Ecstasy Samples Research Articles

A compact Fourier-transform near-infrared spectrophotometer and chemometrics for characterizing a comprehensive set of seized ecstasy samples

A comprehensive data set of ecstasy samples containing MDMA (N-methyl-3,4-methylenedioxyamphetamine) and MDA (3,4-methylenedioxyamphetamine) seized by the Brazilian Federal Police was characterized using spectral data obtained by a compact, low-cost, near-infrared Fourier-transform based spectrophotometer. Qualitative and quantitative characterization was accomplished using soft independent modeling of class analogy (SIMCA), linear discriminant analysis (LDA) classification, discriminating partial least square (PLS-DA), and regression models based on partial least square (PLS). By applying chemometric analysis, a protocol can be proposed for the in-field screening of seized ecstasy samples. The validation led to an efficiency superior to 96 % for ecstasy classification and estimating total actives, MDMA, and MDA content in the samples with a root mean square error of validation of 4.4, 4.2, and 2.7 % (m/m), respectively. The feasibility and drawbacks of the NIR technology applied to ecstasy characterization and the compromise between false positives and false negatives rate achieved by the classification models are discussed and a new approach to improve the classification robustness was proposed considering the forensic context.

Validated green phenyl reversed-phase LC method using ethanol to determine MDMA in seized ecstasy tablets

3,4-Methylenedioxymethamphetamine (MDMA) is a popular illicit drug. Given its adverse effects, the growing abuse of MDMA worldwide, and the need for forensic chemistry methods that minimize environmental issues, here we report a green approach for quantitative MDMA analysis in ecstasy tablets based on phenyl reversed-phase liquid-chromatography coupled to a diode-array detector. Water with 0.1% formic acid (pH adjusted to 5.00 with ammonium hydroxide) and ethanol (85:15, v/v) was employed as the mobile phase. The method showed good analytical performance in terms of linearity (0.0031–0.1 mg mL−1, R 2 = 0.9998), precision (1.26–7.79%), accuracy (93.5–107.7%), and recovery (96.6–100.6%). The limits of detection and quantification were 0.0007 and 0.0031 mg mL−1, respectively. The MDMA purity ranged from 14.7% to 35.1% (m/m). Additionally, greenness assessment using an eco-scale metric provided a score. The results indicated that the simultaneous use of ethanol and phenyl-bonded phase provides high selectivity and is suitable and reliable for routine analysis of seized ecstasy samples, constituting a powerful alternative to expensive mass spectrometer-based liquid chromatography and common reversed-phase columns.

Development of an Electrochemical Method Employing Carbon Screen-Printed Electrodes (C-SPEs) for Detection and Study of MDMA Redox Process

