Drug Laboratory Research Articles

Analysis of D- and L- Isomers of (Meth)amphetamine in Human K2EDTA Plasma

Methamphetamine and its metabolite amphetamine are frequently abused drugs. Whether obtained legally or from clandestine laboratories it is of relevance to determine the chiral makeup of these drugs for investigative purpose. Although urine and oral fluid matrices are commonly offered, less available to independent laboratories are techniques to verify dextro (D-) or levo (L-) (meth)amphetamine from human K2EDTA plasma. This paper outlines the development and validation of a method that includes the addition of internal standard and a two-step liquid-liquid extraction to remove the analytes from human K2EDTA plasma by triple quadrupole mass spectrometry (LC-MS/MS). The assay was validated according to the United States Food and Drug Administration and College of American Pathologists guidelines, including assessment of the following parameters in plasma validation samples: linear range, limit of detection, lower limit of quantitation, matrix effects, inter- and intra-day assay precision and accuracy, carry over, linearity of dilution, matrix effects and stability. The outcome is a validated and reliable method for the determination of D- and L- isomer concentration of meth(amphetamine) human plasma samples that can be easily adopted by independent clinical laboratories.

The influence of water of crystallization in NIR-based MDMA·HCl detection

The large numbers of 3,4-methylenedioxy-N-methylamphetamine (MDMA) formulations encountered by the police and border security necessitates the need for safe, rapid and reliable tests to be performed on-site. Near-infrared (NIR) spectroscopy is a promising technique for on-scene illicit-drug detection because of its rapid analysis, non-invasive nature, broad scope to detect various substances, and small-sized sensors suitable for portable operation. The NIR spectrum of MDMA shows an intriguing, intense peak at ∼2000 nm that was found characteristic for MDMA within a large set of drugs and drug-related substances. Herein, we show that this peak can be attributed to water molecules of crystallization in the MDMA lattice. Drying experiments showed that both an anhydrous and hydrated form of MDMA·HCl exists with significantly different NIR spectra. At ambient conditions, the anhydrous form converted back to the hydrated form within 2 months. Our data analysis model was able to identify MDMA·HCl in mixtures of both forms. Assessment of seized casework materials showed that the majority of MDMA·HCl in The Netherlands is of the hydrated type. This is explained by the use of water-containing concentrated hydrochloric acid in the final conversion step of MDMA-base to the hydrochloride salt in clandestine laboratories. These findings provide insight in the challenges associated with NIR-based identification of drugs that may appear in various crystalline forms. Awareness on the existence of these forms and the consequences of library and data-model design to cope with this phenomenon will increase the robustness of on-site NIR-based drug detection.

Methamphetamine Lab Explosion: A Pediatric Emergency Medicine Case.

Children exposed to the manufacture of illegal drugs are at risk for multiple medical problems. Providers need to be able to recognize and manage the complications from these exposures because early intervention can be crucial to decreasing morbidity and mortality. In this simulation case, a 3-year-old patient is brought to the emergency department (ED) after a house fire due to a methamphetamine lab explosion. The goals of this case are to provide the learners with the training and opportunity to manage a toxic chemical exposure by applying principles and methods of decontamination, and to manage an inhalational injury with rapidly progressive airway edema. These events being rare, this simulation gives learners crucial experience with a high-stakes medical condition.

Electrochemical sensing of amphetamine-type stimulants (pre)-precursors to fight against the illicit production of synthetic drugs

