Organic impurity profiling of fentanyl samples associated with recent clandestine laboratory methods

Nearly a decade ago, fentanyl reappeared in the United States illicit drug market. In the years since, overdose deaths have continued to rise as well as the amount of fentanyl seized by law enforcement agencies. Research surrounding fentanyl production has been beneficial to regulatory actions and understanding illicit fentanyl production. In 2017, the Drug Enforcement Administration (DEA) began collecting seized fentanyl samples from throughout the United States to track purity, adulteration trends, and synthetic impurity profiles for intelligence purposes. The appearance of a specific organic impurity, phenethyl-4-anilino-N-phenethylpiperidine (phenethyl-4-ANPP) indicates a shift in fentanyl production from the traditional Siegfried and Janssen routes to the Gupta-patent route. Through a collaboration between the DEA and the US Army's Combat Capabilities Development Command Chemical Biological Center (DEVCOM CBC), the synthesis of fentanyl was investigated via six synthetic routes, and the impurity profiles were compared to those of seized samples. The synthetic impurity phenethyl-4-ANPP was reliably observed in the Gupta-patent route published in 2013, and its structure was confirmed through isolation and structure elucidation. Organic impurity profiling results for illicit fentanyl samples seized in late 2021 have indicated yet another change in processing with the appearance of the impurity ethyl-4-anilino-N-phenethylpiperidine (ethyl-4-ANPP). Through altering reagents traditionally used in the Gupta-patent route, the formation of this impurity was determined to occur through a modification of the route as originally described in the Gupta patent.     

Characterization of an odor permeable membrane device for the storage of explosives and use as canine training aids

The storage and use of explosives is regulated at the state and federal level, with a particular focus on physical security and rigorous accounting of the explosive inventory. For those working with explosives for the training and testing of explosive-detecting canines, cross-contamination is an important concern. Hence, explosives intended for use with canine teams must be placed into secondary storage containers that are new, clean, and airtight. A variety of containers meet these requirements and include screw-top glass jars (e.g., mason jars). However, an additional need from the explosive-detecting canine community is secondary containers that can also be used as training aids whereby the volatiles emitted by explosives are emitted in a predictable and stable manner. Currently, a generally accepted method for the storage of explosives and controlled emission of explosive vapor for canine detection does not exist. Ideally, such containers should allow odor to escape from the training aid but block external contaminates such as particulates or other volatiles. One method in use places the explosive inside a permeable cotton bag when in use for training and then stores the cotton bag inside an impermeable nylon bag for long-term storage. This paper describes the testing of an odor permeable membrane device (OPMD) as a new way to store and deploy training aids. We measured the evaporation rate and flux of various liquid explosives and volatile compounds that have been identified in the headspace of actual explosives. OPMDs were used in addition to traditional storage containers to monitor the contamination and degradation of 14 explosives used as canine training aids. Explosives were stored individually using traditional storage bags or inside an OPMD at two locations, one of which actively used the training aids. Samples from each storage type at both locations were collected at 0, 3, 6, and 9 months and analyzed using Fourier Transform Infrared (FTIR) Spectroscopy and Gas Chromatography–Mass Spectrometry (GC–MS) with Solid-Phase Microextraction (SPME). FTIR analyses showed no signs of degradation. GC–MS identified cross-contamination from ethylene glycol dinitrate (EGDN) and/or 2,3-dimethyl-2,3-dinitrobutane (DMNB) across almost all samples regardless of storage condition. The contamination was found to be higher among training aids that were stored in traditional ways and that were in active use by canine teams.     

Evaluating the discriminating power of amino acid ratios on distinguishing dark colored hair samples

Human hairs are one of the most commonly encountered items of trace evidence. Currently, conventional methods for hair analysis include microscopic comparison and DNA analysis (nuclear and mitochondrial). Each approach has its own drawbacks. Hair proteins are stable and offer an alternative to DNA testing, as demonstrated with proteomics for distinguishing humans. However, proteomics is complicated and requires identifying peptides to remain intact following harsh sample preparation methods. Alternatively, the actual amino acid content of a hair sample may also offer important identifying information and actually requires proteins and peptides to be broken down completely rather than remaining intact. This study evaluated the discriminating power of using hair amino acid ratios to differentiate hair samples from 10 unrelated individuals with dark colored hair. Hair proteins were digested, derivatized, and analyzed using gas chromatography–mass spectrometry. Amino acid ratios were calculated for each individual and comparisons using ANOVA and post-hoc pairwise t-test with Bonferroni correction were made with amino acid ratios for individuals. Overall, out of the 45 possible pairwise comparisons between all hair samples, 38 (84%) were differentiable. Out of the 36 possible pairwise comparisons between brown haired individuals, 32 (89%) were considered differentiable using univariate statistics. Multivariate statistics were also attempted but, overall, univariate models were sufficient for exclusionary purposes. These results indicate that amino acid ratio analysis can potentially be used as an exclusionary method using hair if DNA analysis cannot be performed, or to corroborate conclusions made following microscopic analysis.     