According to ONU reports, the use of abusive drugs has increased, requiring sensitive techniques for the detection of these substances [1]. This interconnection brings a scenario in which chemical detection of narcotics by conventional, low-cost methods is necessary for drug control. Thus, instrumental analytical techniques appear as indispensable tools for analysis of unknown substances in the forensic field because of their ability to bring low detection limits and selectivity. Thus, the carbon Screen-Printed electrode was elected to develop an electroanalytical method and to study the electrochemical behavior of MDMA for its drug detection potential, low cost, and easy applicability. So, our objective was to develop an electrochemical method with Carbon Screen-Printed electrodes for MDMA detection and study of its redox processes.Palmsens ® Screen-Printed electrodes were utilized in this work. The behavior de the redox processes of MDMA were carried out with a 1.3×10-3 mol L-1 solution in 0.1 mol L-1 phosphate buffer (PBS) at 2.0, 4.0, 6.0, 8.0, 9.0, and 10.0 pH, since MDMA structure can be protonated at the amino group and turns easier the π orbitals delocalization [2]. The MDMA quantification method development utilized PBS 0.1 M at pH 9.0. The absence of cathodic peaks narrowed the sweeps just as anodic. Thus, Cyclic Voltammetry (CV), Linear Sweep Stripping Voltammetry (LSSV), Differential Pulse Voltammetry (DPSV), and Square Wave Stripping Voltammetry (SWSV) were employed. Adulterants such as caffeine (0.31 mmol L-1), lidocaine (0.25 mmol L-1), acetaminophen (0.66 mmol L-1), AAS (0.28 mmol L-1) and phenacetin (0.56 mmol L-1) were utilized to observe possible interference in the MDMA detection.The scan rate study indicated that the anodic peak currents are directly proportional the square root of the scan speed in the range from 5 to 100 mV s-1, indicating that the electron transfer reaction of the MDMA on the electrode is diffusion controlled, as predicted by Randles-Sevcik equation. Using carbon SPE, the influence on the change of electrolyte pH through CV was evaluated. Its It was observed that the best currents are obtained at pH 9.0 with supporting electrolyte in 0.1 mol L-1 concentration. For the development of the analytical method, the investigation of the redox processes of MDMA were obtained with LSSV, SWSV and DPSV. The LSSV modality presented the best peak resolution (1.92 ×10-4 AV-1) when compared to SWSV (9.26 × 10-5 AV-1) and DPSV (1.7 × 10-5 AV-1) ). Using LSSV, the equilibrium time parameter was optimized (2.5 to 80 s), such as MDMA preconcentration potential (-1 to 1 V), electrodeposition time (20 to 600 s), and scan speed (5 to 100 mV.s-1) in the potential range from 0.2 to 1.2 V. The best oxidation currents of MDMA were observed at 10 s equilibrium time, -0.5 V preconcentration potential, and electrodeposition time of 20s, using ν = 20 mV.s-1. The merit figures for the developed method were evaluated through analytical curves. PBS solutions at pH 9.0 were prepared with MDMA concentrations ranging from 8.0×10-5 to 1.3×10-3 mol L-1. The analytical curve showed a linear range in this concentration range with detection limit of 7.3×10-5 mol L-1, amperometric sensitivity of 1.43×10-2 A.mol-1.L and linear correlation coefficient of 0.998. Just lidocaine and phenacetin showed electroactivity in this method, but did not demonstrate interference at MDMA response. The results indicated that the analytical method proposed using linear sweep stripping voltammetry showed good analytical performance indicating that the proposed electrode are able to the detection and determination of MDMA in ecstasy samples. Acknowledgements FAPESP (process n°2019/04439-3, and 2016/23825-3) and CAPES (Pro-Forenses 25/2014).

Statistical Assessment using Chemical Profiling of Ecstasy Samples Seized in Turkey

The physical and chemical characteristics of ecstasy have been extensively investigated for many years, but establishing links between the seizures, determining their origin, and monitoring the abuse traffic of this drug through analytical and statistical methods have only recently become a research topic. In this study, the ecstasy samples seized by the Turkish National Police were analyzed to obtain their chemical characteristics. In the chemical profiling, 17 elements and main organic constituents such as MDMA and amphetamine were identified in 18 ecstasy samples. The chemical profiles of the seizures were also statistically assessed using hierarchical cluster, principal component and correlation analyses. The Ba, Cu, Co, Rb and Pb elements indicated that the seizures came from the same network, and therefore, these elements can be used to obtain the origin of the seizures and monitor the abuse traffic of ecstasy.

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.

