A review of recent advances in impurity profiling of illicit MDMA samples

Profiling illicit ecstasy tablets has the potential to become an invaluable tool in the crackdown on drug trafficking, but that potential has yet to be fully realized. The impurity profile of an ecstasy tablet can be used to determine the method employed to synthesize the actual controlled substance, which in most cases, is 3,4-methylenedioxymethamphetamine (MDMA). Tablets can then be linked to a common synthetic route, potentially to a common manufacturer, and possibly even to a common manufacturing batch, based on the impurities present. Current methods for profiling MDMA tablets typically involve extracting the organic impurities for analysis by gas chromatography-mass spectrometry. The potential of profiling the trace metals present in tablets has begun to be investigated while more robust statistical and chemometric procedures are being applied to compare and link tablets. This article reviews the recent advances in MDMA impurity profiling from 2002 up to the end of 2006.     

Surface granularity as a discriminating feature of illicit tablets

In this paper we propose an innovative methodology for automated profiling of illicit tablets by their surface granularity; a feature previously unexamined for this purpose. We make use of the tiny inconsistencies at the tablet surface, referred to as speckles, to generate a quantitative granularity profile of tablets. Euclidian distance is used as a measurement of (dis)similarity between granularity profiles. The frequency of observed distances is then modelled by kernel density estimation in order to generalize the observations and to calculate likelihood ratios (LRs). The resulting LRs are used to evaluate the potential of granularity profiles to differentiate between same-batch and different-batches tablets. Furthermore, we use the LRs as a similarity metric to refine database queries. We are able to derive reliable LRs within a scope that represent the true evidential value of the granularity feature. These metrics are used to refine candidate hit-lists form a database containing physical features of illicit tablets. We observe improved or identical ranking of candidate tablets in 87.5% of cases when granularity is considered.     

A rapid and sensitive method for the identification of delta-9-tetrahydrocannabinol in oral fluid by liquid chromatography-tandem mass spectrometry

This paper proposes a new approach for automatic classification of counterfeit Viagra(?) and Cialis(?) tablets using image processing and statistical analysis. A high resolution VSC 5000 is used for image acquisition in a controlled environment, and the combination of a thresholding technique with morphological operators is used to segment the tablet from the background. A statistical model based on the RGB color components of original samples is built, and the detection of counterfeit tablets was performed by checking the adherence of a test sample to the obtained distribution using the Bhattacharyya distance. Our experimental results indicated that counterfeit tablets can be effective detected using the proposed approach.     

Synthesis of 4-methyl-5-arylpyrimidines and 4-arylpyrimidines: route specific markers for the Leuckardt preparation of amphetamine, 4-methoxyamphetamine, and 4-methylthioamphetamine

General synthetic routes to 4-methyl-5-arylpyrimidines and 5-arylpyrimidines are described. 4-Benzylpyrimidine, 4-methyl-5-phenylpyrimidine, 4-(4-methoxybenzyl)pyrimidine, and 4-methyl-5-(4-methoxyphenyl)pyrimidine have been positively identified as route-specific by-products in the Leuckardt preparations of amphetamine and 4-methoxyamphetamine.Using headspace solid phase microextraction (SPME) 4-(4-methoxybenzyl)pyrimidine and 4-methyl-5-(4-methoxyphenyl)pyrimidine have been identified in illicit tablets containing 4-methoxyamphetamine. This is an indication that illicit laboratories use the Leuckardt method for the preparation of 4-methoxyamphetamine.Flatliner tablets containing 4-methylthioamphetamine have been screened for the presence of 4-(4-methylthiobenzyl)pyrimidine and 4-methyl-5-(4-methylthiophenyl)pyrimidine using both headspace and aqueous phase SPME. As these pyrimidines were not detected it would appear likely that illicit laboratories are not using the Leuckardt method for the preparation of 4-methylthioamphetamine.     

Irrational Addicts and Responsible Pleasure Seekers: Constructions of the Drug User

Historically, drug use has been understood as a problem of epidemiology, psychiatry, physiology, and criminality requiring legal and medical governance. Consequently drug research tends to be underpinned by an imperative to better govern, and typically proposes policy interventions to prevent or solve drug problems. We argue that categories of ‘addictive’ and ‘recreational’ drug use are discursive forms of governance that are historically, politically and socially contingent. These constructions of the drug problem shape what drug users believe about themselves and how they enact these beliefs in their drug use practices. Based on qualitative interviews with young illicit drug users in Brisbane, Australia, this paper uses Michel Foucault’s concept of governmentality to provide insights into how the governance of illicit drugs intersects with self-governance to create a drug user self. We propose a reconceptualisation of illicit drug use that takes into account the contingencies and subjective factors that shape the drug experience. This allows for an understanding of the relationships between discourses, policies, and practices in constructions of illicit drug users.     