The illicit drug precursor market for the manufacture of amphetamine-type stimulants (ATS), mainly amphetamine, methamphetamine and methylenedioxymethamphetamine (MDMA), has emerged quickly in the last years. The evidence of a more complex and sophisticated drug market underlines the pressing need for new on-site methods to quickly detect precursors of synthetic drugs, with electrochemical analysis as a promising technique. Herein, the electrochemical fingerprints of ten common ATS precursors-3-oxo-2-phenylbutanenitrile (APAAN), 3-oxo-2-phenylbutanamide (APAA), methyl 3-oxo-2-phenylbutanoate (MAPA), benzyl methyl ketone (BMK), 1-(1,3-benzodioxol-5-yl)propan-2-one (PMK), ephedrine, pseudoephedrine, safrole, sassafras oil and piperonal- are reported for the first time. The electrochemical screening disclosed the redox inactivity of BMK, which is an essential starting material for the production of ATS. Therefore, the local derivatization of BMK at an electrode surface by reductive amination is presented as a feasible solution to enrich its electrochemical fingerprint. To prove that, the resulting mixture was analyzed using a set of chromatographic techniques to understand the reaction mechanism and to identify possible electrochemical active products. Two reaction products (i.e. methamphetamine and 1-phenylpropan-2-ol) were found and characterized using mass spectrometry and electrochemical methods. Subsequently, the optimization of the reaction parameters was carefully addressed to set the portable electrochemical sensing strategy. Ultimately, the analysis concept was validated for the qualitative identification of ATS precursors in seizures from a forensic institute. Overall, the electrochemical approach demonstrates to be a useful and affordable analytical tool for the early identification of ATS precursors to prevent trafficking and drug manufacture in clandestine laboratories.

Trends of clandestine laboratories manufacturing methamphetamine in New Zealand between 2009-2021: Evolution, enforcement, legislative, and COVID-19 effects.

The most common method of domestic methamphetamine manufacture encountered in New Zealand is the hydrogen iodide (HI) reduction of pseudoephedrine/ephedrine. While the overall method used to manufacture methamphetamine has remained consistent, the processes and chemicals utilized have evolved. Understanding the reason for any changes to methamphetamine manufacturing trends can assist jurisdictions with predicting the potential effects of enforcement and legislative initiatives. This paper presents data and trends amassed from suspected clandestine laboratories, associated with the manufacture of methamphetamine, in New Zealand between 2009 and 2021, along with data on methamphetamine, pseudoephedrine, and ephedrine seizures at the border. The data have shown that clandestine manufacturers in New Zealand have evolved the methamphetamine manufacturing process over the years. These changes in trends can largely be attributed to various enforcement and legislative effects and the COVID-19 pandemic response. Effects that enforcement, legislation, and the COVID-19 pandemic response may have had on the precursors, chemicals and equipment encountered are discussed.

Passive exposure to cocaine on a professional level: Importance of considering relevant interpretation parameters

The aim of this study was to evaluate the extend of passive exposure in hair from professionals working in contact with cocaine seizures, considering cleaning procedures, hair segmentation and interpretation recommendations from the consensus on drug hair testing [ https://soht.org/images/pdf/Consensus_DoA_2021.pdf ] and from recent literature. In forensic casework where hair analysis is requested, forensic experts have to answer the question if the drug concentrations found are due to an active use or rather a passive contamination. In this preliminary study, the impact of (chronic) passive exposure to cocaine was evaluated by analyzing hair from subjects in contact with cocaine on a professional level (laboratory technicians and law enforcement dealing with clandestine laboratories). The level of exposure was depending on specific tasks from dismantling of clandestine laboratories (high) to treatment of large quantities of drug samples (medium) to the analysis of few grams of those samples in the laboratory (low). Head hair was collected from 7 volunteers. A total of 19 samples were collected at different time periods [number of samples ( n ): high = 4; medium: n = 9; low: n = 6]. Hair samples were cut in segments, decontaminated with our routine method using dichloromethane, water and methanol, and extracted [Ramirez Fernandez MdM, Di Fazio V, Wille SM, Kummer N, Samyn N. J Chromatogr B Analyt Technol Biomed Life Sci 2014;965:7–18.]. The last wash was also kept for analysis. An extended washing procedure was also evaluated. The samples were analysed with a routine method for cocaine, benzoylecgonine, norcocaine, cocaethylene, m-OH-benzoylecgonine, and methylecgonine. Five test subjects also provided us with a urine sample two days after the cocaine manipulation. The results for median (pg/mg) and minimum and maximum value concentrations in hair according to the level of exposure were as follows: – (A) cocaine in hair; – (B) ratio benzoylecgonine/cocaine in hair; – (C) ratio norcocaine/cocaine in hair; – (D) ratio cocaine hair/wash: – high: A (682; 36–7045); B: 0.07; (0.05–0.11); C: 0.023; (0.009–0.031); D: 2.23; (0.5–31), – medium: A (92; < LOQ(32)-489); B (0,92;0.13–5.49); C: < LOQ (< LOQ); D (9; 6.7–10,5), – low: A [56; < LOQ(32)-189]; B [0.16; 0,16–0.16 (only one value)]; C: < LOQ (< LOQ); D (1.51; 1.0–4.7). Increasing concentrations of cocaine were detected from root to tip when longhair strands were analysed, both in hair and in the washes. For subjects with high exposure, concentrations in hair above recommended cut-offs for cocaine (> 500 pg/mg) with relatively high concentrations of benzoylecgonine (up to 716 pg/mg) and norcocaine (up to 342 pg/mg) were detected. In cases with medium and low exposure, benzoylecgonine and norcocaine were negative or detected at traces level and all hair samples were negative for cocaethylene, methylecgonine, and m-OH-benzoylecgonine (LOQ 1–3 pg/mg). Regarding the analysis of the washing, recent contaminated hair samples presented the highest cocaine concentrations in the washes (> 10%). Extended washing procedures did not improve the interpretation of the results. All urine samples were all negative according European Workplace Drug testing cut-offs (100 ng/mL) proving no recent use. The obtained results show a good correlation between the level of passive exposure to cocaine and the concentrations in hair. This preliminary study demonstrates that the cut-off values for cocaine should not be applied as a sole criterion. Following other parameters are mandatory to be considered too: case context, cut-off-values, cocaine versus metabolites, hair versus washing concentrations ratios, and the presence of more specific metabolites such as cocaethylene, and hydroxy metabolites.

