Drug Charc & Impurity Profile

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Printed in Austria United Nations publication

V.01-83778May 2001650 Sales No. E.01.XI.10


ISBN 92-1-148139-2
ST/NAR/32/Rev.1
UNITED NATIONS
INTERNATIONAL DRUG CONTROL
PROGRAMME
DRUG
CHARACTERIZATION/
IMPURITY PROFILING
Background and Concepts
MANUAL FOR USE BY NATIONAL
LAW ENFORCEMENT AUTHORITIES AND
DRUG TESTING LABORATORIES
United Nations Office
for Drug Control
and Crime Prevention
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UNITED NATIONS INTERNATIONAL DRUG CONTROL PROGRAMME
Vienna
DRUG
CHARACTERIZATION/
IMPURITY PROFILING
Background and Concepts
MANUAL FOR USE BY NATIONAL
LAW ENFORCEMENT AUTHORITIES
AND DRUG TESTING LABORATORIES
Scientific Section
United Nations
New York, 2001
01-83778_pre.p65 23/01/2004, 11:11 1
ST/NAR/32/Rev.1
UNITED NATIONS PUBLICATION
Sales No. E.01.XI.10
ISBN: 92-1-148139-2
01-83778_pre.p65 23/01/2004, 11:11 2
iii
PURPOSE AND USE OF THE MANUAL
Worldwide, characterization/impurity profiling of seized drugs is increasingly
viewed as a valuable complement to routine law enforcement investigative work,
adding valuable, scientific information in support of law enforcement intelligence
gathering and operational work. In principle, and provided the existence of an
adequate institutional framework and close cooperation between the different
authorities, drug characterization/impurity profiling studies can help to answer a
wide variety of questions ranging from dealer-user relationships, drug source, distri-
bution networks, and trafficking routes to manufacturing methods and precursors
used. Some of that information may also be used by regulatory authorities, for
example, to identify precursors and other chemicals for control.
In practice, however, there is frequently a discrepancy between the enthusiasm for
setting up characterization/profiling programmes and the expectations associated
with such programmes on the one hand, and the acknowledgment of individual roles
and responsibilities and the operational use of their results on the other.
The present manual is intended to fill this gap by providing an introduction not only
to the concept and operational value of characterization/profiling, but also to its
limitations. The manual is mainly aimed at law enforcement and laboratory person-
nel intending to set up operational programmes for drug characterization/impurity
profiling.
Subsequent manuals will deal with individual drugs and the chemical analytical
approach to their characterization/impurity profiling. The present manual, and other
manuals, dealing with the identification and analysis of various groups of drugs
under international control can be requested from UNDCPs Scientific Section (see
address below).
UNDCPs Scientific Section would welcome observations on the contents and use-
fulness of the present manual. Comments and suggestions may be addressed to:
Scientific Section
Policy Development and Analysis Branch
Division for Operations and Analysis
United Nations International Drug Control Programme
Vienna International Centre, VIC
P.O. Box 500
A-1400 Vienna
Austria
Fax: +43-1-26060-5967
e-mail: Lab@undcp.org
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v
CONTENTS
Paragraphs Page
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-4 1
II. Drug characterization studies: possible information . . . . . . . . . . . . . . 5-9 2
II. Operational value of drug characterization studies for law enforcement
investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10-23 3
A. Establishing specific links between two or more samples . . . . . . . 14-15 3
B. Establishing drug distribution patterns . . . . . . . . . . . . . . . . . . . . . . 16-18 4
C. Identifying the source of drug samples . . . . . . . . . . . . . . . . . . . . . . 19-21 5
D. Monitoring methods used for clandestine drug manufacture . . . . . 22 5
Annex
SCIENTIFIC/TECHNICAL BACKGROUND TO DRUG
CHARACTERIZATION/IMPURITY PROFILING STUDIES . . . . . . 1-39 6
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 6
2. Sources of information for drug profiling and characterization . . . . . . . 2-5 6
3. Chemical implications of clandestine drug production and supply . . . . 6-15 7
A. Clandestine drug production . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6-7 7
B. The concept of batch variation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8-13 7
1. Batch variation in natural and semi-synthetic drugs . . . . . . . . 10-11 7
2. Batch variation in synthetic drugs . . . . . . . . . . . . . . . . . . . . . 12-13 8
C. Drug supply . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14-15 8
4. Drug characterization in practice: interpretation of results . . . . . . . . . . . 16-39 9
A. The significance of chemical similarities and differences between
drug samples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16-23 9
B. Establishing specific links between two or more samples . . . . . . . 24-26 11
C. Establishing drug distribution patterns . . . . . . . . . . . . . . . . . . . . . . 27-30 12
D. Identifying the source of drug samples . . . . . . . . . . . . . . . . . . . . . . 31-37 13
1. Natural and semi-synthetic drugs . . . . . . . . . . . . . . . . . . . . . . 33-36 13
2. Synthetic drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 14
E. Identifying and characterizing the specific starting materials
employed in clandestine drug manufacture . . . . . . . . . . . . . . . . . . 38-39 14
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1
Summary
1. Drug characterization studies can provide information useful for drug law en-
forcement authorities. Chemical links between samples can be established, and
material from different seizures can be classified into groups of related samples.
