Stereochemical Analysis of Methorphan Using (−)‐Menthyl Chloroformate

Abstract: Forensic laboratories around the world have seen an increase in the number of drug seizures containing methorphan. Levomethorphan is a narcotic and a controlled substance, and its enantiomer dextromethorphan is an antitussive agent used in over‐the‐counter medications. For the forensic analysis of seized drugs containing methorphan, it is important to report the stereochemical composition of the drug. Ideally, a method based on common forensic laboratory instrumentation is desirable. The use of the chiral derivatizing agent (?)‐menthyl chloroformate followed by routine gas chromatography–mass spectrometry analysis of the derivative was shown to successfully determine the stereochemical composition of methorphan. This approach was applied to a street seizure containing methorphan proving that it was pure dextromethorphan. The derivatives of dextro‐ and levomethorphan were subjected to mass spectroscopic and nuclear magnetic resonance analysis, which confirmed that the structure of the derivatives remained unchanged as a result of the derivatization process.     

Evidence of mephedrone chronic abuse through hair analysis using GC/MS

Mephedrone is a synthetic derivative of cathinone which is becoming more common on the recreational drug market. Several intoxications following mephedrone abuse have been reported though published papers have focused essentially on analytical approaches for biological fluids and only one has involved a hair sample. After the development and validation of a new method, the first series of positive results for mephedrone in hair specimens is reported here. After decontamination of the hair strand in methylene chloride, hair segments were cut into small pieces with scissors, weighed and incubated overnight in Soerensen buffer pH 7.0 in the presence of deuterated 3,4-methylenedioxymethamphetamine (MDMA) at 40°C. The incubation medium was extracted using ethyl acetate after alkalinisation with 1N sodium hydroxide (NaOH). Before injection, the dry extract was derivatized using a mixture of heptafluorobutyric anhydride/ethyl acetate (100:50, v/v), evaporated and dissolved in ethyl acetate (25μl). After introduction of 1μl of the extract onto a splitless injector, chromatographic separation was achieved on a HP 6890 gas chromatograph equipped with a 5-MS capillary column. Detection was achieved in single ion monitoring mode (m/z 254-119-210 for mephedrone, m/z 258-213 for MDMA-d5) using a 5973 MSD operating in electron impact mode. Sixty-seven hair specimens were tested for mephedrone. Thirteen of them were found positive for mephedrone with concentrations ranging from 0.2 to 313.2ng/mg with a mean concentration of 26.8ng/mg. It was difficult to compare our findings due to a lack of reference data, nevertheless mephedrone seems well incorporated into hair (concentrations in the ng/mg range) like other stimulant drugs such as amphetamines or cocaine. The aim of this work was to develop a specific and accurate method for mephedrone analysis in hair specimens and its application to a large number of samples (n=67). The developed analytical method appears sensitive enough to reveal occasional to regular use of mephedrone.     

Influence of CYP2D6 genotype on the disposition of the enantiomers of venlafaxine and its major metabolites in postmortem femoral blood

Venlafaxine (VEN) is an antidepressant drug mainly metabolized by the cytochrome P450 (CYP) enzyme CYP2D6 to the active metabolite O-desmethylvenlafaxine (ODV). VEN is also metabolized to N-desmetylvenlafaxine (NDV) via CYP3A4. ODV and NDV are further metabolized to N,O-didesmethylvenlafaxine (DDV). VEN is a racemic mixture of the S- and R-enantiomers and these have in vitro displayed different degrees of serotonin and noradrenaline reuptake inhibition. The aim of the study was to investigate if an enantioselective analysis of VEN and its metabolites, in combination with genotyping for CYP2D6, could assist in the interpretation of forensic toxicological results in cases with different causes of deaths. Concentrations of the enantiomers of VEN and metabolites were determined in femoral blood obtained from 56 autopsy cases with different causes of death. The drug analysis was done by liquid chromatography tandem mass spectrometry (LC/MS/MS) and the CYP2D6 genotyping by PCR and pyrosequencing. The mean (median) enantiomeric S/R ratios of VEN, ODV, NDV and DDV were 0.99 (0.91), 2.17 (0.93), 0.92 (0.86) and 1.08 (1.03), respectively. However, a substantial variation in the relationship between the S- and R-enantiomers of VEN and metabolites was evident (S/R ratios ranging from 0.23 to 17.6). In six cases, a low S/R VEN ratio (mean 0.5) was associated with a high S/R ODV ratio (mean 11.9). Genotyping showed that these individuals carried two inactive CYP2D6 genes indicating a poor metabolizer phenotype. From these data we conclude that enantioselective analysis of VEN and ODV can predict if a person is a poor metabolizer genotype/phenotype for CYP2D6. Knowledge of the relationship between the S- and R-enantiomers of this antidepressant drug and its active metabolite is also important since the enantiomers display different pharmacodynamic profiles.     