Establishing chemical profiling for ecstasy tablets based on trace element levels and support vector machine

Ecstasy is an amphetamine-type substance that belongs to a popular group of illicit drugs known as “club drugs” whose consumption is rising in Brazil. The effects caused by this substance in the human organism are mainly psychological, including hallucinations, euphoria and other stimulant effects. The distribution of this drug is illegal, and effective strategies are required in order to detain its growth. One possible way to obtain useful information on ecstasy trafficking routes, sources of supply, clandestine laboratories and synthetic protocols is by its chemical components. In this paper, we present a data mining and predictive analysis for ecstasy tablets seized in two cities of Sao Paulo state (Brazil), Campinas and Ribeirao Preto, based on their chemical profile. We use the concentrations of 25 elements determined in the ecstasy samples by ICP-MS as our descriptive variables. We develop classification models based on support vector machines capable of predicting in which of the two cities an arbitrary ecstasy sample was most likely to have been seized. Our best model achieved a 81.59% prediction accuracy. The F-score measure shows that Se, Mo and Mg are the most significant elements that differentiate the samples from the two cities, and they alone are capable of yielding an SVM model which achieved the highest prediction accuracy.

Developing electrodes chemically modified with cucurbit[6]uril to detect 3,4-methylenedioxymethamphetamine (MDMA) by voltammetry

This study aimed to develop an electrode chemically modified with cucurbit[6]uril to detect 3,4-methylenedioxymethamphetamine (MDMA), the main active principle of ecstasy samples, by voltammetry.We modified the electrode surface with a film containing cucurbit[6]uril, Nafion, and methanol, using the dip coating or the spin coating technique. During analysis, we employed an electrochemical cell with a conventional three-electrode system and KCl solution (0.1molL−1) as the supporting electrolyte. We conducted cyclic voltammetry at concentrations ranging from 4.2×10−6 to 4.8×10−5molL−1. We also accomplished scanning electron microscopy, to investigate the structural behavior of the film that originated on the electrode surface.We obtained the following results when we used dip coating to prepare the modified electrode: standard deviation (SD)=0.024μA, limit of detection (LOD)=3.5μmolL−1, limit of quantification (LOQ)=11.7μmolL−1, and amperometric sensitivity (m)=20.9×103μALmol−1. As for spin coating, we obtained SD=0.024μA, LOD=2.7μmolL−1, LOQ=9.1μmolL−1 and m=25.9×103μAmolL−1. These are very promising data: the modified electrode is more sensitive than the conventional glassy carbon electrode under the studied experimental conditions.

Chemical profiling of ecstasy recovered from around Jakarta by High Performance Thin Layer Chromatography (HPTLC)-densitometry

In the current study, we identify the use of HPTLC-densitometry and cluster analysis of major substances in profiling seized ecstasy tablets from around Jakarta. One hundred milligrams of a homogenized drug sample was dissolved in 5ml of pH 10.5 phosphate buffer solution and extracted with 1ml toluene. The two micro litter of extract spotted on two HPTLC Si GF 254 (20×10cm) plates, then eluted on twin chamber with TB (cyclohexane:toluene:diethylamine 75+15+5 v/v) and TAEA (toluene:acetone-ethanol:conc.ammonia, 45+45+7+3 v/v) separately. The spots were scanned by TLC-Scanner 3 Camag at 210nm. The UV-in situ spectrum of each peaks was scanned at 190–400nm. Corrected hRf-value (hRfc) and insitu spectrum of chromatogram were used to confirm the identity of unknown drugs. Clustering of chromatograms of extracted ecstasy samples was based on their hRfc and AUC of peak. This method was best implemented for street drug identification and grouping a sample into a cluster based on their chemical characteristic.

Solid phase extraction for GC-FID determination of 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and methamphetamine (MA) in human urine

A simple solid phase extraction method was developed for estimating the amounts of 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and methamphetamine (MA) in urine by using the GC-FID technique. The urine sample was alkalinized prior to undergoing solid phase extraction using Oasis HLB®. A 5% methanol-water mixture containing 2% ammonium hydroxide was used for washing, whereas a 70% methanol-water mixture containing 2% acetic acid was used for elution. The compounds were analyzed using the standard GC-FID conditions previously established for ecstasy samples, i.e., column: CP-SIL 24 CB WCOT (30 m × 0.32 mm i.d., 0.25 μm film thickness); carrier gas: N2 (2.6 mL/min); injector temperature: 290°C; detector temperature: 300°C; oven temperature: initial 80°C, final 270°C (1 min), ramp rate 20°C/min. Validation demonstrated the linearity of the calibration curves between 1 and 20 μg/mL (r > 0.99) for all analytes. The precisions (% RSD) were approximately 3–17%, 6–16% and 7–17% for MDMA, MDA and MA, respectively. The accuracies (% DEV) were (−)17-(+)5%, (−)18-(+)15% and (−)18-(+)0.6% for MDMA, MDA and MA, respectively. The recovery ranged from 80 to 107% and the lower limit of quantification (LLOQ) was 1 μg/mL. The method was successfully applied to determine the levels of these compounds in the urine of drug abuse suspects.