Consequently, and most useful for law enforcement authorities, specific links for
instance between suppliers and users can be established, drug distribution patterns/
networks can be built up, and the source, including the geographic origin of drug
samples may be identified. The exact purpose of any comparative study determines
the analytical approach. The forensic chemist has to take care in interpreting the
results, taking into account peculiarities of different drug types and the implications
of the presence or absence of different types of impurities, namely manufacturing
impurities and cutting agents. Close cooperation between laboratory and law en-
forcement personnel is essential to maximize the operational value of drug charac-
terization studies for law enforcement investigative work.
Introduction
2. Whether plant-based, such as heroin, cocaine or cannabis, or synthetic, such
as the various amphetamines, illicit drugs are normally complex mixtures which
rarely contain the drug alone. As a consequence of the crude clandestine laboratory
conditions under which they are produced, their chemical composition shows large
variability. As well as containing the drug itself, samples may contain one or more
of the three different types of key components:
natural components present in raw materials (e.g., coca leaf, opium) used
for the production of certain plant-based drugs such as cocaine or heroin,
which are co-extracted during drug production, and which are not com-
pletely removed from the final product,
by-products generated during drug manufacture and related to the method
of manufacture, and
cutting agents which may be added at any point in the distribution chain,
subsequent to drug manufacture.
3. Although all samples of the same drug prepared in the same way could be
expected to contain the same impurities (excluding cutting agents which may be
added at any stage in the distribution chain), their relative concentrations may show
large variations. These variations may be attributed to the exact nature of the starting
materials or to the specific method by which the drug has been processed, manufac-
tured, distributed, or stored.
4. Detailed chemical analysis of drug samples enables measurement of the relative
concentrations of major, minor and trace components (with appropriate analytical
methods, complex chemical profiles can thus be obtained with different drug
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2
samples). By such an approach, a characteristic chemical signature can be assigned
to every drug sample. These impurity profiles may contain natural components, by-
products and cutting agents. Examination of all the components of a sample, in
theory, provides a complete history of the sample, and may therefore play a key
role in characterizing samples.
I. Drug characterization studies: possible information
5. Law enforcement authorities often require evidence to link drug dealers and
users; or they may want information on local distribution networks. Forensic labo-
ratories are then asked to determine whether samples of seized drugs are related. By
identifying similarities and differences between drug samples, the information gen-
erated by drug characterization studies can be used to help answer the following
questions:
are two or more drug samples connected?
does this relationship provide a link between, for example, a drug dealer
and a user?
does the relationship between samples provide any useful information relat-
ing to local, national, regional or international drug supply and distribution
networks or any information as to the extent of such networks?
where does the sample come from (e.g., geographic origin, laboratory
source)?
what is the method of clandestine drug production? Which specific chemi-
cals are employed in the manufacturing process ?
6. From an investigative point of view, sample characterization studies can there-
fore be carried out either for evidential or for intelligence purposes. They may thus
be used either to help to confirm a connection between two (or more) samples in,
for example, drug supply cases for prosecution purposes. Or they may be used to
provide more general intelligence information such as the identification of local,
regional or international distribution networks and sources of drug supply, in support
of law enforcement investigations.
7. Depending on the nature of the drug sample investigated, the information gen-
erated through drug characterization studies may be used to identify from where,
how, and to what extent the drug has been distributed. It may be used to provide
background intelligence on the number of sources of drugs, on whether those
sources are within a country or are internationally based, and on points of drug
distribution and drug distribution networks. Information from drug characterization
studies may also be used to estimate how long a particular laboratory has been
operating, and to assess the scale and output of a drug operation.