Cocaine derivatives–synthesis, analytical characterization and evaluation of their cross reactivity in immunochemical assays

Synthetic cocaine derivatives are currently marketed on various internet websites as legal cocaine alternatives. These psychoactive substances include phenyltropanes (troparil, dichloropane, RTI-55), 1,4-dialkyl piperazines, phenyl piperidines, benztropines, and dimethocaine. Although they have been sold as “research chemicals” for more than a decade, they have not been studied systematically. Their consumption evades forensic-toxicological perception through the absence of specific identification methods. For a holistic forensic investigation of synthetic cocaine derivatives, the availability of reference compounds is a limiting factor. Moreover, synthetic side products, stereoisomers, degradation products, or deuterated references have not been isolated and characterized. Therefore, the immunochemical cross-reactivity of cocaine derivatives will be investigated after their synthesis and analytical characterization. Diverse phenyltropanes, e.g., troparil, dichloropane, and phenyl piperidines, were synthesized using documented methods. In addition, stereoisomers and deuterated references as well as metabolites were also produced. The reactions were carefully monitored, and all products were purified and characterized with NMR spectroscopy, high-resolution mass spectrometry, and polarimetry. In addition, the synthesized substances and their metabolites, which are structurally closely related to cocaine and benzoylecgonine, were tested in a CEDIA cocaine assay to evaluate their cross-reactivity. In cooperation with the Institute of Pharmacy and Molecular Biotechnology in Heidelberg, the aimed phenyltropanes and phenyl piperidines were successfully synthesized and analytically characterized. All synthesized compounds were tested in the CEDIA cocaine assay in concentrations of 100 and 1000 ng/mL. Altogether none of the compounds showed significant cross-reactivity to create a false-positive result. The availability of reference compounds is often a bottleneck of research in forensic chemistry and toxicology. Therefore, the synthesis and characterization of reference compounds such as cocaine derivatives can support the development of methods for their identification and quantification. In addition, investigating authorities can gain better insides into the quality of the sold substances and the production methods in clandestine labs. Due to their structural similarities with cocaine and benzoylecgonine, a cross-reactivity in immunochemical assays was presumed but can be excluded for the CEDIA cocaine assay. All aimed synthetic cocaine derivatives were successfully synthesized and characterized. These substances will support the development of analytical methods and support their coverage in the daily forensic routine. The tested cocaine derivatives showed no significant cross-reactivity in the CEDIA cocaine immunoassay. While immunochemical assays are very helpful for the initial identification of drug users by police and forensic-toxicological laboratories, the cross-reactivity should be evaluated in other test systems.

