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].     

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.     

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.     

Chemical signature of ecstasy volatiles by comprehensive two-dimensional gas chromatography

A method for ecstasy volatiles 'signature' analysis based on two-dimensional gas chromatography separation and time-of-flight mass spectrometry detection (GC×GC-TOFMS) is presented. Organic impurity volatiles were extracted by head space solid phase microextraction (HS-SPME). The final column phase choice of the four different column combinations tested was a low-polarity 5% phenyl polysilphenylene-siloxane coupled with a polyethylene glycol phase, which best displayed the complex impurity profile. Second dimension ((2)D) retention time reproducibility was found to be about 1% RSD, and area reproducibility of SPME sampling was just over 5% RSD for compounds with S/N ratio of about 100. High similarity of TOFMS spectra of impurities was obtained against commercial MS libraries. 16 components from the two-dimensional profiles were selected for comparison of the 24 ecstasy tablets, most of which proved to be benzodioxole derived compounds. All tablets were correctly classified in eight groups according to their post-tabletting characteristics, when appropriate data pre-treatment was applied. Principal component analysis revealed clustering of samples according to the country of origin. Samples from Macedonia were elevated in N-formyl-MDMA and N-acetyl-MDMA while samples from Australia were elevated in 3,4-methylenedioxypropane and 3,4-methylenedioxyacetophenone. Furthermore, three components were found to be unique for one of the source countries. The additional separation of components on the (2)D column, increased response due to modulation, high acquisition rate with full mass spectra using TOFMS detection, and MS deconvolution extend the possibility of detecting additional markers and route-specific components, especially of low abundant, polar components.     

Hair analysis: self-reported use of "speed" and "ecstasy" compared with laboratory findings

Drug use histories were collected from 100 subjects recruited from the "dance scene" in and around Glasgow, Scotland. In addition, each subject donated a hair sample which was analyzed by gas chromatography/mass spectrometry (GC/MS) for amphetamine (AP), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MD MA) and 3,4-methylenedioxyethylamphetamine (MDEA). The hair samples were analyzed in two 6 cm segments or in full, ranging from 1.5 to 12 cm depending on the length of the hair. Approximately 10 mg of hair was ground to a fine powder before treatment with beta-glucuronidase/aryl sulfatase. A solid-phase extraction procedure was carried out followed by derivatization with pentafluoropropionic anhydride (PFPA). All extracts were analyzed by gas chromatography/mass spectrometry (GC/MS). Of the 139 segments analyzed, 77 (52.5%) were positive for at least one of the five amphetamines. The drug concentrations found in the hair were compared with the self-reported drug histories. A concordance of greater than 50% was found between the self-report data and levels detected in hair. However, no correlation was found between the reported number of "ecstasy" tablets consumed and the drug levels detected in hair. An increase in the average drug levels measured was observed from low to high use (number of "ecstasy" tablets/month). A large number of false negatives and a low number of false positives were observed.     

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.     

"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.     

Ecstasy--deadly risk even outside rave parties

Fatalities due to 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") are rare in Austria, although the use of designer drugs has become quite common. This is the first published case of a fatal MDMA intoxication in Austria. A 19-year-old girl died after the consumption of ecstasy tablets in the apartment of a friend. Blood analysis gave a concentration of MDMA as 3.8 mg/L and traces of its metabolite MDA. Cannabinoids were found as well. This case shows that the consumption of MDMA, without physical stress, can lead to death.     

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.     

Screening experiments of ecstasy street samples using near infrared spectroscopy

Twelve different sets of confiscated ecstasy samples were analysed applying both near infrared spectroscopy in reflectance mode (1100-2500 nm) and high-performance liquid chromatography (HPLC). The sets showed a large variance in composition. A calibration data set was generated based on the theory of factorial designs. It contained 221 N-methyl-3,4-methylenedioxyamphetamine (MDMA) samples, 167 N-ethyl-3,4-methylenedioxyamphetamine (MDE), 111 amphetamine and 106 samples without a controlled substance, which will be called placebo samples thereafter. From this data set, PLS-1 models were calculated and were successfully applied for validation of various external laboratory test sets. The transferability of these results to confiscated tablets is demonstrated here. It is shown that differentiation into placebo, amphetamine and ecstasy samples is possible. Analysis of intact tablets is practicable. However, more reliable results are obtained from pulverised samples. This is due to ill-defined production procedures. The use of mathematically pretreated spectra improves the prediction quality of all the PLS-1 models studied. It is possible to improve discrimination between MDE and MDMA with the help of a second model based on raw spectra. Alternative strategies are briefly discussed.     

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.     

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.     

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.     

Seizures of Clandestinely Produced Tablets in Santa Catarina,Brazil: The Increase in NPS from 2011 to 2017

Ecstasy is the name given to a large group of substances known as “club drugs” traded in the form of tablets, powder and liquid that present a varied composition, including mainly 3,4-methylenedioxymethamphetamine (MDMA) and analogous substances, in addition to the growing presence of new psychoactive substances. Based on this, clandestinely produced tablets (“ecstasy tablets”) seized by police in Santa Catarina in the period from 2011 to 2017 were analyzed. During the study period, 3472 seizures occurred, which resulted in total 498,443 tablets seized. Seventy nine substances were identified. In the year 2011, about 90% of the tablets contained MDMA. This number decreased to 66.6% in 2017. On the other hand, there was an increase in the number of tablets that mainly contained synthetic cathinones, as well as tryptamine and piperazine derivatives. Police seizures in the metropolitan region of Florianópolis and on the coast prevailed over the rest of the state.     

论香港与内地法院间对判决的相互承认及执行

在香港回归以前,由于国内判决只享有"外国判决"的地位,因此在香港只能按照普通程序执行。香港回归以后,根据《外地判决(交互强制执行)条例》所订登记制度的规定,却不能适用于内地判决。基于此,讨论了在大陆和香港两套法律体制并存的情况下,怎样承认及执行双方的民事判决,以及由此所遇到的困难和产生的问题。深入研究了最高人民法院的《关于内地与香港特别行政区法院相互委托送达民商事司法文书的安排》以及最高人民法院与香港律政司签署的《关于内地与香港特别行政区相互执行仲裁裁决的安排》两份文件,并通过与其他国家处理国内区际司法协助的做法以及香港回归以前所适用的国际条款作比较,推导和分析了回归后国内与香港特区之间在司法协助问题上所应遵循的一般原则。     

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.     

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.     

Use of MDA (the "love drug") and methamphetamine in Toronto by unsuspecting users of ecstasy (MDMA)

It has recently been reported that purity of illicit tablets of ecstasy (MDMA) is now high. Our objective was to confirm whether hair of drug users, who request only ecstasy from their supplier, contains MDMA in the absence of other drugs. GC-MS analysis of scalp hair segments disclosed the presence of MDMA in 19 of 21 subjects and amphetamine/methamphetamine in eight subjects. Surprisingly, seven subjects had hair levels of the MDMA metabolite, MDA, equal to or greater than those of MDMA, suggesting use of MDA in addition to that of MDMA. These amphetamine derivatives might be included by clandestine laboratories to enhance effects of the drug cocktail or because of a perception that MDA synthesis might be simpler than that of MDMA. Drug users and investigators examining possible brain neurotoxic effects of MDMA need to consider that "ecstasy" tablets can contain MDA and methamphetamine despite no demand for the drugs.     

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.     

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.