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.     

Fatal intoxication involving 2-methyl AP-237

Novel synthetic opioids contribute considerably to the opioid epidemic, especially with the frequent emergence of structurally similar compounds. This case report describes a fatal intoxication involving 2-methyl AP-237. A 54-year-old Caucasian male was found deceased from an apparent drug overdose. A plastic container labeled “2MAP” and a cut straw were found in the decedent's backpack at the scene. A white substance found in the container tested positive for fentanyl by field testing. According to his medical history, the decedent was treated for a drug overdose 3 years prior to his death. With no diagnostic findings at autopsy, the case was submitted for toxicological analysis. An unknown substance was detected in peripheral blood and urine using gas chromatography with nitrogen phosphorous detection (GC-NPD). Further testing was conducted using gas chromatography–mass spectrometry (GC–MS) and liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS) which confirmed the presence of 2-methyl AP-237 and potential metabolites in blood and urine. Quantitation by GC-NPD revealed concentrations of 2-methyl AP-237 in blood and urine at 480 ng/mL and 4200 ng/mL, respectively. The toxicological analysis also identified and quantitated alprazolam in the blood at 55 ng/mL. Additionally, the metabolism of 2-methyl AP-237 was investigated and three hydroxylated metabolites were identified in peripheral blood and urine. Limited literature is available for the detection and quantitation of 2-methyl AP-237 in postmortem specimens. Given the toxicological findings with unremarkable autopsy findings, this case is an example of a fatal intoxication involving 2-methyl AP-237.     

A reference database of Windows artifacts for file-wiping tool execution analysis

Anti-forensic technology can play an effective role in protecting information, but it can make forensic investigations difficult. Specifically, file-wiping permanently erases evidence, making it challenging for investigators to determine whether a file ever existed and prolonging the investigation process. To address this issue, forensic researchers have studied anti-forensic techniques that detect file-wiping activities. Many previous studies have focused on the effects of file-wiping tools on $MFT, $LogFile, and $DATA, rather than on Windows artifacts. Additionally, previous studies that have examined Windows artifacts have considered different artifacts, making it difficult to study them in a comprehensive manner. To address this, we focused on analyzing traces in 13 Windows artifacts of 10 file-wiping tools' operations in the Windows operating system comprehensively. For our experiments, we installed each file-wiping tool on separate virtual machines and checked the traces that the tools left behind in each artifact. We then organized the results in a database format. Our analysis revealed that most of the tools left traces on other artifacts, except for JumpList, Open&SavePidlMRU, and lnk. There were also some cases where traces remained on the other three artifacts. Based on our research, forensic investigators can quickly identify whether a file-wiping tool has been used, and it can assist in decision-making for evidence collection and forensic triage.     

Pulp volume quantification methods in cone-beam computed tomography for age estimation: A critical review and meta-analysis

The secondary dentin deposition that occurs after the tooth formation process results in a decrease in pulp cavity volume in adolescents and adults. The purpose of this critical review was to correlate pulpal and/or dental volume on cone-beam computed tomography (CBCT) with chronological age approximation. A subobjective was to investigate which methodology and CBCT technical parameters would be most appropriate to evaluate this correlation. This critical review followed the PRISMA guidelines, and it was conducted by a search through PubMed, Embase, SciELO, Scopus, Web of Science, Cochrane Library databases, as well as gray literature. Primary studies that used pulp volume, or pulp chamber to tooth volume ratio measured using CBCT were included. Seven hundred and eight indexed and 31 non-indexed records were identified. A qualitative analysis was performed including 25 selected studies with a total of 5100 individuals, age ranging from 8 to 87 years without sex predilection. The most used method was pulp volume/tooth volume. CBCT voxel size ranged between 0.09 and 0.5. Manual segmentation associated with threshold algorithms was used in most of the studies. Correlation between the pulp volume/tooth volume ratio was moderate: −0.66 for the upper central incisors, −0.59 for upper canines and −0.56 for lower canines. High heterogeneity was observed among the studies. It is concluded that pulp volume should be used with caution in age estimation. Evidence supports the preferable use of upper incisors with pulp volume/tooth volume ratio for age estimation. There is not enough evidence that voxel size interferes in age estimation by pulp volume.     