Identification of the novel synthetic cannabinoid-type new psychoactive substance, CH-PIACA, in seized material

Synthetic cannabinoids (SCs) remain the largest class of new psychoactive substances (NPS) according to the European Monitoring Centre for Drugs and Drug Addiction (EMDCDDA) and while the number of new analogues that are reported for the first time each year declines, SCs are reported the most compared to other NPS classes. This decline can be seen as a result of legislative changes by different jurisdictions which have sometimes transitioned to a more generalized approach when controlling substances by defining common structural scaffolds rather than explicit structures. While the consequences of such legislative changes have been expected over the years, the introduction of so called “class-wide” bans has put further pressure on clandestine laboratories to synthesize compounds which are out of the scope of the legislation and thus these compounds are initially harder to detect and/or identify in forensic chemistry or medico-legal contexts in the absence of analytical data. Recently, a synthetic cannabinoid with an indole-3-acetamide core-linker scaffold, AD-18 (i.e. ADB-FUBIATA or ADB-FUBIACA), was reported for the first time in China in 2021. Here, an additional cannabinoid with the indole-3-acetamide scaffold, N-cyclohexyl-2-(1-pentyl-1H-indol-3-yl)acetamide (tentatively CH-PIACA) was structurally characterized using gas chromatography – mass spectrometry (GC-MS), liquid chromatography – high-resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR) spectroscopy. A beige powder in a zip-lock bag was seized by The Danish Customs Agency and subsampled by combining three aliquots of approximately 1 g after homogenization with a mortar and pestle. Sample solutions for GC-MS and UHPLC-QTOF-MS were prepared by dissolving the material in methanol and 25% methanol + 1% formic acid, respectively. For NMR, 3 mg of the powder was dissolved in DMSO-d6 and filtered into an NMR tube. Routine GC-MS analysis of the seized material yielded a single major peak at 22.156 min with a molecular ion at m/z 326.3 and fragment ions at m/z 200, 144 and 130 in the electron ionization mass spectrum (EI-MS). In addition, a major component was observed at 11.91 min in the UHPLC-QTOF-MS screening which had a precursor ion at m/z 327.2450 corresponding to a compound with a molecular formula of C21H30N2O. Similar product ions were observed in the electrospray ionization tandem MS (ESI-MS/MS) spectrum with m/z 245.1644, 200.1441, 144.0808, 130.0651, 100.1120 and 83.0853. NMR spectroscopy with 1H, 13 C, COSY, HMBC and HSQC indicated that the structure was likely to be a substituted indole with a pentyl chain and N-cyclohexylacetamide at the 1- and 3 positions. This structure was corroborated by the EI-MS and ESI-MS/MS data with the neutral loss of N-cyclohexyl-carboxamide (C7H13NO, 127.0997 Da) via cleavage of the bond between the α and β carbons forming m/z 200.1441, while the product ion at m/z 245.1644 corresponded to the loss of cyclohexene from the amide nitrogen. The loss of the N-cyclohexyl-carboxamide was also followed by the loss of the pentyl chain from the nitrogen of the indole ring to yield m/z 130.0651, while m/z 100.1120 corresponded to the cyclohexylammonium cation. The product ion at m/z 144.0808 was proposed to be due to the loss of both the N-cyclohexyl-carboxamide and cleavage of the pentyl chain to liberate 1-butene. A new SC with the indole-3-acetamide scaffold was identified in a seized material in Denmark and characterized using GC-MS, UHPLC-QTOF-MS and NMR spectroscopy. This marks the second SC with this scaffold that has been reported with further analogues anticipated to emerge in the near future.

Forensic profiling of Methamphetamine concealed in chinese teabags seized from multiple drug operations in the Philippines: A case report