8. At the national and international levels, examination of samples may provide
valuable information to identify new or established trafficking routes and distribu-
tion patterns. Further, in some cases, the identification of geographic origin (region
or country), and sources of international supply, may be used to estimate what
percentage of the drug reaching a country has come from which of the different drug
producing areas of the world. Drug characterization/impurity profiling may also
assist in the identification of output from new illicit laboratories, and in the moni-
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toring of common methods used for clandestine drug manufacture. This, in turn,
may provide information helpful to the maintenance of other intelligence gathering
tools, for example, precursor monitoring programmes. Finally, drug characterization
studies may provide supportive evidence in cases where a differentiation of illicitly
manufactured drugs from those diverted from legitimate sources is required.
9. The Annex provides some more scientific/technical details and background in-
formation necessary to appreciate both the potential and the limitations of drug
characterization/impurity profiling studies, and the conclusions which can be drawn
from them.
II. Operational value of drug characterization studies
for law enforcement investigations
10. From an investigative point of view, drug characterization/impurity profiling
studies can serve different purposes; in particular, they may help to: (a) establish
specific links between two or more samples; (b) classify material from different
seizures into groups of related samples, thus building up distribution networks; and
(c) identify the source, including the geographic origin, of a drug sample. This
information may be used for evidential purposes, or it may be used as a source of
intelligence to identify samples which have a common history. A fourth purpose of
drug characterization is to monitor clandestine drug production methods, and the
chemicals employed.
11. Drug characterization is a multi-disciplinary collaborative exercise. Maxi-
mum usefulness of drug characterization studies can only be expected if close
collaboration between laboratory personnel, police and customs authorities, and
mutual understanding of the purpose, needs, possibilities and limitations of drug
characterization/impurity profiling studies, are ensured. Since the specific aim
of any comparative study determines the analytical approach, there is thus the
implicit need for law enforcement personnel to be clear in specifying the infor-
mation they expect from the forensic scientist.
12. It is also important to recognize that drug impurity profiling is not a routine
analytical technique. In order to allow more insight into a seized drug sample than
by normal chemical analysis, and to identify any links between two or more seized
drug samples, experienced chemists and dedicated equipment are required. More-
over, any drug characterization/impurity profiling programme must be ongoing to
build appropriate databases of results for interpretative purposes.
13. The practical value of drug characterization/impurity profiling studies for rou-
tine law enforcement investigative work in the four different areas outlined above
can be summarized as follows:
A. Establishing specific links between two or more samples
14. Attempts to link samples are aimed at establishing a connection between the
samples. Ultimately, that information may be used by law enforcement to establish
links between different individuals from whom those samples were seized. Links
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between samples can be established at various levels, such as source (drug produc-
tion) or the different stages of drug supply. The fact that impurity profiles can be
shown to coincide is of high evidential value, particularly in local distribution cases
such as dealer/user cases. Ultimately, the establishment of a relationship between
two drug samples may have a major impact on charges/penalties for the individuals
involved (e.g., trafficking charge versus possession, etc.).
15. While providing sound scientific facts, however, chemical characterization
studies are only a part of drug comparisons work overall, particularly in cases for
evidential purposes where evidence of links is to be presented in court. Results have
to be complemented by other information about the samples in question, for example
on purity, appearance, packaging, etc, and with information relating to the presence
or absence of cutting agents.
B. Establishing drug distribution patterns
16. It is possible to classify material from different seizures into groups of related
samples. The identification of such groups may provide useful information in rela-
tion to trafficking patterns and distribution networks. Established groups may rep-
resent different laboratories or different drug related organizations. The size of a
group and the time span over which samples falling within the group have been
seized can furnish information on the scale and period of drug operations. Chemical
comparisons of clandestine drugs are particularly useful for the investigation of
small-scale or local drug supply networks. Such information is, in turn, of value in
relation to the confiscation of financial assets.
17. For natural and semi-synthetic drugs, such as cocaine, heroin or cannabis, the
establishment of distribution patterns and networks is not easy. This is largely the
consequence of the nature of clandestine production processes of such drugs, namely
the absence of distinct production batches (see Annex for further details). More-
over, the nature of international trafficking in natural and semi-synthetic drugs is
frequently such that the product of a laboratory operation at any given time (batch)
may be distributed in different supply chains, to a variety of destinations. As a
consequence, the use of laboratory resources for chemical comparison of such sam-
ples would appear to be an ineffective approach to drug law enforcement; it would
be unrealistic to expect a collation of regional or even international results from a
single batch of drug in such a way that enforcement agencies could act positively
on the information. Chemical comparison of such samples may thus not help to
target major trafficking organizations, since a sufficiently large information base
could probably never be developed to allow identification of related seizures in large
networks.
