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.     

A Simple and Effective Physical Characteristic Profiling Method for Methamphetamine Tablet Seized in China

Methamphetamine (MA) tablet production confers chemical and physical properties. This study developed a simple and effective physical characteristic profiling method for MA tablets with capital letter “WY” logos, which realized the discrimination between linked and unlinked seizures. Seventeen signature distances extracted from the “WY” logo were explored as factors for multivariate analysis and demonstrated to be effective to represent the features of tablets in the drug intelligence perspective. Receiver operating characteristic (ROC) curve was used to evaluate efficiency of different pretreatments and distance/correlation metrics, while “Standardization + Euclidean” and “Logarithm + Euclidean” algorithms outperformed the rest. Finally, hierarchical cluster analysis (HCA) was applied to the data set of 200 MA tablet seizures randomly selected from cases all around China in 2015, and 76% of them were classified into a group named after “WY‐001.” Moreover, the “WY‐001” tablets occupied 51–80% tablet seizures from 2011 to 2015 in China, indicating the existence of a huge clandestine factory incessantly manufacturing MA tablets.     

Characteristics and trends of 3,4-methylenedioxymethamphetamine (MDMA) tablets found in Taiwan from 2002 to February 2005

One hundred and eighty-one 3,4-methylenedioxymethamphetamine (MDMA) containing tablets were sampled from confiscated drugs received by the Taiwan National Bureau of Controlled Drugs for testing from 2002 to February 2005. Sample tablets demonstrated various colors and logos. The appearances, contents of MDMA and other components in these tablets were analyzed in order to understand the characteristics and trends of MDMA use. Samples were analyzed using GC-MS methodology. Deuterated internal standards were used for drug quantification. The MDMA contents varied from 16 to 193 mg/tablet. 66-71% of the tablets seized each year contained only MDMA, and the content of MDMA in MDMA only tablets varied from 89 to 133 mg/tablet. There was a decreasing trend in MDMA content in these tablets over time. Other components commonly found besides MDMA included caffeine (18%), methamphetamine (7%), 3,4-methylenedioxyethylamphetamine (MDEA) (7%) and amphetamine (4%). 3,4-Methylenedioxyamphetamine (MDA), ketamine, ephedrine, diazepam, chlorzoxazone and nicotinamide were also detected. During the study period, the number of other drugs found as well as the combinations of different drugs detected in these tablets increased.     

"Life expectancy" of "ecstasy" tablets in Israel in the years 2001-2003

3,4-Methylenedioxymethamphetamine (MDMA) tablets known as "ecstasy" became a very popular drug amongst Israeli youth in the last decade. The ecstasy tablets have a simple design impressed on them (logos) making it relatively easy to distinguish between various logos. The life expectancy of ecstasy tablet logos, defined as the period between the first seizure by the police of a certain logo until the last seizure of the same logo, was monitored during the years 2001-2003. During this time interval, 58 different tablet logos were seized. A total of 26 logos, defined as common logos with at least 10 independent seizures, were observed. At any given time interval during this period, 8-10 common logos were found with an average life expectancy of approximately 9 months. Five of the observed 26 common logos were defined as the most common logos that appeared in at least 200 independent seizures each. Plots of the number of seizures and number of tablets seized as a function of time are presented and discussed as well as explanations for the high turnover rate of any given logo.     

Analysis of Ecstasy Tablets Using Capillary Electrophoresis with Capacitively Coupled Contactless Conductivity Detection

A method for the identification of 3,4‐methylenedioxymethamphetamine (MDMA) and meta‐chlorophenylpiperazine (mCPP) was developed employing capillary electrophoresis (CE) with capacitively coupled contactless conductivity detection (C⁴D). Sample extraction, separation, and detection of “Ecstasy” tablets were performed in <10 min without sample derivatization. The separation electrolyte was 20 mm TAPS/Lithium, pH 8.7. Average minimal detectable amounts for MDMA and mCPP were 0.04 mg/tablet, several orders of magnitude lower than the minimum amount encountered in a tablet. Seven different Ecstasy tablets seized in Rio de Janeiro, Brazil, were analyzed by CE‐C⁴D and compared against routine gas chromatography‐mass spectrometry (GC‐MS). The CE method demonstrated sufficient selectivity to discriminate the two target drugs, MDMA and mCPP, from the other drugs present in seizures, namely amphepramone, fenproporex, caffeine, lidocaine, and cocaine. Separation was performed in <90 sec. The advantages of using C⁴D instead of traditional CE‐UV methods for in‐field analysis are also discussed.     