Establish the profile of Methamphetamine found inside Chinese teabags in the Philippines. Chinese teabags encountered by the PDEA Laboratory from March 2019 to June 2021 with labels “Guanyingwang”, “Chinese Pin Wei”, “Daguanying”, “Qing Shan” and “Alishan Jin Xuan Tea” were sampled and subjected to analysis. Different packaging varieties were noted for “Guanyinwang” and “Daguanyin” labels. The samples were profiled using GCMS and GCFID. The melting point was determined for each sample. Chiral analysis was done using GCFID. Impurity profiling was conducted using GCMS and GCFID. Adulterants were determined via Raman Spectrometer and GCMS. The chemical profile of the said samples were determined to evaluate possible trends and patterns, using recommended methods for methamphetamine profiling (UNDICP, 2000). The stimulant D-methamphetamine was the dominant chirality type among samples tested. However, L-methamphetamine were also detected. In terms of methamphetamine manufacturing starting material, almost all samples analyzed were produced via Ephedrine/pseudoephedrine route. Adulterants were determined in the samples seized from NCR, IVA and BARMM. These adulterants were alum, isopropylbenzylamine and sodium sulfate. No local clandestine laboratory detected yet for Chinese teabags, which supports the idea that it comes from overseas. Alarmingly, it seems that the majority of the source of methamphetamine in the Philippines is now shifting to the Golden Triangle Drug Syndicate that mainly operates on the borders of Myanmar, Laos and Thailand. The concealment trademark (Chinese teabags) of the Golden Triangle Drug Group, appears to be a diversionary tactic in order for other countries to think that its methamphetamine source comes from China. Chinese teabags labels noted in Malaysia and Thailand were “Qing Shan” and “Daguanying” (UNODC, 2019). The samples from seaport interdiction operation in Region V may imply possible local smuggling routes from Luzon to Mindanao or vice-versa. Importantly, the existing information provides vital intelligence lead among law enforcers and investigators dealing with anti-drug operations, as well as forensic chemists dealing with drug profiling and research works on methamphetamine concealed in Chinese teabags.

Deposition of methamphetamine residues produced by simulated smoking

In New Zealand, many concerns have been raised over the presence of methamphetamine contamination in households, especially when its provenance is unknown. Previous research found that contamination levels on household surfaces were higher after the premises had been used as a clandestine laboratory. It is believed that the levels of contamination produced from smoking methamphetamine are much less than those produced through manufacture. This study’s aim was to determine the amount of methamphetamine contamination produced, after simulated smoking, on a range of common, smooth surface types. Accumulation over time was also investigated. The experiment, comprising four simulated smoking events (referred to as ‘smokes’) of 0.2 g followed by a fifth simulated smoking event of 1.2 g (a cumulative total of 2 g) of methamphetamine hydrochloride, was carried out in a shipping container. Subsequent swabs were taken from squares of 100 cm2, following the NIOSH 9111 method. Results were quantified using LC-MS/MS. The methamphetamine concentrations measured gave a range from an overall mean of 0.91 µg/100 cm2 after the first smoke and 15.9 µg/100 cm2 after the final smoke. A rate of accumulation for each surface type was established, as well as an order of surfaces showing the most to least observed contamination. A significant reduction in the level of contamination was observed over a short period of time, although a clear rate was not established. Finally, a relationship between the recovered amounts of methamphetamine and amphetamine produced through the pyrolysis (smoking) process was also determined.

Identification of the synthetic cannabinoid-type new psychoactive substance, CH-PIACA, in seized material.

Synthetic cannabinoids (SCs) remain the largest class of new psychoactive substances (NPS), and while the number of NPS that are reported to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) for the first time each year declines, the number of newly reported SCs still exceeds other NPS classes. This decline can be seen as a result of legislative changes by different jurisdictions which have sometimes transitioned to a more generalized approach when controlling substances by defining common structural scaffolds rather than explicit structures. While the consequences of such legislative changes have been expected over the years, the introduction of so‐called “class‐wide” bans puts further pressure on clandestine laboratories to synthesize compounds which are out of the scope of the legislation, and thus, these compounds are initially harder to detect and/or identify in the absence of analytical data. Recently, a SC with an indole‐3‐acetamide core‐linker scaffold, AD‐18 (i.e., ADB‐FUBIATA or ADB‐FUBIACA), was reported for the first time in China in 2021. Here, an additional cannabinoid with the indole‐3‐acetamide scaffold, N‐cyclohexyl‐2‐(1‐pentyl‐1H‐indol‐3‐yl)acetamide (CH‐PIACA), is reported which was identified for the first time in a seized material in Denmark. Structural characterization was performed using gas chromatography–mass spectrometry (GC–MS), liquid chromatography‐high‐resolution mass spectrometry (LC‐HRMS), and nuclear magnetic resonance (NMR) spectroscopy.