Correlates of Substantiated Emotional Maltreatment in the Second Canadian Incidence Study

The objective of this study was to determine the correlates of substantiated psychological maltreatment (PMT) in Canada on functions of maltreatment characteristics, child profile, household profile, and child protection services interventions. This study is based on a secondary analysis of data collected in the second Canadian Incidence Study. PMT investigations were categorized into six groups: emotional abuse, emotional neglect, and other maltreatment as single form, and these same three groups when they co-occurred with another form of maltreatment. Six logistic regressions, comparing all pairs of groups, were carried out. Cases of PMT (single form) were more chronic and associated with greater adverse emotional impact than other forms of maltreatment. Mothers of psychologically maltreated children had more mental health issues. Emotional neglect cases were more complex (e.g., substance abuse, mental health, and social housing). The three co-occurrent groups present more negative factors but more risk factors are observed when PMT are also observed (e.g., emotional harm, alcohol abuse, housing problems, chronicity, and referral to other services).     

Putting security governance to the test: conceptual,empirical, and normative challenges

Security governance has featured prominently in recent debates about fragmentation, informalization, and privatization in the increasingly diverse field of security policy. It has inspired much valuable research. Yet, there are not just very different conceptual understandings of security governance; there is also a lack of clarity regarding its empirical manifestations and normative connotations. After a decade of research, the special issue therefore puts security governance to the test and scrutinizes its analytical and political pitfalls and potentials. This editorial briefly reviews the rise of security governance, identifies central conceptual, empirical, and normative challenges that need to be addressed, and introduces the individual contributions to this special issue.     

Towards security governance as a critical tool: a conceptual outline

This article argues that security governance can and should be reframed as a critical tool that enables us to understand and reappraise concrete practices of security provision. Security governance needs to move beyond the functional mapping of different governing arrangements and the presumption that security governance leads to effective and legitimate problem-solving in a quasi-automatic manner. In this article, we propose a framework that identifies the essential characteristics of security governance and turns them into critical questions with the aim to reveal persisting frictions and dilemmas. First, we trace the rise of security governance as concept and practice over the past decade and identify its central characteristics with regard to prerequisites, structures and consequences. Second, we reframe the core characteristics of security governance into critical questions and thereby develop an understanding of security governance as a critical tool. Finally, we illustrate the relevance of this approach with examples from EU security governance.     

Equity and cost-effectiveness of multilateral adaptation finance: are they friends or foes?

This paper analyzes potential criteria to allocate international funding for adaptation to climate change, as a response to one of the main governance challenges of international adaptation funding—the prioritization of project proposals given scarce funding. Based on the review of the equity and cost-effectiveness literature and relevant policy documents, we identify three potential indicators for equity (vulnerability level, poverty, equal funding per capita), and three indicators for cost-effectiveness (economic savings in absolute and relative terms, human lives saved). Applying these simple indicators to information provided in all 39 project documents considered by the Adaptation Fund Board (AFB) in 2011, we find that projects approved or endorsed by the AFB rank high according to one cost-effectiveness indicator (absolute economic savings), while they rather rank low according to all equity and further cost-effectiveness indicators. Furthermore, we analyze whether equity and cost-effectiveness are two contradicting goals, or whether ways can be found to reconcile both goals in multilateral adaptation finance. We conclude from both the theory and the 39 analyzed project documents that a pure economic definition of cost-effectiveness tends to be in contradiction with equity but that trade-offs between equity and cost-effectiveness can be limited if relative economic savings or human live savings are used as indicator for cost-effectiveness.     

Evaluation of a Headspace Solid‐Phase Microextraction Method for the Analysis of Ignitable Liquids in Fire Debris

The chemical analysis of fire debris represents a crucial part in fire investigations to determine the cause of a fire. A headspace solid‐phase microextraction (HS‐SPME) procedure for the detection of ignitable liquids in fire debris using a fiber coated with a mixture of three different sorbent materials (Divinylbenzene/Carboxen/Polydimethylsiloxane, DVB/CAR/PDMS) is described. Gasoline and diesel fuel were spiked upon a preburnt matrix (wood charcoal), extracted and concentrated with HS‐SPME and then analyzed with gas chromatography/mass spectrometry (GC/MS). The experimental conditions—extraction temperature, incubation and exposure time—were optimized. To assess the applicability of the method, fire debris samples were prepared in the smoke density chamber (SDC) and a controlled‐atmosphere cone calorimeter. The developed methods were successfully applied to burnt particleboard and carpet samples. The results demonstrate that the procedure that has been developed here is suitable for detecting these ignitable liquids in highly burnt debris.