A fatal mono-intoxication with 4-fluoroisobutyrylfentanyl: Case report with postmortem concentrations.

We report on a case of a 35-year-old man who died suddenly and unexpectedly due to a 4-fluoroisobutyrylfentanyl (4-FIBF) mono-intoxication. Pathological, toxicological and chemical investigations were conducted at the Netherlands Forensic Institute. A full three-cavity forensic pathological examination was performed according to international guidelines. Biological samples obtained during autopsy were comprehensively investigated for the presence of toxic substances using headspace gas chromatography (GC) with flame ionization detection, liquid chromatography-time-of-flight mass spectrometry (LC-TOF-MS), GC-MS, high-performance LC with diode array detection and LC-tandem MS (LC-MS-MS). The seized crystalline substance found next to the body was investigated using a presumptive color test, GC-MS, Fourier-transform infrared spectroscopy and nuclear magnetic resonance. Pathological investigation identified minor lymphocytic infiltrates in the heart, considered irrelevant for the cause of death. Toxicological analysis of the victims' blood indicated the presence of a fluorobutyrylfentanyl (FBF) isomer, with no other compounds detected. The FBF isomer was identified in the seized crystalline substance as 4-FIBF. 4-FIBF concentrations were quantified in femoral blood (0.030 mg/L), heart blood (0.12 mg/L), vitreous humor (0.067 mg/L), brain tissue (>0.081 mg/kg), liver tissue (0.44 mg/kg) and urine (approximately 0.01 mg/L). Based on the outcomes of the pathological, toxicological and chemical investigations, the cause of death of the deceased was attributed to a fatal 4-FIBF mono-intoxication. The presented case underlines the added value of a combined bioanalytical and chemical investigative approach to identify and subsequently quantify fentanyl isomers in postmortem cases. Furthermore, it demonstrates the importance of investigating the postmortem redistribution of novel fentanyl analogs to establish reference values and to subsequently allow for correct interpretation of cause of death analysis in future casework.

Real-time electrochemical screening of cocaine in lab and field settings with automatic result generation.

This work presents the results of a novel application for the fast on-site screening of cocaine and its main cutting agents in suspicious and confiscated samples. The methodology behind the novel application consists of portable electrochemical detection coupled with a peak recognition algorithm for automated result output generation, validated both in laboratory and field settings. Currently used field tests, predominantly colorimetric tests, are lacking accuracy, often giving false positive or negative results. This presses the need for alternative approaches to field testing. By combining portable electrochemical approaches with peak recognition algorithms, an accuracy of 98.4% concerning the detection of cocaine was achieved on a set of 374 powder samples. In addition, the approach was tested on multiple "smuggled," colored cocaine powders and cocaine mixtures in solid and liquid states, typically in matrices such as charcoal, syrup, and clothing. Despite these attempts to hide cocaine, our approach succeeded in detecting cocaine during on-site screening scenarios. This feature presents an advantage over colorimetric and optical detection techniques, which can fail with colored sample matrices. This enhanced accuracy on smuggled samples will lead to increased efficiency in confiscation procedures in the field, thus significantly reducing societal economic and safety concerns and highlighting the potential for electrochemical approaches in on-the-spot identification of drugs of abuse.

Electrochemical profiling and liquid chromatography-mass spectrometry characterization of synthetic cathinones: From methodology to detection in forensic samples.

The emergence of new psychoactive drugs in the market demands rapid and accurate tools for the on-site classification of illegal and legal compounds with similar structures. Herein, a novel method for the classification of synthetic cathinones (SCs) is presented based on their electrochemical profile. First, the electrochemical profile of five common SC (i.e., mephedrone, ethcathinone, methylone, butylone, and 4-chloro-alpha-pyrrolidinovalerophenone) is collected to build calibration curves using square wave voltammetry on graphite screen-printed electrodes (SPEs). Second, the elucidation of the oxidation pathways, obtained by liquid chromatography-high-resolution mass spectrometry, allows the pairing of the oxidation products to the SC electrochemical profile, providing a selective and robust classification. Additionally, the effect of common adulterants and illicit drugs on the electrochemical profile of the SC is explored. Interestingly, a cathodic pretreatment of the SPE allows the selective detection of each SC in presence of electroactive adulterants. Finally, the electrochemical approach is validated with gas chromatography-mass spectrometry by analyzing 26 confiscated samples from seizures and illegal webshops. Overall, the electrochemical method exhibits a successful classification of SC including structural derivatives, a crucial attribute in an ever-diversifying drug market.

Adverse effects of levamisole in cocaine users: a review and risk assessment.

The immunomodulatory adjuvant and antihelminth levamisole is increasingly used as an adulterant in cocaine worldwide. An accumulating body of clinical and toxicological literature has appeared since 2010 describing neutropenia, agranulocytosis, leukoencephalopathy and vasculitis in cases associated with levamisole-adulterated cocaine. Mostly, neutropenia and agranulocytosis were reported, characterized by a decimation of neutrophils. A large proportion of cases also involved vasculopathy, characterized by pronounced black and purple skin purpura with cutaneous necrosis. Females are more susceptible for both agranulocytosis and vasculitis. Another complication reported with levamisole-adulterated cocaine is leukoencephalopathy, a disabling and potentially fatal neurological disorder caused by cerebral demyelination. In this review, all adverse effects associated with therapeutic levamisole and levamisole-adulterated cocaine are described. In addition, this review provides an update of the pharmacology of levamisole, its metabolism, including toxic metabolites and metabolites that are relevant for levamisole's addition to cocaine. Special emphasis is put on the immunopathology and the dose-effect relationship of chronic levamisole exposure. Finally, a risk assessment is provided based on the current level of levamisole adulteration in street cocaine, the dose range calculated per gram and the pattern of chronic exposure in heavy or dependent users.