18. In the case of synthetic drugs such as amphetamines, by contrast, large groups
of related samples can be identified, both nationally and internationally (see Annex
for further details). This is of value in that it lends drug enforcement agencies both
the time and the opportunity to investigate and then follow up background informa-
tion associated with a series of related drug seizures. Good intelligence about major
dealers in an operation may thus be obtained, and major centres of drug supply may
be identified. While this is certainly realistic on a national basis, with improved
cooperation between forensic chemists and law enforcement personnel across bor-
ders, the approach may also be possible on a regional and even international basis.
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C. Identifying the source of drug samples
19. The main aim of determining the source of a drug sample is to identify its
geographic origin, the clandestine drug production unit/chemist, or the source of
supply or distribution of the sample.
20. In practice, however, assigning regions/countries of origin to drug samples is
probably only relevant to routine law enforcement investigations in cases of impor-
tation charges. In general, the origin of drugs such as cocaine, heroin and cannabis
is well known (for synthetic drugs, it is in their very nature that the geographic
origin cannot be derived immediately (see Annex)). Moreover, specific knowledge
of the region of origin of a drug would not, necessarily, be of great value in limiting
traffic of a drug into a country; whether heroin, for example, originates in South
West or South East Asia is of little concern to the practical interdiction of the drug
along the supply routes. By contrast, determining the geographic origin of a drug
sample may be useful for international policy initiatives, or in cases where evidence
is sought to identify the exact origin of a sample.
21. As a consequence, identifying the source of supply is mainly used to link drug
samples to specific illicit laboratory operations, and to establish sources of distribu-
tion.
D. Monitoring methods used for clandestine drug manufacture
22. Detailed examination of impurity profiles and identification of impurities may
provide information on the method and conditions of drug synthesis, and of the
chemicals used. Qualitative information thus generated may be a valuable tool to
regulatory authorities, for instance, to identify new targets in precursor monitoring
programmes and to alert to new drug trends. While this is obviously more relevant
for synthetic drugs, with their higher flexibility in the clandestine manufacturing
process, such an approach, routinely used, may also help to identify trends in the use
of solvents and other chemicals for heroin and cocaine processing.
23. Section 4.A in the Annex provides further practical details and scientific/tech-
nical aspects for consideration when carrying out drug characterization/impurity
profiling studies, interpreting the results of such studies, or using them operationally.
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Annex
SCIENTIFIC/TECHNICAL BACKGROUND TO DRUG
CHARACTERIZATION/IMPURITY PROFILING STUDIES
1. Introduction
1. In order to explore the potential of comparative chemical analysis and to appre-
ciate the difficulties in drawing conclusions from such studies, it is necessary to
consider (a) the sources of information available to the forensic chemist for drug
characterization/impurity profiling studies, as well as (b) the implications of the
different stages of drug production and the different stages in the drug supply chain
for the chemical profiles of drug samples.
2. Sources of information for drug profiling and characterization
2. Whether drug characterization work is for evidential or intelligence purposes, it
is advantageous to obtain as much information on a drug sample as possible. The
forensic chemist, in carrying out such characterization/profiling studies, largely re-
lies on two different sources of information, physical and chemical examinations.
3. The most appropriate analytical approach for drug characterization studies de-
pends on the type of sample, i.e., tablets, capsules, powders, liquids and natural
materials (e.g., opium, cannabis products). The most simple type of investigation is
a visual inspection of the physical characteristics of the sample. In many cases
differences/similarities in, for example, the colour, texture or general appearance of
samples can be observed. The forensic chemist, in combining this information with
information from other sources, may be able to draw conclusions on whether or not
two or more drug samples are connected.
4. Valuable information to show that samples may be more directly related can
also be obtained by comparison of their packaging (including materials, the way of
packaging, and the examination of any fingerprints on packaging), and by examina-
tion of any characteristic marks the samples may display. Different seizures of illicit
tablets, for instance, may be linked to a distribution network, a single source of
production, and in some cases to the actual equipment used for tableting, by exami-
nation of the defects or marks on the tablet surfaces.
5. In addition to the examination of physical characteristics, and especially where
these have limited significance, samples can also be characterized by chemical
analysis. The detailed chemical analysis of drug samples by modern analytical tech-
niques assigns to every drug sample a characteristic chemical signature of major,
minor and trace components. Careful examination of these impurity profiles offers
a valuable means of comparing and grouping different seizures.
