The work of the Drugs Intelligence Laboratory, Home Office Forensic Science Service
Author: I. J. HUMPHREYS
Pages: 33 to 46
Creation Date: 1984/01/01
The primary purpose of the Drugs Intelligence Laboratory is to help the police identify sources of supply and manufacture of illicit drugs. This is done by providing scientific support to the Central Drugs and Illegal Immigration Intelligence Unit, a national police unit based at New Scotland Yard, London. The Laboratory provides detailed information on United Kingdom drug seizures and data obtained from a programme of comparison and characterization of seized samples. This intelligence information is then used to supplement that obtained through normal police channels in the search for illicit drug sources, manufacturers or distributors. This paper describes the techniques used for comparing and characterizing various drug preparations and outlines the type of information that can be gained from such studies.
The analysis of illicit drugs, for purposes of determining whether they come under the Misuse of Drugs Act (1971), is carried out in the United Kingdom by the following forensic science laboratories :
Six Home Office laboratories at Chepstow, Aldermaston, Huntingdon, Birmingham, Wetherby and Chorley. These laboratories serve provincial police forces in England and Wales ;
The Metropolitan Police Forensic Science Laboratory (MPFSL) serving the Metropolitan Police force in London ;
Three police laboratories in Glasgow, Edinburgh and Aberdeen serving Scottish police forces ;
A laboratory in Belfast dealing with seizures in Northern Ireland ;
The laboratory of the Government Chemist in London which has responsibility for the analysis of customs seizures.
In addition, the Home Office and police laboratories are supported by the Central Research Establishment whose role includes research and development, evaluations of new techniques and equipment, provision of specialized analytical services and an information service. Within the Drugs and Toxicology Division at the Central Research Establishment is the Drugs Intelligence Laboratory (DIL) whose primary purpose is to help the police identify sources of supply and manufacture of illicit drugs. This Laboratory acts as a scientific support service to the Central Drugs and Illegal Immigration Intelligence Unit which is a national police unit based at New Scotland Yard, London. The terms of reference of the Unit are to collect, collate, analyse and disseminate intelligence about drug offences on a national and international level. The scientific support offered by the DIL may be categorized as follows :
Provision of information on seizures of illicit drugs ;
Comparison and characterization of seized materials ;
Research into and development of new methods of comparison and characterization.
The first of these activities, the information role, is a co-ordinating one. With very few exceptions, all drug seizures in the United Kingdom must be examined in one of the forensic science laboratories referred to above. The DIL, therefore, maintains regular contact with each laboratory in order to monitor seizures and is able to assess trends in drug abuse accurately and Constantly. Data regarding those seizures which are considered to be significant are passed to the Central Drugs and Illegal Immigration Intelligence Unit. The DIL also maintains an international liaison programme with laboratories and law enforcement agencies overseas. Most illicit drugs on the United Kingdom market are imported, hence information and sample exchange with these organizations is an important source of intelligence which has proved valuable in identifying sources of various preparations and their routes of distribution.
Collections of data on seizures are of amphetamine would be of considerable use to an investigating officer if it could be shown that the seizures fell into groups of say 50, 30 and 20 samples from three independent manufacturing sources. The only satisfactory means of establishing this type of relationship is through a detailed physical or chemical comparison of samples. This type of analysis is not routinely undertaken by operational forensic science laboratories whose primary concern is whether or not the materials examined come under the Misuse of Drugs Act (1971). Selected samples are therefore forwarded to the DIL for further examination to establish relationships between exhibits on the basis of common features and to identify specific components which may yield information on the manufacturing processes employed [ l] . This paper outlines the techniques used and the information that can be gained from this programme of comparison and characterization. It will be seen that the actual drug content of the preparations considered plays a minor role in their characterization and that the emphasis is placed on physical characteristics and overall chemical composition including impurities. Many of the techniques used have been developed through the research programme, the third aspect of the Laboratory's work. This is an important part of DIL activities and is under constant review. The techniques used vary according to the form of dosage.
The first type of dosage form to be considered is the tablet. Tablets offer several advantages both to the illicit manufacturer and to the consumer. These include the following :
Drugs such as amphetamine and lysergic acid diethylamide (LSD) require low dosages which cannot easily be dispensed with any accuracy in powder form. The production of tablets enables this difficulty to be overcome;
Tablets may be easily handled and concealed and may be consumed in Circumstances where other forms of consumption, such as injection, would be inconvenient ;
Illicit tablets, like their licit counterparts, allow tentative identification of the active constituents. For example, blue tablets of approximately 8 mm diameter usually contain stimulants such as amphetamine, pemoline or diethylpropion. Small, microdot-size, brightly coloured tablets are characteristic of LSD.