DNA on drugs

The use of illicit drugs is a continuing blight on society. Detecting DNA from individuals involved in the manufacturing and distribution of drugs can provide valuable investigative information or strategic intelligence which, in turn, can be used to disrupt the supply and distribution of illicit drugs. Our study details the transfer, persistence, prevalence, and recovery of human DNA on the exterior of tablets and capsules, as well as within drug powders. Various experiments were conducted to mimic stages in the creation and packaging of tablets and capsules. We showed that the act of brief contact (1–3 s) is sufficient to generate informative DNA profiles that can be uploaded and compared to databases internationally. This work complements chemical drug profiling data by linking seizures to each other and individuals via DNA profiles, providing information to prosecution or intelligence agencies. The generation of DNA information from illicit drug preparations is another tool that can be used in the fight against illicit drug manufacture and distribution.     

Elemental analysis of 3,4-methylenedioxymethamphetamine (MDMA): A tool to determine the synthesis method and trace links

The elemental composition of 3,4-methylenedioxymethamphetamine (MDMA) powders and tablets was determined. The objective was the identification of the synthesis method and application of the elemental profile in comparative analysis. The developed analytical method comprised the digestion of a sample followed by quantitative analysis with inductive coupled plasma mass spectrometry (ICP-MS) and inductive coupled plasma atomic emission spectroscopy (ICP-AES). The sample collection consisted of a unique set of MDMA powders (57) from illicit production sites and MDMA tablets (97) taken from large seizures (over 500 tablets) in the Netherlands. The production method of MDMA could be determined for 89 of the 97 tablets. In 84 cases reductive amination using Pt as the catalyst was used, in four cases reductive amination using NaBH(4) or a similar reducing agent was employed and one mixed sample (Pt and B) was found. None of the MDMA tablets were assigned to the aluminium amalgam method. Using the elemental profile, 13 links were identified within the 97 MDMA tablets using cluster analysis based on Pearson correlations. Of these links 10 were corroborated by additional analyses.     

Sample Size Determination for Categorical Responses

Abstract:  Procedures are reviewed and recommendations made for the choice of the size of a sample to estimate the characteristics (sometimes known as parameters) of a population consisting of discrete items which may belong to one and only one of a number of categories with examples drawn from forensic science. Four sampling procedures are described for binary responses, where the number of possible categories is only two, e.g., licit or illicit pills. One is based on priors informed from historical data. The other three are sequential. The first of these is a sequential probability ratio test with a stopping rule derived by controlling the probabilities of type 1 and type 2 errors. The second is a sequential variation of a procedure based on the predictive distribution of the data yet to be inspected and the distribution of the data that have been inspected, with a stopping rule determined by a prespecified threshold on the probability of a wrong decision. The third is a two-sided sequential criterion which stops sampling when one of two competitive hypotheses has a probability of being accepted which is larger than another prespecified threshold. The fifth procedure extends the ideas developed for binary responses to multinomial responses where the number of possible categories (e.g., types of drug or types of glass) may be more than two. The procedure is sequential and recommends stopping when the joint probability interval or ellipsoid for the estimates of the proportions is less than a given threshold in size. For trinomial data this last procedure is illustrated with a ternary diagram with an ellipse formed around the sample proportions. There is a straightforward generalization of this approach to multinomial populations with more than three categories. A conclusion provides recommendations for sampling procedures in various contexts.     

The Variability of Ecstasy Tablets Composition in Brazil

The content of ecstasy tablets has been changing over the years, and nowadays 3,4‐methylenedioxymethamphetamine (MDMA) is not always present in the tablets. The aim of this study was to investigate the chemical composition in the seized tablets labeled as ecstasy. We analyzed samples from 150 different seizures made by Sao Paulo's State Police by gas chromatography–mass spectrometry. MDMA was present in 44.7% of the analyzed samples, and another twenty different active substances were identified in these tablets, such as caffeine, 2C‐B, piperazines, amphetamines, phencyclidine, and others. Methamphetamine was present in 22% of these samples. The results demonstrate a huge shift in the pattern of trafficking of synthetic drugs, where MDMA has been replaced in tablets mostly by illicit psychoactive substances, in a clear attempt to bypass the law. The great variability in the tablets composition may lead to an increased risk of drug poisoning.     