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3. Chemical implications of clandestine drug production and supply
A. Clandestine drug production
6. In the case of natural and semi-synthetic drugs such as cocaine, heroin and
cannabis products, the geographic origin of the raw materials (e.g. opium or mor-
phine base, coca leaf, etc) and the general procedures used for the extraction, con-
version and/or purification contribute impurities to the final illicit product.
7. Samples of synthetic drugs such as amphetamines may contain various synthetic
impurities consisting of residual traces of chemicals essential to the drug manu-
facturing process and by-products resulting from side-reactions. The presence and
relative concentrations of these impurities are dependent upon the quality of the
starting materials used, the route of synthesis, the reaction conditions, the extent of
purification of the final product(s), and overall, upon the skills of the clandestine
chemist.
B. The concept of batch variation
8. When a drug is manufactured, separate and discrete batches of materials are
usually processed at any one time. Because production conditions may never be
reproduced exactly each time, variations will occur in the impurity content of final
products from the same source, i.e., different batches from the same clandestine
operator or laboratory will have different chemical characteristics (so-called inter-
batch variation). In addition, because illicit products are usually non-homogenous,
differences in impurity content may also be seen across a single batch of drug (so-
called intra-batch variation). Under normal circumstances, it is reasonable to as-
sume that inter-batch variations will be greater than intra-batch variations. However,
it is difficult to say by how much samples should differ in their impurity content
before they can be assumed to have come from different batches or sources.
9. Successful classification of samples is thus only possible if sufficient informa-
tion is generated by the analytical method and if the variation in chemical compo-
sition observed between different batches is greater than that within the same batch.
This means, in turn, that large intra-batch variations may result in a failure to match
samples which are in fact related.
1. Batch variation in natural and semi-synthetic drugs
10. The potential for batch variation is particularly high with natural and semi-
synthetic drugs because of the crude laboratory conditions associated with their
illicit production. In practice, however, little is known about the extent of variation
in the impurity content of samples from within one country or one regional source.
Also, little is known about the size of a single production batch in the processing of
such drugs, or about the extent of inter- and intra-batch variations. Moreover, with
raw materials frequently being added to continuously operating production lines, the
concept of batch processing for natural and semi-synthetic drugs may not mirror the
actual situation.
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11. In practice, the different items of large multi-item seizures of natural drugs
such as heroin and cocaine are often found to be made up of materials with quite
different impurity profiles. This may mean that the intra-batch variation is large or
that the seizure is made up of smaller batches of drug manufactured at different
times (and possibly at different locations). As a consequence, it may be difficult to
link the different items by their impurity profiles had they been seized separately.
Examinations of physical characteristics and/or of the materials used for packaging
the different items may in this case be required to provide sufficient information for
linking the samples.
2. Batch variation in synthetic drugs
12. With synthetic drugs, batches themselves as well as intra-batch variations are
relatively small, such that in most cases there is little difference in impurity content
across a single batch of drug. Samples from a single batch synthesis may therefore
be linked relatively easily. (This is not the case, however, if final products are
packaged while wet, since liquids may differentially separate impurities at the
top or bottom of a package.)
13. Conditions of clandestine manufacture are usually more closely controlled
with synthetic drugs than with natural and semi-synthetic drugs. Inter-batch varia-
tions may thus be sufficiently small so that different batches of a drug may still be
linked by their impurity profiles. Practical experience has confirmed that samples
produced by an established method, though in different batches, in the same illicit
laboratory may be linked by their impurity profiles.
C. Drug supply
14. The drug supply chain is long and complex, consisting of (for the sake of
argument) producer, trafficker, distributor, supplier and user (see figure 1). Once the
drug is processed or manufactured, a drug producer may supply one or more traf-
fickers, a trafficker may supply one or more distributors, a distributor may supply
one or more suppliers, and a supplier may supply one or more drug users. At each
stage of the chain, cutting agents may be added, with the result that the drug sample,
and hence the impurity profiles, will become progressively more complex. The
further away from the source of the sample (whether this is the country or region of
origin, or the illicit laboratory where the drug was manufactured), the greater are the
chances that diluents and adulterants will have been added.
15. Similarly, at the other end of the supply chain, a drug user may obtain his drug
from one or more suppliers, who in turn may obtain drug from one or more distri-
butors. Although in practice probably less likely, the distributor may also obtain
supplies from one or more major traffickers, and the trafficker may obtain his/her
drug from one or more producers. It is therefore clear that samples related by source
(i.e., coming from the same producer) may be distributed in separate chains of
supply.