In order to assess the type of information which can be gained from a study of the tablet form, it is first necessary to consider the available methods of production. The most common method of manufacture is that used in the pharmaceutical industry involving the compression of crystals, free-flowing powders or granules between two punches in a die. These punches and dies (see figure I) may be housed in one of two types of tabletting machines, single-punch or multi-punch presses. Single-punch presses are so called because they accommodate one die and one pair of punches producing one tablet at a time. They may be hand-operated or electrically driven. Multipunch presses can accommodate from 16 to over 60 dies and pairs of punches which are carried by a revolving turret. Powder or granules are fed from a hopper into a specially designed frame which distributes the material into the dies for compression into tablets. Whichever type of machine is used, the heat-toughened Surfaces of the punches are susceptible to physical damage through mishandling or incorrect alignment. The damage marks or "punch marks" will then be transferred to every tablet which the punches produce. This provides a means whereby the forensic scientist can relate tablets seized to their manufacturing source [ 2] . The shadows cast by the depressions or ridges present on the tablet surface are highlighted using a low-power microscope and oblique lighting. This is a method akin to that used for examining bullet and tool marks.
Punch and dies from single-punch (left) and multi-punch (right) presses
The parts of a tablet surface which most frequently bear such marks are the areas of depression such as bevelled edges or score-lines. This is because, on the punch used for production, these features are "proud" to the surface and hence more prone to damage by dropping, wear etc.
The presence of an identical mark on every tablet indicates the use of a single-punch machine. If, however, several different punch marks recur amongst a batch of tablets, then production on a multi-punch machine is inferred. This indication of the type of equipment used also establishes the potential output of the manufacturing source.
When no obvious punch mark is present, greater emphasis must be placed on the next stage of the physical examination of tablets. This involves the accurate measurement of dimensions some of which require the use of a system developed for the purpose in the DIL [ 3] . The apparatus employed uses the "shadowgraph" technique to project an accurately magnified silhouette of the tablet on to the graduated screen of a projection microscope. This enables the accurate measurement of fine details such as the width, depth and angle of any score-line or bevelled edge present. Any unusual feature of these measurements may be used to characterize the preparation, thus providing a means of linking different seizures to the same source. Measurement of the radius of curvature of biconvex tablets using a projection microscope has also proved useful in this respect. Several biconvex LSD tablets of different colours were assigned to the same manufacturer on the basis that the opposite faces of the tablets had markedly different radii of Curvature. This was probably attributable to the use of reground or home-made punches.
There is an alternative method of tablet manufacture which does not require the use of the type of machinery described above. The principle of this other process is to make up a paste with the drug, a diluent, a dye and water (or other liquid) and to spread this on to a mould consisting of, for example, a perforated metal sheet. The paste is then dried and the tablets are pushed or allowed to fall out. Tablets produced in this manner may be fairly readily recognized. In general, unlike their compressed Counterparts, the surfaces tend to be rough and the tablets are irregular due to the distortion which occurs in drying. It is, therefore, possible to indicate whether, for a given trend in tablet distribution, there is any need to look for a tablet machine or whether to expect the laboratory or factory responsible to contain merely a number of sheets of drilled hard board, plastic, metal or other material.
Tablets moulded in this way will not of course bear any punch marks and the distortion which occurs in the drying process means that they do not lend themselves very well to comparison by projection microscope. Any direct comparison between batches seized therefore requires a chemical examination. This indeed may be carried out on all tablet forms.
As mentioned earlier, one of the principal reasons for tablet manufacture, both licit and illicit, is to provide a medium for the handling and distribution of small doses of drug designed for oral ingestion. Many tablets found on the illicit market contain only a small percentage of drug. The remainder of the material present in the preparation can be used for purposes of comparison and Correlation of samples some of which may have previously been considered as unrelated on the basis of the physical evidence alone (different size, shape etc.).