Chemical profiling of 3,4-methylenedioxymethamphetamine (MDMA) tablets seized in Hong Kong

During 2000-2001, the Government Laboratory of Hong Kong received over 600,000 ecstasy tablets in more than 2,600 cases. Using GC-MS or FTIR, the major amphetamine-type stimulants were identified, and the samples were categorized into four groups containing: (1) 3,4-methylenedioxymethamphetamine (MDMA), (2) methamphetamine (MA), (3) 3,4-methylenedioxyamphetamine (MDA), or (4) amphetamine. Our study revealed that in Hong Kong MDMA tablets have made up 98 and 71% of the total ecstasy tablets examined in 2000 and 2001, respectively. Among the MDMA cases, 613 cases involving a total of 123,776 tablets in 2001 were randomly selected, and their active ingredients, minor ingredients, and/or impurities were studied using GC-MS and HPLC. Based on the chemical profiles, and irrespective of their different physical characteristics, tablets obtained in different seizures could be determined as to whether or not they could have come from a common origin. The impurities detected in the MDMA tablets also served as excellent chemical markers from which plausible synthetic route(s) of the MDMA were inferred. Our study revealed that 3,4-methylenedioxyphenyl-2-propanone (MDP2P), 3,4-methylenedioxyphenyl-2-propanol (MDP), 3,4-methylenedioxy-N-methylbenzylamine (MDB), piperonal and N-formyl-3,4-methylenedioxymethamphetamine (N-formyl-MDMA) were the most common impurities detected in MDMA tablets seized in Hong Kong. The finding of the phosphate salt of MDMA is intriguing. Based on a presumptive color test, spectroscopic data (FTIR/ESI-MS) and the percentage of MDMA content in a purified phosphate salt of MDMA, the ratio of the phosphate to MDMA was determined to be 1:1, suggesting that the compound is a dihydrogen phosphate salt [i.e. (HMDMA)H2PO4].     

Development of microwave-assisted extraction procedure for organic impurity profiling of seized 3,4-methylenedioxymethamphetamine (MDMA)

Abstract: Organic impurity profiling of seized 3,4‐methylenedioxymethamphetamine (MDMA) tablets aims to link tablets to common production sources. Conventionally, organic impurities are extracted from tablets using a liquid–liquid extraction (LLE) procedure prior to analysis by gas chromatography–mass spectrometry (GC‐MS). In this research, the development of an alternative microwave‐assisted extraction/headspace solid‐phase microextraction (MAE/HS‐SPME) procedure is described. The optimal procedure used phosphate buffer (1 M, pH 8), with an HS‐SPME extraction temperature of 70°C for 40 min, using a divinylbenzene/Carboxen?/polydimethylsiloxane (DVB/CAR/PDMS) fiber. Impurities were extracted from seized MDMA exhibits using the MAE/HS‐SPME procedure, as well as HS‐SPME alone, and a conventional LLE procedure. The HS‐SPME procedure was deemed to be the most practical because of the affordability and need for less analyst involvement. Although the LLE was limited in the number of impurities extracted, the procedure is still useful for the extraction of less volatile impurities that are not extracted by HS‐SPME.     

Development of a Library Search‐Based Screening System for 3,4‐Methylenedioxymethamphetamine in Ecstasy Tablets Using a Portable Near‐Infrared Spectrometer

This is the first report on development of a library search‐based screening system for 3,4‐methylenedioxymethamphetamine (MDMA) in ecstasy tablets using a portable near‐infrared (NIR) spectrometer. The spectrum library consisted of spectra originating from standard substances as well as mixtures of MDMA hydrochloride (MDMA‐HCl) and diluents. The raw NIR spectra were mathematically pretreated, and then, a library search was performed using correlation coefficient. To enhance the discrimination ability, the wavelength used for the library search was limited. Mixtures of MDMA‐HCl and diluents were used to decide criteria to judge MDMA‐positive or MDMA‐negative. Confiscated MDMA tablets and medicinal tablets were used for performance check of the criteria. Twenty‐two of 27 MDMA tablets were truly judged as MDMA‐positive. Five false‐negative results may be caused by compounds not included in the library. No false‐positive results were obtained for medicinal tablets. This system will be a useful tool for on‐site screening of MDMA tablets.     