Detection of the Synthetic Cannabinoids AB-CHMINACA, ADB-CHMINACA, MDMB-CHMICA, and 5F-MDMB-PINACA in Biological Matrices: A Systematic Review.

Simple SummarySynthetic cannabinoids were originally developed for scientific research and potential therapeutic agents. However, clandestine laboratories synthesize them and circumvent legal barriers by falsely marketing them as incense or herbal products. They have serious adverse effects, and new derivatives are continuously found in the market, making their detection difficult due to the lack of comparative standards. Human matrices are used to identify the type of synthetic cannabinoid and the time of its consumption. This review discusses the use of hair, oral fluid, blood, and urine in the detection and quantification of some of the major synthetic cannabinoids. Based on the results, some recommendations can be followed, for example, the use of hair to detect chronic and retrospective consumption (although sensitive to external contamination) and oral fluid or blood for the simultaneous detection of the parent compounds and their metabolites. If longer detection times than blood or oral fluid are needed, urine is the matrix of choice, although its pH may intervene in the analysis. This work highlights the use of new techniques, such as high-resolution mass spectrometry, to avoid the use of previous standards and to monitor new trends in the drug market.New synthetic cannabinoids (SCs) are emerging rapidly and continuously. Biological matrices are key for their precise detection to link toxicity and symptoms to each compound and concentration and ascertain consumption trends. The objective of this study was to determine the best human biological matrices to detect the risk-assessed compounds provided by The European Monitoring Centre for Drugs and Drug Addiction: AB-CHMINACA, ADB-CHMNACA, MDMB-CHMICA, and 5F-MDMB-PINACA. We carried out a systematic review covering 2015 up to the present date, including original articles assessing detection in antemortem human biological matrices with detailed validation information of the technique. In oral fluid and blood, SC parent compounds were found in oral fluid and blood at low concentrations and usually with other substances; thus, the correlation between SCs concentrations and severity of symptoms could rarely be established. When hair is used as the biological matrix, there are difficulties in excluding passive contamination when evaluating chronic consumption. Detection of metabolites in urine is complex because it requires prior identification studies. LC-MS/MS assays were the most widely used approaches for the selective identification of SCs, although the lack of standard references and the need for revalidation with the continuous emergence of new SCs are limiting factors of this technique. A potential solution is high-resolution mass spectrometry screening, which allows for non-targeted detection and retrospective data interrogation.

Forensic Electrochemistry: Electrochemical Analysis of Trace Methamphetamine Residues on Household Surfaces

Illicit methamphetamine is known to be the most manufactured amphetamine-type stimulants worldwide. Relatively simple manufacturing procedure had resulted in the creations of manufacturing sites in a variety of premises and structures, deserving forensic investigation. Therefore, this study was aimed to develop an electrochemical detection technique to determine the residual methamphetamine contamination on various surfaces. Carbon materials, namely graphene oxide, graphene nanoplatelets, graphene ink, and glassy carbon microsphere modified glassy carbon electrode were used in detecting methamphetamine by differential pulse voltammetry (DPV). The surface morphology modified electrode was characterised and its electrochemical behaviour was determined. Under optimal conditions, the calibration curve showed bilinear in the concentration range of 1−40 μM and 40−120 μM with good precision and accuracy. The limit of detection was determined to be 0.3 μM. Graphene oxide modified electrode coupled with DPV successfully detected the residual methamphetamine on four household surfaces, including glass, stainless steel, plastic, and varnished wood with recoveries greater than 82%. To conclude, a novel electrochemical detection technique for the presence of methamphetamine was successfully developed to be applied in clandestine laboratory settings. It would be beneficial to assist the forensic investigation, especially for those forensic evidence recovered from suspicious and suspected clandestine laboratories.