01-83778_1.p65 23/01/2004, 11:11 8
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4. Drug characterization in practice: interpretation of results
A. The significance of chemical similarities and differences
between drug samples
16. In a drug supply chain consisting of production (source), trafficking, distribu-
tion and supply (see figure 1), the following connections between two or more
samples may exist: (a) samples may be linked by a common history (i.e., they were
produced by the same producer and distributed in the same chain of supply; case 1);
(b) they may be linked by source, but not by their distribution (case 2); and (c) they
may be related by distribution, but they originate from different sources (cases 3 and
4). The chemical implications of these scenarios are detailed below.
17. Where the chemical profiles
1
of samples are indistinguishable (figure 1,
case 1), it is clear that samples are linked by a common history; they contain the
same relative proportions of co-extracted and/or manufacturing impurities, and they
contain the same cutting agents. For powdered drugs this means that the samples
probably come from the same source (and the same batch) and are probably asso-
ciated with the same distribution network; it would be unlikely that the same cutting
agents would have been added to the samples in exactly the same quantities in
different chains of supply.
18. It is important to recognize that a chemical link between the impurity profiles
of two drug samples does not necessarily signify a direct link between the individu-
als associated with those samples; two or more unrelated drug traffickers, for in-
stance, may each have separately imported small portions of a larger single batch.
In the same way, results from drug comparisons work used without input from
intelligence sources and/or additional information on physical properties, can not
prove, for example, that a specific sample in the hands of a drug user came from a
supply of drugs in the possession of a local dealer: two or more local dealers may
each have obtained the same type of drug sample from a single wholesale consign-
ment.
19. In cases where chemical profiles are significantly different, it is clear that there
is no chemical link between the samples. However, there is always the possibility
that the samples may be related (case 4): they may have been sold by a local dealer
who has diluted his drug supply using different cutting agents or who has obtained
his supplies from more than one wholesale source. At the international level, the
samples may represent products from different manufacturers brought together for
final processing and/or distribution as a single consignment.
20. Chemical profiles of samples from a common source may differ if the samples
are seized at different levels in the distribution chain, or if the samples are distributed
in different chains. Cutting agents may be added at different stages of distribution,
and different cutting agents may be added by different dealers. Consequently, sam-
ples will have the same relative proportions of co-extracted and/or manufacturing
impurities but are likely to contain different cutting agents (cases 2a-2c). While such
samples are probably related by source, they are unrelated by distribution and do not
have the same history. Caution should be exercised when interpreting such results,
because chemical profiles may suggest that they are not linked.
1
The chemical profile of a sample is understood to be the profile of the co-extracted and
manufacturing impurities (impurity profile), and the cutting agents.
01-83778_1.p65 23/01/2004, 11:11 9
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01-83778_1.p65 23/01/2004, 11:11 10
11
21. It is also difficult to establish a connection between samples which are shown to
contain similar proportions of the same cutting agents but which differ in the relative
proportions of co-extracted and/or manufacturing impurities (case 3). Consequently,
while the samples are related by distribution, chemical profiles may again suggest that
the samples are not linked. This situation is unlikely at the major distributor level where
wholesalers are likely to obtain supplies from a single source. It is more common at
the local level where a dealer may obtain drugs from a number of sources and then
dilute the different types of sample with the same cutting agents.
22. Practical experience shows that the chemical profiles of samples with the same
history (i.e., samples from the same source and distributed in the same chain) are
often very similar, but rarely indistinguishable. Variability in profiles is generally
related to inter- and intra-batch variations introduced during drug manufacture.
Homogeneity of samples can also be affected by poor mixing or addition of cutting
agents. This, again, makes comparison studies more complex.
23. In many cases, physical inspection of samples (e.g. an examination of punch
marks) can provide additional evidence of direct links between samples. However,
in cases of tableted drugs where drug production and tableting do not necessarily
take place in the same location, similarities in physical characteristics between dif-
ferent tablet seizures simply suggest a relationship at the level of the tableting labo-
ratory, while the drug powders may be from different sources. Conversely, different
physical shapes do not necessarily mean that there is no relationship between two
samples; drug powders manufactured in the same batch may be tableted in different
batches using different moulds or different tableting machines.
B. Establishing specific links between two or more samples
24. Irrespective of the equipment and software available in a laboratory carrying
out profiling studies, the results of such studies have to be interpreted carefully by
an experienced analyst, especially if those results are to be presented in court. A
measure for the validity/quality of the results and the conclusions drawn from them
is the strength of evidence.