The first material of interest is that used to give the tablet its bulk. This bulking agent, or major excipient, is an inert substance representing around 90 per cent of the tablet's weight. The choice of material is somewhat limited as the bulking agent must not affect the action of the drug in any way, should be fit for consumption and, in the case of machine-made tablets, must be compressible. Commonly used excipients include lactose, dried milk and Calcium phosphate. The high concentration of the bulking agent in tablets means that it can often be identified by subjecting a tablet scraping to infrared spectroscopy with no prior extraction of the sample. The quantities of other components present, including the drug, are generally not sufficient to interfere with the spectrum [ 4] . Figure II shows the similarity between the infrared spectrum of a microdot LSD tablet and that of a control sample of calcium lactate. This unusual bulking agent was found in a number of different LSD tablets and provided good evidence of a link between seizures.
Comparison of the infrared spectra of an LSD microdot tablet and a control sample of calcium lactate
Mixtures of bulking agents provide even better evidence of seizure links. Binary mixtures may be resolved and identified using a wedge-disc Compensating technique [ 4] or by employing a spectrophotometer with a dedicated computer facility.
The second tablet component of interest is the colouring agent. Tablets are generally coloured to add to their aesthetic appeal and colour may be used to identify a particular batch or type. For example, illicit amphetamine tablets are often pale blue, largely because of attempts to copy a particular brand of licit amphetamine tablet which was subject to heavy abuse in the 1960s. Pharmaceutical manufacturers are very much restricted by law in the colouring dyes that they may use. The illicit manufacturer is not, however, subject to this legal restraint and may use anything from a food-colouring dye, readily obtainable at a supermarket, to a tin of fabric dye. Whichever type of dye is used, it does provide another factor in the comparison of samples [ 5] .
A three-step analysis for the identification of soluble food dyes has been developed in the DIL [ 6] . The procedure involves thin-layer chromatography, visible spectrophotometry and reversed-phase ion-pair high performance liquid Chromatography (HPLC). Soluble food dyes are a very common form of colouring agent found in illicit tablets and the HPLC method has also been found to be of value in distinguishing the differences which occur in the number and nature of impurities present in these dyes from different manufacturers or batches [ 7] . Further confirmation of similarities between samples may therefore be provided.
In recent years, increasing use has been made by clandestine manufacturers of the insoluble "lake dyes" which are used in the pharmaceutical industry to prepare tablets with an even colour distribution and a low tendency to mottling. The comparative efficiency of several reagents for the liberation of dyes from their insoluble extenders has been studied [ 8] and HPLC may now be used on the resulting extracts from such dyes in illicit preparations.
Possibly the next most obvious choice of colouring agent for the illicit manufacturer is the range of readily available fabric dyes, although the author is not aware that these dyes have actually been used in illicit preparations to date. It has been shown that it is possible to use HPLC in the separation of the many coloured components which make up typical fabric dyes such as the range of Dylon multipurpose dyes [ 9] . All the products in the Dylon multipurpose dye range which were examined exhibited different analytical characteristics. Hence, if one of these products did occur in an illicit preparation, it could be readily identified. The presence of the same Dylon product in separate illicit drug seizures would provide good evidence of a link between them.
Other materials which are essential in the production of machine compressed tablets include small quantities of binders and lubricants. One would therefore expect to encounter such substances as starch, gelatin and stearates in tablets of this nature. Any particularly unusual feature of these materials, or indeed of the other components of the tablet formulation, increases the evidential value of comparisons and may even provide a lead as to where they originated.
Finally, a typical illustration of how the techniques described have been used to link different seizures to the same source is given in figure 111. The tablets shown are all pale blue, amphetamine tablets which were prominent on the illicit market in 1974 and 1975. They differ from each other in size and shape but analysis showed that, as well as amphetamine, the following ingredients were present in each type : amylobarbitone, corn starch, calcium carbonate, calcium lactate, stearic acid, palmitic acid and indigo carmine dye. With such a unique combination of chemicals it was reasonable to assume that all three physically different preparations were made by the same manufacturer. This was later proved to be correct.
Three physically dissimilar amphetamine tablets with the same chemical composition
Another dosage form encountered from time to time is the capsule. As with tablets, capsules can bear characteristic markings, but these arise in a quite different manner. Capsules have a locking mechanism, in the form of indentations or ridges moulded into the gelatin shells, so that the cap and body are held firmly together. In general, this mechanism is in two parts. The first part is the so-called pre-lock for sending the capsule to where it is to be filled. The cap and body are loosely held together so that they can be easily parted for filling. When filled, the cap is pushed past the pre-lock position to the full lock. The limited number of manufacturers of capsule shells in the United Kingdom each use a different version of this locking system which allows their own product to be readily identified. Therefore, in any instance where capsule shells have been purchased and filled for illicit sale, an approach can be made to the original manufacturer, with details of the colour combination of cap and body, so that the customers who purchased them may be identified. Unusual colour combinations may lead directly to the source of illicit drug supply.