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.     

Overview of the seized and examined pharmaceutical in the state of Minas Gerais-Brazil by the Civil Police from 2017 to 2022: A fundamental analysis of the recent impact over the drugs market

This work presents a data survey regarding the qualitative chemical analysis of drugs seized by the Police in the state of Minas Gerais between July 2017 and June 2022, including an evaluation of labeling of 265 samples of anabolic androgenic steroids (AAS) seized in 2020. The Active Pharmaceutical Ingredients (API) present in the samples were identified through chemical analysis and classified by system Anatomical Therapeutic Chemical (ATC) methods. Analysis of the labeling information for 265 samples of AAS followed the guidance of legislation RDC 71 (2009) from ANVISA. For this study 6355 seized pharmaceuticals underwent qualitative chemical analysis that corresponded to 7739 APIs successfully identified and classified. Among the components studied AAS, psychostimulants, anesthetics, and analgesics were the most commonly examined. AAS seized and tested increased by over 100% and for the majority of the samples analyzed were found to not match the labeling on the packaging. In the meantime, anti-obesity drugs presented a prominent increase of 400% from 2020/1 to 2021/2, during covid-19 quarantine. Seized pharmaceuticals and tests can support information in the planning of public health and safety policies.     

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.     

Decomposing Audience Costs: Bringing the Audience Back into Audience Cost Theory

According to a growing tradition in International Relations, one way governments can credibly signal their intentions in foreign policy crises is by creating domestic audience costs: leaders can tie their hands by publicly threatening to use force since domestic publics punish leaders who say one thing and do another. We argue here that there are actually two logics of audience costs: audiences can punish leaders both for being inconsistent (the traditional audience cost), and for threatening to use force in the first place (a belligerence cost). We employ an experiment that disentangles these two rationales, and turn to a series of dispositional characteristics from political psychology to bring the audience into audience cost theory. Our results suggest that traditional audience cost experiments may overestimate how much people care about inconsistency, and that the logic of audience costs (and the implications for crisis bargaining) varies considerably with the leader's constituency.     

Fuel to the Fire: Natural Disasters and the Duration of Civil Conflict

Do natural disasters prolong civil conflict? Or are disasters more likely to encourage peace as hostilities diminish when confronting shared hardship or as shifts in the balance of power between insurgents and the state hasten cessation? To address these questions, this study performs an event history analysis of disasters’ impact on the duration of 224 armed intrastate conflicts occurring in 86 states between 1946 and 2005. I contend that natural disasters increase conflict duration by decreasing the state’s capacity to suppress insurgency, while reinforcing insurgent groups’ ability to evade capture and avoid defeat. First, disasters’ economic impact coupled with state financial outlays for disaster relief and reconstruction, reduce resources available for counterinsurgency and nation building in conflict zones. Second, the military’s role in administering humanitarian assistance can reduce the availability of troops and military hardware for counterinsurgency, prompt temporary ceasefires with insurgents, or both. Third, natural disasters can cause infrastructural damages that disproportionately hinder the state’s capacity to execute counterinsurgency missions, thereby making insurgent forces more difficult to capture and overcome. The combination of these dynamics should encourage longer conflicts in states with higher incidence of disaster. Empirical evidence strongly supports this contention, indicating that states with greater disaster vulnerability fight longer wars.     

An Exploratory Study of Honor Crimes in the United States

There is a lack of research on honor crimes within the United States. We used an open source search methodology to identify the victim-offender relationship and motivations for this crime within the United States. Using data collected based on the protocol for the United States Extremist Crime Database (ECDB), we identified a total of 16 honor crimes with 40 victims that occurred between January 1st 1990 and December 31st 2014 in the United States. Based on our findings, the overarching motivations for honor crimes in the United States were the perpetrator’s former partner beginning the process of separation and the westernized behavior of the victim, typically the offender’s daughter or step-daughter. Honor crimes were not limited to current/former intimate partners or daughters, as they also included the death of extended family members (e.g. in-laws, nieces, and cousins). Policy implications and directions for future research on honor crimes are discussed.