Methyl 3-[3',4'-(methylenedioxy)phenyl]-2-methyl glycidate: an ecstasy precursor seized in Sydney, Australia

Five 44 gallon drums labeled as glycidyl methacrylate were seized by the Australian Customs Service and the Australian Federal Police at Port Botany, Sydney, Australia, in December 2004. Each drum contained a white, semisolid substance that was initially suspected to be 3,4-methylenedioxymethylamphetamine (MDMA). Gas chromatography-mass spectroscopy (GC/MS) analysis demonstrated that the material was neither glycidyl methacrylate nor MDMA. Because intelligence sources employed by federal agents indicated that this material was in some way connected to MDMA production, suspicion fell on the various MDMA precursor chemicals. Using a number of techniques including proton nuclear magnetic resonance spectroscopy ((1)H NMR), carbon nuclear magnetic resonance spectroscopy ((13)C NMR), GC/MS, infrared spectroscopy, and total synthesis, the unknown substance was eventually identified as methyl 3-[3',4'(methylenedioxy)phenyl]-2-methyl glycidate. The substance was also subjected to a published hydrolysis and decarboxylation procedure and gave a high yield of the MDMA precursor chemical, 3,4-methylenedioxyphenyl-2-propanone, thereby establishing this material as a "precursor to a precursor."     

Interaction of 3,4-methylenedioxymethamphetamine and methamphetamine during metabolism by in vitro human metabolic enzymes and in rats

Illicit amphetamine-type stimulant (ATS) tablets commonly contain one or more active ingredients, which have hallucinogenic and/or stimulant effects. Because components such as 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (MA) in ATS tablets have similar chemical structures, they could be metabolized by common metabolic enzymes. To investigate potential metabolic interactions of ATS tablet components, we studied the in vitro metabolism of MDMA and MA using human metabolic enzymes. MDMA and MA were mainly metabolized by cytochrome P450 2D6 (CYP2D6) and mutually inhibited the production of their main metabolites. In vivo experiments were also performed using intravenous administration of MDMA, MA, or their mixture to rats. The plasma concentrations of MDMA and MA after co-administration were higher than those after administration of MDMA or MA alone. The results in this study imply that multiple components in ATS tablets can interact to mutually inhibit their metabolism and potentially enhance the toxicity of each component.     

Comparing Electronic News Media Reports of Potential Bioterrorism-Related Incidents Involving Unknown White Powder to Reports Received by the United States Centers for Disease Control and Prevention and the Federal Bureau of Investigation: U.S.A., 2009–2011

There have been periodic electronic news media reports of potential bioterrorism-related incidents involving unknown substances (often referred to as “white powder”) since the 2001 intentional dissemination of Bacillus anthracis through the U.S. Postal System. This study reviewed the number of unknown “white powder” incidents reported online by the electronic news media and compared them with unknown “white powder” incidents reported to the U.S. Centers for Disease Control and Prevention (CDC) and the U.S. Federal Bureau of Investigation (FBI) during a 2-year period from June 1, 2009 and May 31, 2011. Results identified 297 electronic news media reports, 538 CDC reports, and 384 FBI reports of unknown “white powder.” This study showed different unknown “white powder” incidents captured by each of the three sources. However, the authors could not determine the public health implications of this discordance.     

Screening tablets for DOB using surface-enhanced Raman spectroscopy

2,5,-Dimethoxy-4-bromoamphetamine (DOB) is of particular interest among the various "ecstasy" variants because there is an unusually long delay between consumption and effect, which dramatically increases the danger of accidental overdose in users. Screening for DOB in tablets is problematic because it is pharmacologically active at 0.2-3 mg, which is c. 50 times less than 3,4-methylenedioxy-N-methylamphetamine (MDMA) and makes it more difficult to detect in seized tablets using conventional spot tests. The normal Raman spectra of seized DOB tablets are dominated by the bands of the excipient with no evidence of the drug component. Here we report the first use of on-tablet surface-enhanced Raman spectroscopy (SERS) to enhance the signal from a low concentration drug. Raman studies (785-nm excitation) were carried on series of model DOB/lactose tablets (total mass c. 400 mg) containing between 1 mg and 15 microg of DOB and on seized DOB tablets. To generate surface-enhanced spectra, 5 microL of centrifuged silver colloid was dispensed onto the upper surface of the tablets, followed by 5 microL of 1.0 mol/dm(3) NaCl. The probe laser was directed onto the treated area and spectra accumulated for c. 20 sec (10 sec x 2). It was found that the enhancement of the DOB component in the model tablets containing 1 mg DOB/tablet and in the seized tablets tested was so large that their spectra were completely dominated by the vibrational bands of DOB with little or no contribution from the unenhanced lactose excipient. Indeed, the most intense DOB band was visible even in tablets containing just 15 microg of the drug. On-tablet surface-enhanced Raman spectroscopy is a simple method to distinguish between low dose DOB tablets and those with no active constituent. The fact that unique spectra are obtained allows identification of the drug while the lack of sample preparation and short signal accumulation times mean that the entire test can be carried out in <1 min.     