Solid-phase extraction for profiling of ecstasy tablets

A solid-phase extraction (SPE) procedure has been developed for impurity profiling of illicit tablets containing 3,4-methylenedioxy-N-methyl-amphetamine (MDMA, ecstasy). Following initial comparison of liquid-liquid extraction and solid-phase extraction, SPE was found to be preferable because it afforded higher extraction efficiencies and shorter extraction times. Procedure blank samples were also analyzed to identify constituents of the extracts which did not originate in the ecstasy tablets. The developed procedure was subsequently applied to 12 samples of seized ecstasy tablets and a comparison was made of these samples to determine similarities and obtain inferences with respect to commonality of origin.     

Organic impurity profiling of 3,4-methylenedioxymethamphetamine (MDMA) tablets seized in The Netherlands.

In this study, a new method was developed for the impurity profiling of illicit MDMA tablets. The extraction efficiency, linearity, repeatability and reproducibility of the method were evaluated. Eighty two MDMA tablets coming from presumed unrelated large seizures in 2004 (n >500 tablets) were analyzed by gas chromatography mass spectrometry (GC-MS) in order to assess the discrimination power of the method. The latter was found to be practical, robust, relatively easy to perform, highly discriminative and yielding good chromatography. In addition, some new impurities were detected and identified. Their chemical structures and mass spectra are reported.     

The analysis of illicit methaqualone containing preparations by gas chromatography-mass spectrometry for forensic purposes

A validated gas chromatographic-mass spectrometric method for quantitative analysis of methaqualone (MTQ) in illicit preparations is reported. The method proved to have a coefficient of variation of below 5%. Four batches of seized tablets, two pairs with similar imprints, were analyzed. It was found that the average MTQ concentration in all four batches of tablets differed significantly (p = 0.01) rendering it impossible to conclude that, on the basis of MTQ concentration alone, the batches with a similar logo originated from the same manufacturer or manufacturing batch. Conversely, it can be said that in this case, the four batches originated from either different clandestine laboratories or manufacturing batches.     

NIR analysis of cellulose and lactose--application to ecstasy tablet analysis

Cellulose and lactose are the most frequently used excipients in illicit ecstasy production. The aim of this project was to use near infrared reflectance spectroscopy (NIRS) for the determination of the different chemical forms of these two substances, as well as for the differentiation of their origin (producer). It was possible to distinguish between the different chemical forms of both compounds, as well as between their origins (producers), although within limits. Furthermore, the possibilities to apply NIR for the analysis of substances such as found in illicit tablets were studied. First, a few cellulose and lactose samples were chosen to make mixtures with amphetamine at three degrees of purity (5, 10 and 15%), in order to study the resulting changes in the spectra as well as to simultaneously quantify amphetamine and identify the excipient. A PLS2 model could be build to predict concentrations and excipient. Secondarily, the technique was to be applied to real ecstasy tablets. About 40 ecstasy seizures were analysed with the aim to determine the excipient and to check them against each other. Identification of the excipients was not always obvious, especially when more than one excipient were present. However, a comparison between tablets appeared to give groups of similar samples. NIR analysis results in spectra representing the tablet blend as a whole taking into account all absorbing compounds. Although NIRS seems to be an appropriate method for ecstasy profiling, little is known about intra- and intervariability of compression batches.     

Using Cluster Analysis and ICP‐MS to Identify Groups of Ecstasy Tablets in Sao Paulo State,Brazil

The variations found in the elemental composition in ecstasy samples result in spectral profiles with useful information for data analysis, and cluster analysis of these profiles can help uncover different categories of the drug. We provide a cluster analysis of ecstasy tablets based on their elemental composition. Twenty‐five elements were determined by ICP‐MS in tablets apprehended by Sao Paulo's State Police, Brazil. We employ the K‐means clustering algorithm along with C4.5 decision tree to help us interpret the clustering results. We found a better number of two clusters within the data, which can refer to the approximated number of sources of the drug which supply the cities of seizures. The C4.5 model was capable of differentiating the ecstasy samples from the two clusters with high prediction accuracy using the leave‐one‐out cross‐validation. The model used only Nd, Ni, and Pb concentration values in the classification of the samples.     

