Transcript Profiling of Illicit Diazepam Tablets for Drug Intelligence Purposes

R-LINCS
Valium is killing Scotland’s
Drug taking Poor
“Jack explains that there's an anagram hidden in the word methadone: "the
mad one". We both laugh. Then we search for anagrams in the word
Valium, but there are none. After methadone, Valium is the drug that is
killing Scotland, contributing to, or responsible for 32% of drug-related
deaths in 2011”.
William Nicoll, Photos: Harrison Reid Mar 14 2013
Diazepam is killing Scotland’s
Drug-Taking Poor
When Valium – or diazepam, as it's technically called in Scotland – turned
40, drugs manufacturer Hoffmann La Roche held a celebration where they
unfurled a banner that read: "Thanks for the happiness and relaxation you
have given us over the years.“
Thanks to “Mother’s Little Helper" and the majority of late 20th century
American fiction, many of us have been left with the mistaken belief that
Valium is the preserve of the clinically bored, middle-aged housewife,
when really the drug is killing Scotland's poorest men – detected in the
bodies of 72% of all victims of drug-related death.
Jack can attest to Valium’s power; he's been addicted to the drug for 19
years and had taken 28 pills before meeting me. While he concedes
that they were "whites" (the lower strength two milligram
tablets, as opposed to the stronger "blues"), that amount is still
more than nine times the effective daily dose for anxiety.
William Nicoll, Photos: Harrison Reid Mar 14 2013
Background
• Started with diazepam analysis for student
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projects in 2012
Police Scotland – Kenny Simpson
Discussions with Isobel Stewart
Required to get Crown Office permission to use
tablets from closed cases
It was thought that this work could be expanded
to provide drug intelligence information
Awarded R-LINCS (Research-Led Innovative
Nodes for Contemporary Society) PhD studentship
from Abertay
Began collaboration on the project with Police
Scotland and RGU in September 2013
Background
Aims of the R-LINCS Project:
To provide drug intelligence information
that could assist the police in determining links
between different seizures. This will be
attempted through the measurement of certain
physical and chemical characteristics of
illicit tablets and the extraction of
information from the data set to construct
a statistical model to identify different
populations.
Scoping exercise
 Photography
 Tablet Weight and Measurements
 Diazepam quantification through HPLC (+RGU)
 DSC (RGU)
 Thermal Gravimetric Analysis (RGU)
 Scanning Electron Microscopy (RGU)
 GC-MS for the identification of active drug substances
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

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
(+RGU)
Energy Dispersive X-Ray Analysis (RGU)
Adulterants (+RGU)
Identification of colourants
Quantification of sugar – lactose??
Tabletting (RGU)
Initial selected Parameters
 Photography
 Tablet Weight and Measurements
 Diazepam quantification through HPLC
 GC-MS for the identification of active drug
substances
 [Analysis of Dyes through UV-Vis]
 [Analysis of Sugars through HPLC]
Photography
Images recorded using an Olympus DSX100 microscope on loan from Olympus
Diazepam Analysis
From a total of 1715 tablets analysed:
Analytical Results of All Cases Received (54)
• 67% Diazepam Drug Substance
• 33% “Other” Drug Substances
Analytical Results of Cases from 2013 (11)
• 27% Diazepam Drug Substance
• 73% Other Drug Substances
 Diazepam Quantification from All Cases
Received
• Only 32% contain 10mg of Diazepam
• Highest recorded diazepam content = 48mg
Benzodiazepines
Diazepam
First marketed
as Valium by
Hoffmann-La-Roche is
the archetypical
benzodiazepine drug
used to treat anxiety,
panic attacks insomnia
and seizures
Phenazepam
No methyl on
Nitrogen and a
bromine in place
of the chlorine
and extra chlorine
in the non-fused
phenyl ring.
Etizolam
Benzene ring has
been replaced by
a thiophene ring,
making the drug
a thienodiazepine.
It is also a fused
triazole
Plus other non-benzodiazepines
The Database
 Tablet Weights
 Imprint Details
 Identification and Quantification of Main Drug
Substance
 Identification of Dyes
 Identification of Main Excipients
 Used to Build A Statistical Model
The Database
 The database requires constant updating as further results are
produced.
 This will create an easily accessible tool for comparison and
analysis of data.
 In addition, the use of statistical techniques should help with
the visual interpretation and understanding of the results.
 At present the statistical analysis on the weight of the tablets
has been utilised
 Early work using ‘Miner 3D’ produces an interesting and useful
way to visualise the results.
Grouping of tablets using
Miner 3D
Contain
greater than
20 mg
diazepam
Possibly
pharmaceutical
grade
Do not contain
diazepam
Ave. of Weight
Diazepam content
Illicitly
manufactured
tablets having
10 mg
Std. Dev of Weight
Results so far
Genuine tablets (red) and Probably genuine
Counterfeit tablets


Variability in Level of Diazepam
Different Active Drug Substances
Potential Diverted Pharmaceutical Tablets

Tablet Mass
The Future

Dyes

Sugars

More Statistical
modelling
The Further Future
ECSTACY
The Collaboration
• Kenny Simpson (Police Scotland)
• David Bremner (AU)
• Kevin Farrugia (AU)
• Mae MacDougall-Heasman (AU)
• Anne Savage (AU)
• Isobel Stewart (AU)
• Graham Wightman (AU)
• Kerr Matthews (RGU)
• Raymond Reid (RGU)
• Ann Tough (RGU)
• Stuart Waddell (RGU)