Analysis of ecstasy tablets: comparison of reflectance and transmittance near infrared spectroscopy

Calibration models for the quantitation of commonly used ecstasy substances have been developed using near infrared spectroscopy (NIR) in diffuse reflectance and in transmission mode by applying seized ecstasy tablets for model building and validation. The samples contained amphetamine, N-methyl-3,4-methylenedioxy-amphetamine (MDMA) and N-ethyl-3,4-methylenedioxy-amphetamine (MDE) in different concentrations. All tablets were analyzed using high performance liquid chromatography (HPLC) with diode array detection as reference method. We evaluated the performance of each NIR measurement method with regard to its ability to predict the content of each tablet with a low root mean square error of prediction (RMSEP). Best calibration models could be generated by using NIR measurement in transmittance mode with wavelength selection and 1/x-transformation of the raw data. The models build in reflectance mode showed higher RMSEPs using as data pretreatment, wavelength selection, 1/x-transformation and a second order Savitzky-Golay derivative with five point smoothing was applied to obtain the best models. To estimate the influence of inhomogeneities in the illegal tablets, a calibration of the destroyed, i.e. triturated samples was build and compared to the corresponding data of the whole tablets. The calibrations using these homogenized tablets showed lower RMSEPs. We can conclude that NIR analysis of ecstasy tablets in transmission mode is more suitable than measurement in diffuse reflectance to obtain quantification models for their active ingredients with regard to low errors of prediction. Inhomogeneities in the samples are equalized when measuring the tablets as powdered samples.     

Identification of 3,4-methylenedioxyamphetamine analogs encountered in clandestine tablets

Recently, 3,4-methylenedioxyamphetamine derivatives have been encountered in the Italian illicit market, mainly in form of tablets. Among this class of substances small modifications of the molecule may result in a wide range of derivatives and analogs some of which are not yet listed as controlled substances in the Italian schedules. Due to the structural similarity some of these molecules have a gas chromatographic behavior and mass spectra that only slightly differ. In the present work, an analytical strategy is proposed to achieve the identification of analogs within this class of molecules. In seized material sent by the Court of Law of Rome to our laboratories a number of tablets engraved with different symbols (e.g., `Dollar', `Fido Dido' and `Bomb') were submitted to analysis in order to establish whether they contained drugs of abuse. The analytical techniques employed for this purpose were UV spectrophotometry and thin-layer chromatography which provided information suggesting that the tablets contained a methylenedioxyamphetamine. Gas chromatography with flame ionization detection indicated that the main ingredient differed from the molecules of the same class already known. Finally, capillary gas chromatographic–mass spectrometric analysis of the native molecules and their pentafluoropropionic acid derivatives, performed with both, electron impact and chemical ionization, allowed the identification, in each tablet, of three molecules: the N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MDP-2-MB, MBDB), the 1-(3,4-methylenedioxyphenyl)-2-butanamine (MDP-2-B) and the N,N-dimethyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MDP-2-MMB).     

Isotope ratio mass spectrometry as a tool for forensic investigation (examples from recent studies).

The versatility of isotope ratio mass spectrometry is demonstrated by reference to diverse case studies. Variations in the natural isotopic composition of non-biological, organic materials are compared as a means by which samples may be associated or discriminated. These techniques may be used to augment or compliment conventional forensic methodologies. delta13C analysis was used to demonstrate that different masking tape had been recovered in two, apparently similar cases, involving the smuggling of money. Visually similar ecstasy tablets were compared by consideration of the delta13C and delta15N composition of MDMA extracted from the tablets. Although only a limited number of tablets were analysed, the isotopic similarity between two different seizures was sufficient to induce a guilty plea from a person suspected of possessing both. A combination of delta2H, delta13C, delta15N and delta18O together with GC-MS analyses were applied to small samples of seized heroin. Although GC-MS analysis indicated differences between the chemical composition of two of the heroin samples, isotopic analysis suggested similarities, which were confirmed by further delta2H, delta13C and delta18O isotopic analysis of the clingfilm in which the samples were wrapped.     