Analysis of heavy metals in ecstasy tablets by electrochemical methods

Trace amounts of heavy metals have been analysed by electrochemical techniques in ecstasy tablets obtained from different police seizures in Spain. Lead, cadmium, copper and zinc were determined by differential-pulse anodic stripping voltammetry at a hanging mercury drop electrode, whereas nickel and cobalt were determined by adsorptive differential-pulse cathodic stripping voltammetry from their dimethylglyoxime complexes, M(DMG)2. The performance of the procedure was compared with electrothermal atomic absorption spectrometry. The procedure was applied to the determination of these elements in nine ecstasy samples, finding that Zn is the element present in the highest concentration, ranging from 0.3 to 200 mg kg−1, Ni, Cu appear below 15 mg kg−1 and Pb below 8 mg kg−1, while Cd and Co levels were always lower than 0.51 mg kg−1.

Determination of mercury and arsenic in ecstasy tablets by electrochemical methods

Mercury and arsenic concentrations were determined in ecstasy tablets, which were obtained from different police seizures in Spain, by electrochemical techniques; mercury by differential pulse anodic stripping voltammetry with a rotating gold disk electrode, and arsenic by cathodic stripping voltammetry in the differential pulse mode with a hanging mercury drop electrode. The performance of the procedures was compared with cold-vapor atomic absorption spectrometry for mercury, and with electrothermal atomic absorption spectrometry for arsenic. The procedures were applied to the determination of both elements in nine ecstasy samples; mercury was the element present in higher concentrations, ranging from 0.05 to 1.23 mg/kg, while the range of arsenic concentrations was 0.04–0.49 mg/kg. The described electrochemical techniques for determination of mercury and arsenic in ecstasy tablets should be useful for impurity profiling in forensic analysis practice, because of their low costs and high sensitivity.

Sugar and fatty acid analysis in ecstasy tablets

Sugars and stearates (composed of fatty acids) are both frequent components used in the production of ecstasy tablets. Their analysis can therefore provide supplementary information useful for drug intelligence. Links established using these substances would be very significant as they should give us information about the manufacturer of the tablets. Two methods have been developed for the analysis of sugars and fatty acids by GC–MS and were applied to 109 ecstasy tablets. Characterisation of the samples should allow the differentiation of a certain number of them and furthermore their classification into groups. This is obtained by analysing the raw data using chemometric methods. Several pre-treatments have been tested together with six similarity measures on a small number of ecstasy samples in order to determine which combination would best characterise one ecstasy sample and differentiate it from the others at the same time. Normalisation followed by the fourth square and applied together with the squared cosine function appeared to give the best results and has been applied to all samples. The correlation values obtained of each sample with all others express the probability of a presence of a link between two samples. In order to verify the signification of these values, and thus of a link, all samples have been compared considering the data visually according to three selected criterions. The 109 examined samples could be divided into 67 groups, with 43 of them containing only one sample. Considering the distribution of their correlation values, sample pairs showing a value below 0.23 can be considered as linked. As the excipients are necessarily related to the blending, which also includes the active substance, and variation in the excipient content has been proven by the grouping of the samples, a low similarity value does indicate a link with regard to the producer. In conclusion, it appears that the result obtained with the excipients is certainly very valuable, but all other available information has to be taken into account as well before making any conclusions.