Bruised Inside Out: The Adverse and Abusive Life Histories of Incarcerated Women as Pathways to PTSD and Illicit Drug Use

The majority of incarcerated women who suffer from diverse traumatic life histories including abusive home lives and intimate partner violence (IPV), develop post-traumatic stress disorder (PTSD) and struggle with heavy illicit drug use. While many have offered examinations of these relationships, the current study is among the first to utilize an integrated feminist pathways and general strain theory (GST) approach to explain them. Using data from a stratified random sample of all incarcerated women in Oklahoma (N = 334), we explore the links between, adverse childhood experiences, including physical, sexual, emotional, and childhood neglect, IPV, PTSD, and heavy illicit drug use. Our findings indicate that the effects of IPV on heavy illicit drug use are mediated by PTSD symptoms suggesting that PTSD plays a significant role in the pathway to illicit drug use among Oklahoma women prisoners. Implications for the importance of utilizing an integrated feminist pathways and GST approach in future research are offered.     

A rapid gas chromatographic method for the fingerprinting of illicit cocaine samples.

A gas chromatographic (GC) fingerprint method, based on the presence or absence of six congeners, was developed for illicit cocaine samples. The fingerprint utilizes the relative abundances of these congeners towards each other, disregarding cocaine as the main constituent, and can be expressed numerically or graphically in the form of pictograms for rapid visual comparison. The method can be applied directly to a solution of the sample in chloroform, without previous workup procedures. More than 70 unrelated samples were analyzed and a great variation was observed in the parameter composition. On the other hand, a remarkable similarity could be seen between related samples. The GC fingerprint method may be considered an important contribution for sample comparison, as is exemplified by a subdivision of the analyzed samples in different categories, based on the number and types of congeners found.     

The identification of 2-chloro-4,5-methylenedioxymethylamphetamine in an illicit drug seizure

This work outlines the unequivocal identification of the "ecstasy" analog, 2-chloro-4,5-methylenedioxymethylamphetamine, using combined gas chromatography/mass spectroscopy (GC/MS) and proton magnetic resonance spectroscopy (1H-NMR). This compound was identified along with 3,4-methylenedioxymethylamphetamine (MDMA) in an illicit tablet seizure, which included 26 off-white tablets.     

Determination of Inorganic Ion Profiles of Illicit Drugs by Capillary Electrophoresis

A portable capillary electrophoresis instrument with dual capacitively coupled contactless conductivity detection (C⁴D) was used to determine the inorganic ionic profiles of three pharmaceutical samples and precursors of two illicit drugs (contemporary samples of methylone and para‐methoxymethamphetamine). The LODs ranged from 0.10 μmol/L to 1.25 μmol/L for the 10 selected cations, and from 0.13 μmol/L to 1.03 μmol/L for the eight selected anions. All separations were performed in less than 6 min with migration times and peak area RSD values ranging from 2 to 7%. The results demonstrate the potential of the analysis of inorganic ionic species to aid in the identification and/or differentiation of unknown tablets, and real samples found in illicit drug manufacture scenarios. From the resulting ionic fingerprint, the unknown tablets and samples can be further classified.     

Broken Hearts and Battered Lives: Adverse and Abusive Life Histories and Externalized Responses to Anger as Pathways to Illicit Drug Use Among Incarcerated Women

Most incarcerated women suffer from adverse and abusive life histories, including adverse childhood experiences (ACEs), such as sexual, physical, emotional abuse, and neglect, and intimate partner violence (IPV). In addition, many have difficulties regulating their anger expression and most participate in illicit drug use. Although many have offered explanations for these relationships, the current study is among the first to utilize an integrated feminist pathways and general strain theory (GST) approach to explain them. Using data from a stratified random sample of all incarcerated women in Oklahoma (N?=?441), we explore the linkages between ACEs, IPV, the externalized expression of anger, and heavy illicit drug use. Our findings indicate that childhood physical and sexual abuse are significantly associated with externalized responses to anger. However, the effects of childhood adversities, particularly sexual abuse, on heavy illicit drug use are mediated by externalized responses to anger suggesting that anger plays a significant role in women’s pathways to illicit drug use. In contrast, and somewhat surprisingly, being a victim of IPV was negatively related to externalized responses to anger and not significantly related to illicit drug use. Implications for the importance of utilizing an integrated feminist pathways and GST approach in future research are offered.