Evaluation of Suspected Counterfeit Pharmaceutical Tablets Declared to Contain Controlled Substances Using Handheld Raman Spectrometers

This study describes the performance of handheld Raman devices for determining whether suspect pharmaceutical tablets declared to contain controlled substances were consistent with authentic (CWA) or not consistent with authentic (NCWA) tablets using a simple, rapid, field-friendly method capable of being used by nonexperts. Twenty-five authentic products and 84 known NCWA tablets were examined using three “parent” devices for a total of 327 analyses. On average, the parent devices yielded a true pass rate of 100%, a true fail rate of 98.4%, a false pass rate of 1.6%, and a false fail rate of 0%. The methods/libraries were then transferred to 13 identical “daughter” devices, which were used to examine 10 suspect finished dosage forms in duplicate (six known NCWA tablets and four authentic tablets) for a total of 260 measurements. On average, the daughter devices had a true pass rate of 100%, a true fail rate of 95.5%, a false pass rate of 4.5%, and a false fail rate of 0.0%. These data demonstrate that the parent–daughter electronic transfer method was successful, which permits the ability to develop methods in the laboratory that can be seamlessly pushed out to field devices. The methods can then be used to (i) prioritize samples for additional testing using other more time-consuming laboratory-based techniques needed to detect and quantify active ingredients and (ii) help support the interdiction of dangerous tablets at ports of entry, thereby preventing them from reaching the supply chain.     

Heroin Overdose Deaths and Heroin Purity Between 1990 and 2000 in Istanbul,Turkey*

Abstract: Turkey has continuously experienced problems with abuse of, and addiction to, opium derivatives. In this study, we analyzed the relationship between heroin overdose deaths and the characteristics of seized opium derivatives. Data were gathered from the Council of Forensic Medicine of the Ministry of Justice in Istanbul from 1990 to 2000. There were 636 heroin‐related deaths during this period, 595 of which were classified as heroin overdose deaths. Mean crude and weighted heroin purities remained relatively constant and were calculated to be 46% (57–34%) and 51% (39–59%), respectively. The weight of heroin and the number of heroin seizures, but not the heroin purity, were significantly associated with the number of heroin‐related deaths. Prevention strategies are needed to reduce the number of deaths caused by overdoses in countries situated on drug trafficking routes. These strategies should focus on drug trafficking, by providing increased levels of, and support for, law enforcement, stopping the supply of precursor chemicals, and combating corruption among border officials.     

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.     

Availability of target odor compounds from seized ecstasy tablets for canine detection

The aim of this study was to compare seized samples of 3,4-methylenedioxy-N-methylamphetamine (MDMA) pills, used to train law enforcement detection canine teams, to determine what differences exist in the chemical makeup and headspace odor and their effect on detectability. MDMA solutions were analyzed by liquid chromatography-mass spectrometry. Analysis of these samples showed a wide variance of MDMA (8-25%). Headspace SPME-GC/MS analysis showed that several compounds such as 3,4-methylenedioxyphenylacetone and 1-(3,4-methylenedioxyphenyl)-2-propanol are common among these MDMA samples regardless of starting compound and synthesis procedure. However, differences, such as the level of the various methylenedioxy starting compounds, were shown to affect the overall outcome of canine detection, indicating the need for more than one MDMA training aid. Combinations of compounds such as the primary odor piperonal in conjunction with a secondary compound such as MDP-2-OH or isosafrole are recommended to maximize detection of different illicit MDMA samples.     

Is There a Relationship Between Street Heroin Purity and Drug‐Related Emergencies and/or Drug‐Related Deaths? An Analysis from Vienna,Austria*

This study examines the quality of street heroin seized in Vienna in 1999 and whether there was a relationship between the purity of street heroin and the number of heroin-related emergencies as well as the number of heroin-related deaths. Street heroin confiscated by the Viennese police, run-sheets of drug-related emergencies, and postmortem reports of drug-related deaths in Vienna in 1999 were analyzed. A total of 415 retail samples with a total weight of 128.02 g contained a median percentage of 6.5% diacetylmorphine (range: 0.0-47.0%). All the samples contained a diluent, mainly lactose, as well as adulterants, such as caffeine and/or paracetamol. During the study period, 75 heroin-related deaths and 387 heroin-related emergencies were registered in Vienna. Time-series analysis revealed no statistically significant relationship between the rate of heroin-related incidents and the diacetylmorphine concentration of street heroin samples confiscated in Vienna in 1999. The widely held belief that the number of heroin-related deaths could be explained simply through fluctuations in the purity of street heroin could not be substantiated, even though the results of this study do not rule out an association between the purity of heroin and heroin-related deaths/emergencies.