25. The strength of evidence of a link between samples, as assessed by examina-
tion of profiles of those samples, is determined by two factors, the closeness of their
correlation and the frequency of the particular pattern of the profile. The strength of
evidence may be increased, if it can be shown that the pattern of the particular
profiles is of an unusual type, i.e., of low frequency, compared to the patterns of
previously analysed samples. The strength of evidence may also be increased by an
assessment of how common or unusual various individual components are. For
example, the presence of unusual cutting agents may provide a critical source of
information to help compare and link samples, and provide evidence of direct (im-
mediate) links in conspiracy or dealer/user cases. In addition, the overall strength of
evidence may be further improved by combining information from chemical profil-
ing studies with information from other investigative approaches (e.g., that provided
by examination of packaging materials, etc.).
26. Several factors may complicate the establishment of specific links between
drug samples. One such factor, independent of source or distribution, is the ageing
of drug samples, i.e., a change in the impurity content of a drug sample due to
decomposition of the main drug and/or accompanying impurities as a result of the
01-83778_1.p65 23/01/2004, 11:11 11
12
conditions to which the sample is subjected, in particular exposure to light, heat and/
or air. Chemical comparison of drug samples related by source, yet exposed to
different environments during the supply chain, could thus suggest that the samples
are not linked. In a similar way, certain aggressive cutting agents (e.g., ascorbic acid)
may alter the composition of a drug sample over time so that the impurity profiles
of samples related by source but seized at different stages of the supply chain may
no longer be the same. The net result is that the chemical comparison of older
samples may not provide any useful information to help link samples together.
C. Establishing drug distribution patterns
27. For natural and semi-synthetic drugs, the prospects of establishing distribution
patterns and networks associated with specific drug manufacturers or trafficking
organizations are limited if they are only based on chemical profiles. This is largely
due to the fact that there is little or no information on what constitutes a batch of
a natural/semi-synthetic drug. Moreover, it is by no means certain that large illicit
consignments of such drugs constitute the product of a single batch (or even of one
drug-producing region). There is also only a limited amount of information on the
extent of variation of manufacturing impurities across batches, countries or geo-
graphic regions with drugs of this type. Consequently, it is extremely difficult to link
together those samples manufactured by the same producer in different batches,
while at the same time discriminating against those samples manufactured by a
different producer in the same region. However, using multiple analytical techniques
with at least one independent method and with support of intelligence information
and physical properties, such a task is not impossible.
28. In addition to difficulties in grouping natural and semi-synthetic drugs based
on the presence of co-extracted and manufacturing impurities, the nature of interna-
tional trafficking in such drugs further complicates attempts to build up major na-
tional or international distribution networks: samples from the same batch (i.e., the
product of a laboratory operation at a given time) are likely to be distributed in
different supply chains (likely to be reflected by the use of different cutting agents
or packaging) to a variety of destinations. Consequently, in building up major na-
tional or international distribution networks, the presence of unusual cutting agents,
and any other relevant information, may therefore be used to group related samples,
in addition to the presence of the manufacturing impurities.
29. Moreover, in attempts to build up major international distribution networks,
the presence of some characteristic cutting agents may also be of further signifi-
cance, because it is believed that some of these substances are added to the illicit
drug material close to the source of drug manufacture. Consequently, those groups
which are made up of samples containing the same characteristic cutting agents may
be associated with specific production or trafficking organizations.
30. For synthetic drugs, provided there is no change in the method or the condi-
tions of drug synthesis, it is possible to build up a network of related samples (i.e.,
a series of samples produced by the same illicit chemist and/or at the same labora-
tory) over a period of time, because inter-batch variations in impurity content of
samples are believed to be relatively small. Similar to the situation with natural and
semi-synthetic drugs, the presence of some characteristic cutting agents in synthetic
drugs may be indicative for specific production or trafficking organizations.
01-83778_1.p65 23/01/2004, 11:11 12
13
D. Identifying the source of drug samples
31. Natural and semi-synthetic drugs on the one hand, and synthetic drugs on the
other, differ in their manufacturing processes as well as in the nature of the starting
materials, i.e., natural raw materials bound to certain geographic regions, or chemi-
cal precursors, respectively. As a consequence, conclusions which can be drawn
from the detailed chemical analysis of either drug type are different: while for
natural and semi-synthetic drugs, at least in theory, an assignment of geographic
origin is possible, this is not the case for synthetic drugs.