Stability of selected substances related to the clandestine production of amphetamine-type stimulants in wastewater:Identification of transformation products

Environmental impact of toxic and corrosive synthesis waste generated by the clandestine production of amphetamine-type stimulants (ATS) is a known problem, which can even result in malfunction of wastewater treatment plants (WWTPs), e. g. in case of illegal discharge of large amounts of highly acidic chemical waste into the sewage system, which is generated in clandestine labs converting pre-precursors to the most prevalent ATS precursor benzyl methyl ketone (BMK). ATS synthesis-specific substances, precursor chemicals, intermediates and route-specific by-products may also support wastewater-based epidemiology (WBE) studies to explain abnormally high loads of drugs in wastewater by distinguishing whether these high loads were caused by consumption or disposal of synthesis waste into the sewage system. Although some of these synthesis-specific substances can be detected in traces in the final form of consumption of the product, these substances are removed from the drug product to a large extent during cleaning steps, e.g. the frequently applied steam distillation step to purify the amphetamine raw base after clandestine Leuckart synthesis. In contrast, these synthesis-specific by-products are very prominent in chemical synthesis wastes, whereby their detection in wastewater would prove a disposal of synthesis wastes instead of excretion after drug product consumption. As a prerequisite, such substances need to exhibit a certain chemical and biological stability in wastewater and, therefore, lab-scale experiments were performed in a mixture of WWTP effluent and activated sludge. Fourteen selected synthesis-specific substances, all related to the production of ATS, comprised pre-precursors (e.g. α-phenylacetoacetonitrile (APAAN) or α-phenylacetoacetamide (APAA)), precursors (e.g. BMK), intermediates (e.g. N-formylamphetamine (NFA)), synthesis by-products (e.g. N,N-di-(β-phenylisopropyl)amine (DPIA)) and final products (e.g. amphetamine (AMPH)). Stability of test substances was evaluated by targeted HPLC-MS/MS analysis, while HPLC-HRMS techniques were used for the identification of transformation products (TPs) of substances that have undergone primary degradation. All substances were detectable for five days minimum and seven out of 14 substances underwent at least primary degradation. A total of three TPs were identified: TP164 was formed by oxidation of ephedrine (EPHE) and was further transformed after maximum formation, while TP180-1 and TP180-2 were formed by reduction of APAA and both remained stable. This is the first study investigating the stability of ATS synthesis-specific substances in wastewater demonstrating sufficient stability for wastewater monitoring studies.

Contribution of Illicit Drug Use to Pharmaceutical Load in the Environment: A Focus on Sub-Saharan Africa.

Illicit drug abuse and addiction are universal issues requiring international cooperation and interdisciplinary and multisectoral solutions. These addictive substances are utilized for recreational purposes worldwide, including in sub-Saharan Africa. On the other hand, conventional wastewater treatment facilities such as waste stabilization ponds lack the design to remove the most recent classes of pollutants such as illicit drug abuse. As a result, effluents from these treatment schemes contaminate the entire ecosystem. Public health officials are concerned about detecting these pollutants at alarming levels in some countries, with potential undesirable effects on aquatic species and increased health hazards through exposure to contaminated waters or recycling treated or untreated effluents in agriculture. Contaminants including illicit substances enter the environment by human excreta following illegal intake, spills, or through direct dumping, such as from clandestine laboratories, when their manufacturer does not follow accepted production processes. These substances, like other pharmaceuticals, have biological activity and range from pseudopersistent to highly persistent compounds; hence, they persist in the environment while causing harm to the ecosystem. The presence of powerful pharmacological agents such as cocaine, morphine, and amphetamine in water as complex combinations can impair aquatic organisms and human health. These compounds can harm human beings and ecosystem health apart from their low environmental levels. Therefore, this article examines the presence and levels of illicit substances in ecological compartments such as wastewater, surface and ground waters in sub-Saharan Africa, and their latent impact on the ecosystem. The information on the occurrences of illicit drugs and their metabolic products in the sub-Saharan Africa environment and their contribution to pharmaceutical load is missing. In this case, it is important to research further the presence, levels, distribution, and environmental risks of exposure to human beings and the entire ecosystem.

About some features of the inspection of clandestine laboratories for the production, manufacture and processing of narcotic drugs, psychotropic substances and their analogues

About some features of the inspection of clandestine laboratories for the production, manufacture and processing of narcotic drugs, psychotropic substances and their analogues

In Vitro and In Vivo Analysis of Fentanyl and Fentalog Metabolites using Hyphenated Chromatographic Techniques: A Review.