The March Towards Post‐Democracy,Ten Years On

Events since I published my book Post‐democracy in 2004 suggest that democracy continues to decline in effectiveness in those parts of the world where it has been most strongly established. The global financial crisis, the consequent euro crisis, the likely shape of a Transatlantic Trade and Investment Partnership (TTIP) and growing evidence of the political power of giant mass media corporations all suggest that the dominant forces in today's politics are not those of democratic will. Movements like Syriza in Greece possibly suggest a democratic reawakening, but that is too early to determine. Meanwhile, it is important also to be aware of democracy's limits, and to try to resolve the problem of post‐democracy by extending its reach beyond its competence.     

Untangling Housing Cost and Transportation Interactions: The Location Affordability Index Model—Version 2 (LAIM2)

Abstract

It is now accepted that to have an understanding of housing affordability one must consider not only housing costs, but also the transportation costs associated with that household location. To make this information readily accessible to the public, the United States government created an Internet resource, the Location Affordability Portal – Version 2 (www.locationaffordability.info), to provide housing and transportation costs for every neighborhood in all 50 states and the District of Columbia. Although the statistical model at the heart of this resource was designed for predictive accuracy, its design and parameter estimates can provide additional insights into the interaction of housing cost and transportation choices (and thus its cost). This study describes the development and explores the policy implications (and limitations) of this structural equations model, the Location Affordability Index Model – Version 2 (LAIM2).     

The Responsibility to Protect at Ten: Glass Half Empty or Half Full?

Abstract

Far from having faded away, ten years after its formal adoption, the responsibility to protect (R2P), is arguably more relevant than ever. In the current overall context of protection crises, heightened in severity by the emergence of violent extremists, R2P has changed the way in which the international community characterises situations that involve protection failures, and has raised expectations about what should occur when atrocity crimes have been committed or are imminent. UN member states now agree that prevention is at the core of R2P, that international action should employ the full range of diplomatic, political and humanitarian measures, and that military force should only be considered as a measure of last resort. While there is continued contestation about particular aspects of R2P – as there is over much older normative advancements, such as human rights – R2P has helped to forge political consensus and build new institutional capacity to prevent and respond to atrocity crimes.     

Position Effect on Facial Soft Tissue Depths: A Sonographic Investigation

The head is positioned erect for an approximation; yet most facial soft tissue depths (FSTD) used are measured from supine subjects. Depth difference might be significant, but there is a paucity of data to verify. This study compared erect and supine values for 17 landmarks from 30 healthy New Zealand (European population affinity) women (18–30 or 40–55 years) in erect then supine positions. Height, weight, and sonographic FSTD data, totaling 1020 measurements, were obtained. Three midline and seven averaged bilateral values were compared using ANOVA, p values, and Pearson's correlations. Correlative strength of age and body mass index, BMI (kg/m²), was determined by values. Results showed averaged erect and supine differences were significant for four of ten FSTDs. Between individuals, difference was various and not unidirectional. In conclusion, depth differences were observed but not all significant or unidirectional, BMI significantly influenced nine FSTD values, but age group did not.     

Fatal Intoxication with Toluene Due to Inhalation of Glue

Two cases of fatal intoxications with toluene due to glue sniffing are described. In case 1, the autopsy did not indicate cause of death, while in case 2, the cause of death was determined to possibly be due to mechanical asphyxia by drowning. As the decedents had a history of glue sniffing, toxicological analyses were performed. Using gas chromatography with flame ionization detector and gas chromatography/mass spectrometry (GC/MS) with headspace method, toluene was detected in biological samples. Toluene ranged from 3.81 to 20.97 μg/g, with the highest concentrations observed in liver and brain (13.82–20.97 μg/g) in both cases. Based upon this data, the cause of death in both cases was determined to be toluene poisoning. Toxicological investigations are extremely important and should be considered mandatory in all deaths thought to be due to volatile substance abuse, as well as all deaths that are thought to be due to poisoning in young people.     

Monitoring of Levamisole Concentration in Serum of Traffic Participants after Cocaine Consumption

This study highlights the problem of levamisole‐adulterated cocaine in context of active traffic participation. For the purposes of levamisole concentration monitoring in human serum, an analytical method based on LC‐MS/MS and solid‐phase extraction was applied. A Luna 5 μm C18 (2) 100 A, 150 mm × 2 mm column and a mobile phase consisting of A (H₂O/methanol = 95/5, v/v) and B (H₂O/methanol = 3/97, v/v), both with 10 mM ammonium acetate and with 0.1% acetic acid (pH = 3.2), were used. The validation experiments demonstrated that the method applied was appropriate for levamisole quantification in human serum. For 23% of levamisole‐positive samples, the concentrations exceeded 20 ng/mL. Therefore, the interaction of this drug with cocaine has to be considered as important for active traffic participation. As a consequence, monitoring of levamisole concentration in human serum is recommended, as long as it is used as cocaine adulterant.     

Are America’s public mass shooters unique? A comparative analysis of offenders in the United States and other countries

Public mass shooters are often assumed to be an exceptionally American problem, but little is known about what proportion of global offenders attack in the United States, or how America’s offenders compare to those in other countries. The present study offers the first quantitative analysis of all known offenders from 1966 to 2012 who attacked anywhere on the globe and killed a minimum of four victims. The results suggest that public mass shooters in the United States are significantly more likely to arm themselves with multiple weapons and attack at school and workplace settings, while offenders from other countries are more likely to strike at military sites. These differences may be partially attributable to America’s national gun culture and its particular set of social strains.