32. In general, in characterization studies aimed at identifying the source or geo-
graphic origin of drug samples, it is not necessary to examine the pattern of cutting
agents in the sample as these (in most cases) will bear little or no relation to the
source. Particular efforts have to be directed at concentrating on the examination of
impurity profiles of co-extracted and/or manufacturing impurities in different sam-
ples.
1. Natural and semi-synthetic drugs
33. The chemical characteristics of natural and semi-synthetic drugs are relatively
specific to particular geographic areas of the world because, within any one region,
the factors which influence the natural impurity content of drug samples (e.g., soil,
climatic conditions, etc) may be sufficiently consistent. In addition, clandestine pro-
duction methods in any one region are believed to be closely related. Consequently,
samples of drugs of the same type made by different manufacturers in the same
country or region contain similar proportions of the same core manufacturing impu-
rities and may therefore, in theory, be classified together (the basis of assigning
regions of origin).
34. As a consequence, where a drug sample exhibits the impurity pattern of a
known manufacturing process, and that pattern is characteristic, the origin of the
sample may be attributed to the geographic region or regions where the process is
known to be employed. More specifically, a given sample may be assigned to a
specific region of origin, if its impurity profile has the characteristic impurity pattern
of a sample known to be from that region. A prerequisite to this is the existence of
a well maintained, representative and up-to-date collection of samples of authenti-
cated origin. In the same way, the origin of samples of the raw materials (e.g., coca
leaves, opium) may be identified.
35. However, it is important to recognize that the chemical characteristics of a
given natural or semi-synthetic product could be altered or disguised if, for example,
seedstock was internationally exchanged, or if significant changes to the drug manu-
facturing process were introduced by drug producers. As a result, chemical profiles
would bear little or no relationship to previous samples from the same regional
source or drug producing organization, which would, in turn, severely complicate
the interpretation of chemical profiles and correlation with geographic origin. Obvi-
ously it then becomes difficult if not impossible to classify samples from chemical
profiles alone. The same would be true if the different manufacturing methods were
used freely around the world.
36. In contrast to the identification of the geographic region of origin for natural
and semi-synthetic drugs, it is not possible in practice to relate a series of batches
01-83778_1.p65 23/01/2004, 11:11 13
14
of such drugs to a single source of drug production (i.e., the production site or
specific batch). This is a consequence of the nature of the clandestine production
process of such drugs and the limited knowledge about batch variation with this type
of drugs (see Section 3.B of this Annex). However, as noted above, in cases where
it is known that certain cutting agents are added to natural drug materials close to
the source of drug manufacture, the presence of some characteristic cutting agents
may be of significance and may help to relate samples to specific production organi-
zations.
2. Synthetic drugs
37. For synthetic drugs, practical experience has shown that the impurity profiles
of products from one illicit laboratory are characteristic, at least for some drugs.
Consequently, samples can be classified into groups identified by their chemical
profiles; a given sample or group of samples may be associated with an individual
illicit chemist or laboratory, thus enabling samples from the same source to be linked
together. While such chemical profiling information cannot help to identify the
geographic origin of a synthetic drug sample (i.e., the location of the illicit labora-
tory), it may be used to relate samples from a series of batches to a single chemist
or laboratory, and to identify the source of supply or distribution.
E. Identifying and characterizing the specific starting materials employed in
clandestine drug manufacture
38. In a similar way to the chemical characteristics of finished drug products, the
corresponding starting materials (natural raw products and precursor chemicals) used
in the clandestine production process may also contain certain impurities. The im-
purity content and the type of impurity may vary depending on the nature of the
starting material (e.g., raw opium or a chemical substance), on whether a precursor
chemical was diverted from legitimate sources, or was itself manufactured clandes-
tinely. The identification of characteristic impurities (or patterns of impurities) in
precursors may, therefore, help to relate them to a clandestine (or commercial)
source.
39. In addition, knowledge about the presence of certain impurities in starting
materials may also help to relate finished drug products to the corresponding starting
materials (and ultimately to their source). To this end, an understanding of the
mechanisms leading to the presence of impurities in clandestine drugs is important:
impurities may already be present in the starting materials, and may be carried over
unchanged to the final product; they may arise from reactions of original impurities
present in starting materials; or they may be generated de novo, as by-products
during drug manufacture (they are thus indicative of certain manufacturing routes,
but less useful for the identification of the sources of starting materials). It is this
knowledge which enables the forensic chemist to draw correct conclusions about the
use of certain starting materials, or specific batches of them, in clandestine manu-
facturing processes.
01-83778_1.p65 23/01/2004, 11:11 14

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