Fentanyl and fentanyl analogues (also called fentalogs) are used as medical prescriptions to treat pain for a long time. Apart from their pharmaceutical applications, they are misused immensely, causing the opioid crisis. Fentanyl and its analogues are produced in clandestine laboratories and sold over dark Web markets to different parts of the world, leading to a rise in the death rate due to drug overdose. This is because the users are unaware of the lethal effects of the newer forms of fentalogs. Unlike other drugs, these fentalogs cannot be detected easily, as very little data are available, and this is one of the major reasons for the risk of life-threatening poisoning or deaths. Hence, rigorous studies of these drugs and their possible metabolites are required. It is also necessary to develop techniques for the detection of minute traces of metabolites in biological fluids. This Review provides an overview of the application of hyphenated chromatographic techniques used to analyze multiple novel fentalogs, using in vivo and in vitro methods. The article focuses on the metabolites formed in phase I and phase II processes in biological specimens obtained in recent cases of drug abuse and overdose deaths that could be useful for the detection and differentiation of multiple fentalogs.

Does the ‘Two Dogs’ Method of Clandestine Synthesis Use Precursors that are not Legally Regulated on the Australian East Coast?

In the State of New South Wales (NSW), Australia, the prosecution in criminal proceedings is seeking deterrence punishment for offenders manufacturing 3,4-methylenedioxyamphetamine (MDA) from the precursor helional via the ‘Two Dogs’ method (TDM). The reason given by the prosecution is a presumption that the TDM does not use any unrestricted chemicals in the synthesis of MDA. A comprehensive literature search was conducted. The relevant law was searched to fact-check the assertion of the prosecution. It was found that the prosecution was incorrect. Intermediate precursors of the TDM are restricted in NSW. However, the starting precursor helional remains unscheduled in NSW, yet helional is scheduled in some other Australian States. The prosecution’s position may play a significant factor in the sentencing proceedings of offenders. Therefore, as a matter of urgency, the prosecution must review and update its position and its submissions, keeping with the factual position in relation to the legal provisions of precursors used in the TDM.

Illicitly Manufactured Fentanyl Entering the United States.

The 'third wave' of the ongoing opioid overdose crisis in the United States (US) is driven in large measure by illicitly manufactured fentanyl (IMF), a highly potent synthetic opioid or an analog developed in clandestine laboratories primarily in China and Mexico. It is smuggled into this country either as IMF or as precursors. The southern border of the US is a frequent point of entry for smuggled IMF and the amounts are increasing year over year. IMF is also sometimes mixed in with other substances to produce counterfeit drugs and dealers as well as end-users may not be aware of IMF in their products. IMF is inexpensive to produce and when mixed with filler materials can be used to cut heroin, vastly expanding profitability. It is an attractive product for smuggling as very tiny amounts can be extremely potent and highly profitable. Drug trafficking over the border also involves the tandem epidemic of money laundering as drugs enter the country and cash payments exit. While drug smuggling in and out of the US (and other nations) has been going on for decades, the patterns are changing. Highly potent and potentially lethal IMF is a dangerous new addition to the illicit drug landscape and one with disastrous consequences.

Establishing likelihood ratios for evaluating opposing propositions concerning the activity causing methamphetamine contamination: Smoking or manufacture?

In New Zealand, concerns have been raised over the presence of methamphetamine contamination in households, especially when the activity causing the contamination is unknown. The cause of contamination is also a contentious issue in clandestine laboratory cases concerning charges in relation to “Use of Premises” (Section 12: Misuse of Drugs Act 1975, New Zealand). Regardless of the cause, other than scientific opinion, there is currently no analytical technique that can satisfactorily address the provenance of methamphetamine residues. For several years, approximate methamphetamine contamination levels have been collected from suspected clandestine laboratories in New Zealand, where methamphetamine is believed to have been manufactured. This study used this data and compared it to similar data from properties where the drug is suspected to have been used (smoked) to model likelihood ratios (LR). It is well documented that the LR forms the backbone to a Bayesian method of interpreting forensic evidence. As such, this data has the potential to underpin a novel Bayesian approach in the evaluation of clandestine laboratory evidence.