Transcript Herbal Medicines?: A Case Study

Detection of the pharmaceutical agent ‘Glaucine’ as a recreational drug
Analytical Unit St Georges - University of London, London,
2
Guy’s and St Thomas’ Poisons Unit, London, UK
1
UK
Jennifer BUTTON1, Paul I DARGAN2, Leonard HAWKINS2, Hanna OVASKA2, Satnam LIDDER2, John RAMSEY1, David M WOOD2, David W HOLT1
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INTRODUCTION
EXPERIMENTAL
RESULTS
Glaucine is an anti-tussive agent, which is used therapeutically in several
countries in the European Union, such as Romania and Bulgaria, as well as
neighbouring countries, including Iceland and Russia. Therapeutic use of
glaucine has been reported to be associated with dissociative type
symptoms [1].
Animal studies suggest that glaucine has central
dopaminergic effects [1,2]. Glaucine is a marketed pharmaceutical; this is
the first reported case of confirmed toxicity associated with its recreational
use.
Materials
Glaucine (Glauvent) was obtained in tablet form (40mg) from Sopharma,
Bulgaria. Flurazepam, obtained from Sigma-Aldrich (Poole, Dorset,
England), was used as an internal standard (IS). Sodium hydroxide (40%
solution) and phosphoric acid were also obtained from BDH. HPLC grade
methyl-tert-butyl-ether (MTBE) was purchased from Rathburn Chemicals
Limited (Walkerburn, Scotland).
Glaucine and flurazepam were quantified monitoring their most abundant
ion m/z: 354 and 86 and their retention times were 19.09 and 17.75 minutes,
respectively.
Case Study
A 23 year old female presented to the emergency department (ED) following
ingestion of two tablets of ‘Head Candy’, a 1-benzylpiperazine (BZP) free
‘herbal high’, marketed as a legal alternative to conventional recreational
drugs of abuse such as MDMA (‘ecstasy’) and amfetamine, which had been
purchased from a local ‘head shop’. She developed nausea and vomiting
within 30 minutes of ingestion, followed by a period of ‘dissociative type
symptoms’, feeling detached and ‘in another world’. On arrival in the ED she
was agitated, vomiting, tachycardic (100 bpm) and tachyphnoeic, but with a
normal blood pressure (135/82 mmHg) and temperature (36.8C). Her
pupils were dilated (6mm), although the remainder of her neurological
examination was normal. Abdominal examination was unremarkable. She
was treated with intravenous fluids and anti-emetics (prochlorperazine
12.5mg IM and cyclizine 50mg IV) and admitted overnight for observation.
She was discharged the following day once her symptoms had resolved.
Figure 1. London Underground Mind Music Red Eye Frog, BZP Free,
Herbal High ‘Party Pill’ containing Glaucine only. TICTAC Communications Ltd
Samples collected at the time of admission, were sent to the Forensic
Toxicology Service, St George’s, University of London for analysis. Glaucine
was detected in both the urine and serum (approximately 0.7mg/L*)
samples. There are no previously published therapeutic or toxic
concentrations for comparison. Extended toxicological screening did not
detect any other drugs or ethanol, except for cyclizine that was administered
in the ED.
*Due to the unavailability of a pure reference standard, Glaucine was obtained in tablet
formation for confirmation and quantification. The measured concentration should
therefore only be considered an approximation.
Figure 3. NIST Library Ion Spectra for Glaucine.
(a)
(b)
Figure 2. 40mg Glaucine (Glauvent) Sopharma, Bulgaria. TICTAC Communications Ltd
Sample preparation
The sample and calibrators (250µL) were prepared using liquid-liquid
extraction. They were adjusted to an alkaline pH with 1M sodium hydroxide
(250µL), after the addition of 100µL of the IS flurazepam (1mg/L). The
solution was extracted with 4mL MTBE. Following centrifugation the organic
layer was transferred to 0.1M phosphoric acid (250µL) and mixed. After
phase separation by centrifugation the organic layer was removed to waste.
1M sodium hydroxide (100µL) and MTBE (200µL) were added to the
remaining subnatent. The samples were then vortex mixed (30 seconds)
and centrifuged. An aliquot of the supernatant was injected onto the GC-MS
system.
Gas chromatography-mass spectrometry
GC-MS analysis was performed using a Shimadzu GC-MS-QP2010 with a
Shimadzu AOC-20i autosampler. An HP-5 MS (30m x 0.25mm, 0.5µm; 5%Phenyl)-methylpolysiloxane) analytical column (Agilent, Palo Alto,
California), was employed for separation. Helium was used as the carrier
gas at a flow rate of 1mL per minute.
The injection volume was 1.0µL and injections were made in splitless mode.
The injector was maintained at 225°C and the detector at 200°C. The initial
column temperature was set at 80°C and held for 4 minutes. It was then
ramped by 25°C per minute up to 290°C and held for 9.6 minutes, giving a
total run time of 22 minutes. Positive Electron Impact Ionisation (EI) mode
was used and data were collected using single ion monitoring (SIM).
Figure 4. (a) Chromatogram (b) Calibration curve, quadratic curve fit applied
CONCLUSION
Glaucine is a marketed pharmaceutical; this is the first reported case of
confirmed toxicity associated with its recreational use. In addition this case
highlights that it is being included by manufacturers in legally sold ‘BZP-free’
alternatives to established recreational drugs. In our view legislative
authorities should be aware of the potential diversion of this pharmaceutical
into the recreational drug scene, and adapt the licensing of this product.
References:
[1] Rovinskia VI. (2006) Acute glaucine syndrome in the physician's practice: the
clinical picture and potential danger. Klin Med (Mosk) 84:68-70
[2] Asencio M Hurtado-Guzmán C, López JJ, et al. (2005) Structure-affinity
relationships of halogenated predicentrine and glaucine derivatives at D1 and
D2 dopaminergic receptors: halogenation and D1 receptor selectivity. Bioorg
Med Chem 13:3699-3704