopolamine, but also the increase in the detection sen-sitivity for both analytes

Finally, the buffer at pH 7.6 was chosen as it allowed the baseline separation of scopolamine and atropine and showed the highest signal-to-noise ratio for scopolamine The strong electro-osmotic (EOF) ﬂow created at the working pH allowed the determination of scopol-amine and atropine within only 3.5 min

3.4 Evidence analysis Prior to the application of the developed method to the evidence analysis, its analytical performance in terms of LODs and precision, mea-sured as repeatability and reproducibility, was studied The LODs for scopolamine were calculated to be 2.6μg/mL in beverages and approx-imately 0.6μg/mg of cream in the moisturizing cream sample A repeat-ability test of 10 consecutive beverage injections provided RSD values

of 1.8% for migration times and 6.5% for corrected peak areas The inter-day reproducibility for the same samples during 3 different days gave RSD values of 3.3% (n = 18, 3–10 injections per day) for migration times and 15.0% (n = 18, 3–10 injections per day) for corrected peak areas

First, an infusion of seeds of D stramonium L was analyzed because

it may be consumed for recreational purposes Then a moisturizing cream and 6 different alcoholic beverages, all spiked with commercially available scopolamine, were also analyzed These evidential items were chosen for being commonly used for the administration of the drug for predatory purposes

Fig 3 shows the electropherogram for an infusion of seeds of

D stramonium L In this evidence, atropine and scopolamine peaks were detected, as positive peaks as expected, for showing lower conductivity than the baseline A group of fast compounds having higher conductivities than the baseline migrated before atropine and scopolamine Therefore they are shown as negative peaks After sco-polamine, a large positive peak migrated, which was attributed to the EOF In this case, changes in the migration times of scopolamine and atropine, compared with those shown inFig 2, were attributed

to the changes in mobility caused by the sample matrix because direct injection of the sample was performed without any dilution or puri ﬁ-cation However, since scopolamine and atropine were the only posi-tive peaks, despite the large peak attributed to the EOF, they were clearly detected in the electropherogram

The electropherogram for the moisturizing cream spiked with sco-polamine is shown inFig 4 As in the previous case, scopolamine is shown as a characteristic positive peak between the group of negative peaks belonging to the sample matrix and the large peak attributed

to the EOF signal In this case, a good resolution of scopolamine from other peaks was achieved, making possible its determination The electropherograms for the six spiked alcoholic beverages ana-lyzed are depicted inFig 5 All beverage samples showed similar elec-tropherograms and the scopolamine peak migrated after the sample matrix peaks and before the peak attributed to the EOF Once again, sco-polamine was detected in all the samples as a very distinctive peak,

Fig 2 Electropherogram for a standard mixture of 100 μM of scopolamine and atropine in

(a) 10 mM HEPES/Tris pH 7.2; (b) 10 mM HEPES/Tris pH 7.4; and (c) 10 mM HEPES/Tris

pH 7.6 CE conditions: capillary length, 80 cm (65 cm to the detector); applied voltage,

−25 kV; hydrodynamic injection for 3 s; pressure in the system set at 1.5 bar SCO,

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since it was the only positive peak besides the large peak attributed to

the EOF

As can be seen inFigs 3, 4, and 5, the method has been proved

to be highly selective for scopolamine and atropine due to the

charac-teristic peaks shown in the electropherograms The determination of

both tropane alkaloids was fast in all the evidential items analyzed

This, together with the rapid evidence treatments, allowed a very

fast analysis of samples Moreover, the employment of a P-CE may

shorten even more the obtaining of results, since sample preservation

and transportation are not required and the data are immediately

available

4 Conclusions Nowadays, scopolamine has become a drug of increasing use in Europe, and several ways of administration and consumption have been conceived In this work, a P-CE method for the rapid screening of evidence with scopolamine was devised A HEPES/Tris buffer at pH 7.6 allowed the baseline separation of atropine and scopolamine within 3.5 min, being able to distinguish both compounds in those evidential items in which they coexist Moreover, this buffer provided a more sen-sitive C4D detection than the other buffers investigated The studied evidential items containing scopolamine were chosen because they are commonly used for recreational or predatory purposes (an infusion

of seeds of D stramonium L., a moisturizing cream and 6 alcoholic beverages, the last two having been spiked with scopolamine) The sample pre-treatment methods were easy and allowed fast evidence analysis C4D has been proven to be an excellent tool for the detection

of atropine and scopolamine in the samples analyzed, under the exper-imental conditions, as they were always shown as highly characteristic peaks in the electropherograms, allowing the detection of down to 0.6μg/mg of scopolamine in creams and 2.6 μg/mL in beverages There-fore, the method can be used for the fast analysis of evidential items in the search for scopolamine

Acknowledgments

J Sáiz thanks the Ministry of Science and Innovation for his contract associated to the project CTQ2008-00633-E The authors thank Alfonso Vega for his contribution to this work

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Fig 4 Electropherogram for the extract of the moisturizing cream spiked with

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Fig 5 Electropherograms for alcoholic beverages spiked with 1.3 mM of scopolamine (a) Whisky with cola, (b) rum with cola, (c) rum with lemon, (d) vodka with lemon, (e) vodka with tonic water, and (f) gin with tonic water CE conditions: buffer, 10 mM HEPES/Tris pH 7.6; samples diluted 5-fold in water Other electrophoretic conditions as

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