Illicit drugs may also occur as powders. In these instances, the chemical characteristics are examined. The production of drugs inevitably leads to the co-production of many other materials which, unless sustained attempts are made to remove them by purification, will remain in the sample as impurities. The presence of these impurities provides a means of:
Establishing the synthetic route employed. This is useful in linking an illicit laboratory to seized material and also in providing information on the starting chemicals and expertise required for production ;
Providing evidence of a link between seized Samples or between material found at a laboratory and that circulating on the drug scene.
Taking these points in turn, the most convenient way of establishing the method by which a drug has been produced is to detect the presence of a side product of manufacture which is specific to a particular synthetic route. This can be achieved by identifying the impurities in illicit samples with the aid of gas chromatography/mass spectrometry and postulating their mode of production. An alternative approach, which has been employed in the DIL, is to synthesize the drug by various routes and to identify the materials produced in Side reactions. With this approach, the significance of the presence of various impurities is easier to interpret since the route of synthesis is known. An example of the procedure is seen in the Leuckart route of amphetamine manufacture shown in figure IV. In this reaction the action of formamide on benzyl methyl ketone (1) in the presence of formic acid produces N-formylamphetamine (2) which is readily hydrolysed with sulphuric acid to amphetamine (3). One side reaction which appears to occur, however, is a condensation reaction between the intermediate N-formylamphetamine and benzyl methyl ketone to produce isomers of the compound N-formyldi(l-isopropylphenyl)amine [ 10] , [ 11] . These isomers give rise to a pair of very characteristic peaks in gas chromatographic impurity-pattern traces obtained from "home-made", Leuckart-produced amphetamine. They were found to persist in all samples prepared, despite attempts at purification. Their formation could not easily be explained by the use of any other route of amphetamine production. The isomers were therefore considered to be excellent "markers" for the Leuckart route and the subsequent analysis of a large number of illicit samples has supported this belief.
The Leuckart route of amphetamine manufacture
The second way of establishing a link between seized Samples also relies on a study of the impurities present. The method involves extracting a salt of the drug with an organic solvent from a neutral aqueous solution which leaves the bulk of the drug in the aqueous layer. The concentrated organic layer, which contains trace impurities, is then subjected to gas chromatography with temperature programming and the impurity patterns produced are compared visually [ 12] , [ 13] . A Series of chromatograms which match in all respects could indicate either that the samples from which they were obtained were taken from the same batch or that the same production method had been used with similar reaction conditions. A further study of the Leuckart reaction has shown that variations in reaction conditions have a marked effect on the production of known intermediates or side products [ 14] . In addition, attempts to reproduce the same impurity patterns by repeated syntheses, under experimental conditions within very strict limits, were unsuccessful. We therefore conclude that when a gas chromatographic impurity pattern is obtained from one sample which matches that from another in all respects, the two samples have been taken from the same batch.
Both methods of the analysis of powdered Samples described here have been based on and illustrated by the drug amphetamine, but the methods are equally applicable to any illicitly produced powdered drug.
In an analogous manner to that employed for powdered drugs, it is possible to obtain "fingerprint" patterns showing the large number of cannabinoid constituents in a sample of cannabis or cannabis resin [ 15] . However, to obtain this information by chromatographic means and then to attempt to correlate the patterns obtained from the countless seizures of cannabis and cannabis resin would be a mammoth task. Fortunately, in many instances cannabis resin or its associated packaging bears some form of identification mark which is thought to be added to the resin by the organization responsible for its production or by a trading establishment in its country of origin (figure V). This provides a means of linking seizures by visual inspection without resorting to chemical analysis. It is accepted that blocks of resin bearing the same "brand" mark can have completely different cannabinoid contents. Nevertheless, the markings suggest the same source for the resin at an early stage after production. With this in mind, the marks may be used as a basis for providing information to the police on the extent of distribution and possible area of origin of connected seizures.