The interface between forensic science and technology: how technology could cause a paradigm shift in the role of forensic institutes in the criminal justice system.

In this paper, the importance of modern technology in forensic investigations is discussed. Recent technological developments are creating new possibilities to perform robust scientific measurements and studies outside the controlled laboratory environment. The benefits of real-time, on-site forensic investigations are manifold and such technology has the potential to strongly increase the speed and efficacy of the criminal justice system. However, such benefits are only realized when quality can be guaranteed at all times and findings can be used as forensic evidence in court. At the Netherlands Forensic Institute, innovation efforts are currently undertaken to develop integrated forensic platform solutions that allow for the forensic investigation of human biological traces, the chemical identification of illicit drugs and the study of large amounts of digital evidence. These platforms enable field investigations, yield robust and validated evidence and allow for forensic intelligence and targeted use of expert capacity at the forensic institutes. This technological revolution in forensic science could ultimately lead to a paradigm shift in which a new role of the forensic expert emerges as developer and custodian of integrated forensic platforms.

Different likelihood ratio approaches to evaluate the strength of evidence of MDMA tablet comparisons.

Two likelihood ratio (LR) approaches are presented to evaluate the strength of evidence of MDMA tablet comparisons. The first one is based on a more 'traditional' comparison of MDMA tablets by using distance measures (e.g., Pearson correlation distance or a Euclidean distance). In this approach, LRs are calculated using the distribution of distances between tablets of the same-batch and that of different-batches. The second approach is based on methods used in some other fields of forensic comparison. Here LRs are calculated based on the distribution of values of MDMA tablet characteristics within a specific batch and from all batches. The data used in this paper must be seen as examples to illustrate both methods. In future research the methods can be applied to other and more complex data. In this paper, the methods and their results are discussed, considering their performance in evidence evaluation and several practical aspects. With respect to evidence in favor of the correct hypothesis, the second method proved to be better than the first one. It is shown that the LRs in same-batch comparisons are generally higher compared to the first method and the LRs in different-batch comparisons are generally lower. On the other hand, for operational purposes (where quick information is needed), the first method may be preferred, because it is less time consuming. With this method a model has to be estimated only once in a while, which means that only a few measurements have to be done, while with the second method more measurements are needed because each time a new model has to be estimated.

Effects of traditional processing methods of linseed oil on the composition of its triacylglycerols.

Different oil processing methods were performed, which included washing with water and treatment with lead-based driers, with and without heating to different temperatures, giving a set of 7 oils to be investigated. The effects of the traditional processing methods of linseed oil on its triacylglycerol (TAG) composition were studied, using the following analytical methods: high performance size exclusion chromatography (HPSEC), Fourier transform infrared spectroscopy (FTIR), high-performance liquid chromatography-atmospheric pressure chemical ionisation-mass spectrometry (HPLC-APCI-MS), direct temperature resolved mass spectrometry (DTMS), matrix assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF-MS), and electrospray ionisation Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS). A decrease of the initial cis-double bonds and the formation of trans-double bonds upon heating of the oils was observed. Heating a lead and oil mixture to 150 degrees C, or heating the oil alone to 300 degrees C led to the highest degree of oxidation. A difference was observed for the oxidation patterns for oils with and without the addition of lead. Furthermore, levels of oxygen incorporation were higher when lead was added to the oil. High temperature treatment of the oils resulted in an increased average molecular weight. The changes in the initial conformation of the double bond systems observed with FTIR were supported by HPLC-APCI-MS measurements that showed the formation of a number of new isomeric TAGs in the heated oil compared to freshly pressed, untreated oil. Oligomerisation up to hexamers was observed with HPSEC, and MALDI-TOF-MS. The formation of oligomers up to trimers only, however, was observed with ESI-FTICR-MS. Incorporation of oxygen was mainly observed with MALDI-TOF-MS and ESI-FTICR-MS whereas with DTMS and FTIR hardly any evidence was found for this.

Identification of non-cross-linked compounds in methanolic extracts of cured and aged linseed oil-based paint films using gas chromatography-mass spectrometry.

Methanolic extracts of paint samples of different composition and age were qualitatively investigated by GC-MS using an on-column injector after off-line methylation or trimethylsilyl derivatisation, and on-line thermally assisted (trans)methylation with tetramethylammonium hydroxide using Curie-point pyrolysis-GC-MS. The combination of these three analytical strategies led to the identification of typical oxidation products of unsaturated fatty acids by interpretation of their mass spectrum. Some of the identified compounds have not been reported before. Both the off-line and on-line GC-MS strategy show series of short-chain fatty (di)acids and C16 and (oxidised) C18 fatty acids. The major advantage of the on-line pyrolysis-GC-MS approach is that chemical work-up is minimal and very quick. With this technique both the carboxylic acid functionalities, and hydroxyl groups are methylated. Young paint films are shown to contain relatively more oxidised C18 fatty acids and less diacids compared to older paints, which is indicative for the on-going oxidation processes within the paint. After trimethylsilylation, monoacylglycerols are detected indicative for hydrolytic processes, which reflect the relative distribution of the most prominent silylated fatty acids present. Relatively more C16 and C18 monoacylglycerols are found in young paints, whereas older paints contain higher amounts of monoacylglycerols of diacids.