Pharmacological Characterization of Ecstasy Synthesis Byproducts with Recombinant Human Monoamine Transporters

Ecstasy samples often contain byproducts of the illegal, uncontrolled synthesis of N-methyl-3,4-methylenedioxy-amphetamine or 3,4-methylenedioxymethamphetamine (MDMA). MDMA and eight chemically defined byproducts of MDMA synthesis were investigated for their interaction with the primary sites of action of MDMA, namely the human plasmalemmal monamine transporters for norepinephrine, serotonin, and dopamine [(norepinephrine transporter (NET), serotonin transporter (SERT), and dopamine transporter (DAT)]. SK-N-MC neuroblastoma and human embryonic kidney cells stably transfected with the transporter cDNA were used for uptake and release experiments. Two of the eight compounds, 1,3-bis (3,4-methylenedioxyphenyl)-2-propanamine (12) and N-formyl-1,3-bis (3,4-methylenedioxyphenyl)-prop-2-yl-amine (13) had uptake inhibitory potencies with IC50 values in the low micromolar range similar to MDMA. Compounds with nitro instead of amino groups and a phenylethenyl instead of a phenylethyl structure or a formamide or acetamide modification had IC50 values beyond 100 microM. MDMA, 12, and 13 were examined for induction of carrier-mediated release by superfusion of transporter expressing cells preloaded with the metabolically inert transporter substrate [3H]1-methyl-4-phenylpyridinium. MDMA induced release mediated by NET, SERT, or DAT with EC50 values of 0.64, 1.12, and 3.24 microM, respectively. 12 weakly released from NET- and SERT-expressing cells with maximum effects less than one-tenth of that of MDMA and did not release from DAT cells. 13 had no releasing activity. 12 and 13 inhibited release induced by MDMA, and the concentration dependence of this effect correlated with their uptake inhibitory potency at the various transporters. These results do not support a neurotoxic potential of the examined ecstasy synthesis byproducts and provide interesting structure-activity relationships on the transporters.

Structure elucidation of nanogram quantities of unknown designer drugs based on phenylalkylamine derivates by ion trap multiple mass spectrometry.

Multiple mass spectra (MS(1) to MS(6)) of 55 phenylalkylamine derivatives were recorded with ion-trap mass spectrometry employing electrospray (ESI) and atmospheric pressure chemical ionization (APCI). Fragmentation patterns were studied in detail and a generally applicable scheme was established for elucidation of the structures of phenylalkylamine derivatives. HPLC combined with ion-trap multiple mass spectrometry was used to identify the structure of reaction by-products in ecstasy samples from the "black" market. Low nanogram amounts were sufficient for on-line HPLC-MS(n) structure elucidation of unknowns.

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.

Identification of ecstasy in complex matrices using near-infrared spectroscopy

A strategy was developed for the non-destructive identification of illicit ecstasy samples. Examinations were restricted to N-methyl-3,4-methylendioxyamphetamine (MDMA), N-ethyl-3,4-methylendioxyamphetamine (MDE) and amphetamine, which are the main substances abused in ecstasy tablets. The samples were analysed applying near-infrared (NIR) spectroscopy (1100–2500 nm) in reflectance mode. The experimental design was used to extract maximum information from a minimum number of experiments. A calibration data set containing 497 powdered MDMA, MDE, amphetamine and placebo samples was established. Either raw or second derivative spectra were used to calculate the PLS-1 and PLS-2 models, respectively. The prediction values of eight different independent test sets were employed for model validation. The best results were obtained using the PLS-2 model based on second derivative spectra. It is shown that discrimination of the three substances in complex tablet matrices is possible. Variation of the composition in the calibration set is sufficient for prediction of samples containing either these drugs in combination with unknown excipients or only placebo samples. NIR spectroscopy offers an excellent possibility for fast and non-destructive identification of ecstasy drugs.