An example of a "brand" mark on the cloth-bag wrapping of a block of cannabis resin
Another solid dosage form is paper or card which has been spotted or impregnated with LSD. This is an increasingly popular means of dispensing LSD and the number of seizures of this dosage form in the United Kingdom is now much greater than the number of seizures in tablet form. In many instances, as with the cannabis resin discussed above, the paper or card doses bear an identification mark in the form of various types of design, either on individual doses or covering a sheet of up to 500 doses. This allows material from the same source to be readily recognized. Not all paper doses, however, are so marked. It may also be a fact that one manufacturer is responsible for producing LSD papers bearing many different designs. In order to establish links in these cases, it is necessary to rely on chemical analysis. Once again, the purity of the LSD drug depends very much on the synthetic method used and the technical competence of the manufacturer. If little or no attempt has been made during manufacture to separate the LSD from the side products
High-performance liquid chromatography with fluorescence detection of an LSD card dose extracted with methanol
of the synthesis and the residual amounts of unreacted Starting material, the number and relative amounts of these compounds in a preparation may be used to characterize it. LSD and related materials can be readily separated using HPLC and, because many of the compounds are fluorescent, they may be detected with a spectrofluorimeter. Figure VI shows the results obtained from the analysis of one LSD card dose. Peaks 1 and 2 are as yet unidentified Components, peak 3 appears to he a trace of ergotamine (starting material), 4 is LSD and 5 is the chemical iso-LSD which often occurs in illicitly produced LSD but rarely in such a high proportion. Several card doses of different colours and bearing various designs produced an HPLC trace matching that shown here, which leaves little doubt that, despite their physical differences, the preparations originated from the same manufacturer.
In Conclusion, illicit drugs take many different dosage forms. The primary interest of United Kingdom police officers who have seized Substances, suspecting that they may be drugs, is whether or not the materials contravene the Misuse of Drugs Act (1971), and it is the task of the forensic scientist to establish this. In many cases, as described above, there is also a wealth of information to be gained from a study of the features characteristic of the various drug forms which can be used to assist the police in identifying manufacturing methods, relating different seizures to the same source and establishing their origin. The provision of that information is the contribution made by the Drugs Intelligence Laboratory of the Home Office Forensic Science Service.
D. G. Sanger, I. J. Humphreys and J. R. Joyce, "A review of analytical techniques for the comparison and characterization of illicit drugs", Journal of the Forensic Science Society, vol. 19, 1979, pp. 65 - 71.02
P. J. Gomm, I. J. Humphreys and N. A. Armstrong, "Physical methods for the comparison of illicitly produced tablets", Journal of the Forensic Science Society, vol. 16, 1976, pp. 283 - 293.03
P.J. Gomm, "A technique for the physical examination of illicitly made tablets", Journal of the Forensic Science Society, vol. 15, 1975, pp. 219 - 226.04
P.J. Gomm and I. J. Humphreys, "Identification of the major excipients in illicit tablets using infrared spectroscopy", Journal of the Forensic Society, vol. 15, 1975, pp. 293 - 299.05
J. R. Joyce, "The identification of dyes in illicit tablets", Journal of the Forensic Science Society, vol. 20, 1980, pp. 247 - 252.06
J. R. Joyce and D. G. Sanger, "A procedure for the identification of soluble food dyes in illicit drug preparations", Journal of the Forensic Science Society, vol. 19, 1979, pp. 203 - 209.07
J. R. Joyce and I. J. Humphreys, "The detection of trace impurities in soluble food dyes", Journal of the Forensic Science Society, vol. 22, 1982, pp. 253 - 256.08
J. R. Joyce and D. G. Sanger, "Comparison of extraction procedures for insoluble food dyes in illicit drug preparations", Journal of the Forensic Science Society, vol. 20, 1980, pp. 177 - 181.09
J. R. Joyce, D. G. Sanger and I. J. Humphreys, "The use of HPLC for the discrimination of a range of dylon home-dyeing products and its potential use in the comparison of illicit tablets", Journal of the Forensic Science Society, vol. 22, 1982, pp. 337 - 341.10
I. J. Humphreys, D. G. Sanger and R. E. Ardrey. Unpublished results.11
T. C. Kram, "Re-identification of a major impurity in illicit amphetamine", Journal of Forensic Sciences, vol. 24, 1979, pp. 596 - 599.12
D. G. Sanger, I. J. Humphreys and R. E. Ardrey. Unpublished results.13
L. Stromberg, "Comparative gas chromatographic analysis of narcotics II. Amphetamine sulphate", Journal of Chromatography, vol. 106, 1975, pp. 335 - 342.14
D. G. Sanger and I. J. Humphreys. Unpublished results.15
B. B. Wheals and R. N. Smith, "Comparative cannabis analysis. A comparison of high-pressure liquid chromatography with other chromatographic techniques", Journat of Chromatography, vol. 105, 1975, pp. 396 -400.