From alcohol to liquid ecstasy (GHB)--a survey of old and modern knockout agents. Part 1: historic and classic knockout agents

Alcohol has been the most important knockout drug in history and literature and continues to play an essential role up to now. Blunt force to the head in the form of a knockout punch is another mechanism leading to a transient loss of consciousness. Diethyl ether and chloroform are among the classical knockout substances. Although they have meanwhile been replaced by modern sedatives and hypnotics, their use is still observed in isolated cases.     

From alcohol to liquid ecstasy (GHB)--a survey of old and modern knockout agents. Part 2: benzodiazepines and other sedatives/hypnotic drugs

Owing to the rapid progress in the development of synthetic pharmaceuticals, the classical knockout drugs such as chloroform and diethyl ether have been superseded by highly effective sedative and hypnotic drugs (e. g. methyprylone, clozapine and especially benzodiazepines). These are frequently given to the victim unnoticed by adding them to an alcoholic drink. In this way, alcohol still plays an important role as an interaction partner. The article presents relevant case examples together with their criminalistic background.     

The reactivity of gamma-hydroxybutyric acid (GHB) and gamma-butyrolactone (GBL) in alcoholic solutions

In this work the stability of GBL (gamma-butyrolactone) and GHB (gamma-hydroxybutyric acid) in alcoholic media was studied. Under acidic conditions the GBL will react with ethanol or methanol to give the corresponding ethyl and methyl esters of GHB. It can be seen that ester formation is dependent on the type of alcohol, the alcohol content of the solution, and the pH of the solution. Under the same conditions it was shown that GHB does not give rise directly to the corresponding ester when merely in the presence of an alcohol; however the ester will be formed if the conditions are present for conversion of GHB to GBL followed by subsequent reaction with alcohol. In alcoholic beverage samples spiked with GBL the expected conversion to GHB occurred, and the formation of the ethyl ester of GHB was also seen in some samples. Wine samples were analyzed for the presence of the ethyl ester of GHB, and the effect of adding GHB/GBL to hot beverages was studied.     

Determination of endogenous gamma-hydroxybutyric acid (GHB) levels in antemortem urine and blood

Gamma-hydroxybutyric acid's (GHB's) natural presence in the body has made the interpretation of its levels a challenging task for the forensic toxicologist. This study was designed to measure endogenous GHB levels in antemortem urine and blood samples. The range detected in urine was from 34 to 575 microg/dl and in blood from 17 to 151microg/dl. The results indicate that the concentration of endogenous GHB in urine and blood concur with the suggested cut-off levels at 1000 and 500 microg/dl, respectively.     

The extraction and infrared identification of gamma-hydroxybutyric acid (GHB) from aqueous solutions

The chemical analysis of gamma-hydroxybutyric acid (GHB) in most forensic laboratories is complicated by the highly polar nature of the GHB molecule, which makes it unsuitable for direct analysis by gas chromatography (GC). Consequently, a popular analytical approach is to convert GHB into the corresponding lactone or a derivative compound that is then identified by mass spectrometry employed in conjunction with GC (GC/MS). An alternative approach is presented here where GHB may be isolated as a free acid specie from complex aqueous solutions employing a liquid-liquid extraction technique. This approach can yield a relatively pure residue of GHB that presents an infrared transmission spectrum that is sufficiently distinct for identification purposes. Infrared spectroscopy (IR) is a very popular technique that is available to most crime laboratories. The liquid-liquid extraction behavior of GHB is examined in detail and the uniqueness of the infrared spectrum is discussed.     

The presence of gamma-hydroxybutyric acid (GHB) and gamma-butyrolactone (GBL) in alcoholic and non-alcoholic beverages

Gamma-hydroxybutyric acid (GHB) and its precursor gamma-butyrolactone (GBL) are regularly implicated in instances of surreptitious drug administration, particularly in beverages (so-called "spiked drinks"). In order to assist in the interpretation of cases where analysis of the actual beverage is required, over 50 beverages purchased in the UK were analysed for the presence of GHB and GBL. It was found that naturally occurring GHB and GBL were detected in those beverages involving the fermentation of white and particularly red grapes. No GHB or GBL was detected in other drinks such as beer, juice, spirits or liqueurs. GHB/GBL was detected in red wine vermouth (8.2 mg/L), sherry (9.7 mg/L), port (GBL), red wine (4.1-21.4 mg/L) and white wine (<3-9.6 mg/L). The presence of GHB/GBL did not appear to be influenced by the alcohol content or the pH of the beverage. In addition, the concentration in wines did not appear to be related to the geographical origin of the grape type. This is believed to be the first published data concerning the endogenous presence of GHB and GBL in the beverages described.     

化学显色法快速筛选饮料及尿液中γ-羟基丁酸和γ-丁内酯

目的建立化学显色法快速筛选饮料及尿液中γ-羟基丁酸(GHB)及其前体γ-丁内酯(GBL)的方法。方法在酸性条件下GHB转化为GBL,GBL和盐酸羟胺在碱性条件下生成γ-羟基丁酰羟胺,γ-羟基丁酰羟胺在酸性条件下和三氯化铁反应,生成紫红色的络合物。结果饮料中GHB最低检出浓度为0.5～2mg/mL,低于常见滥用质量浓度。该方法也可以用于尿液分析,最低检出质量浓度为0.5mg/mL。考察了常见有机溶剂和麻醉镇静药物的干扰。结论该方法简单、安全、快速,为临床和法庭科学实验室快速筛选GHB和GBL提供了便利。     

Report on the analysis of common beverages spiked with gamma-hydroxybutyric acid (GHB) and gamma-butyrolactone (GBL) using NMR and the PURGE solvent-suppression technique

In forensic evidence, the identification and quantitation of gamma-hydroxybutyric acid (GHB) in "spiked" beverages is challenging. In this report, we present the analysis of common alcoholic beverages found in clubs and bars spiked with gamma-hydroxybutyric acid (GHB) and gamma-butyrolactone (GBL). Our analysis of the spiked beverages consisted of using (1)H NMR with a water suppression method called Presaturation Utilizing Relaxation Gradients and Echoes (PURGE). The following beverages were analyzed: water, 10% ethanol in water, vodka-cranberry juice, rum and coke, gin and tonic, whisky and diet coke, white wine, red wine, and beer. The PURGE method allowed for the direct identification and quantitation of both compounds in all beverages except red and white wine where small interferences prevented accurate quantitation. The NMR method presented in this paper utilizes PURGE water suppression. Thanks to the use of a capillary internal standard, the method is fast, non-destructive, sensitive and requires no sample preparation which could disrupt the equilibrium between GHB and GBL.     

Analysis of gamma-hydroxybutyric acid (GHB) in spiked water and beverage samples using solid phase microextraction (SPME) on fiber derivatization/gas chromatography-mass spectrometry (GC/MS)

Gamma-Hydroxybutyric acid (GHB) is a CNS depressant that has been abused recreationally for its purported euphoric and relaxation effects and for the purposes of drug facilitated sexual assault due to its sedative and amnesic effects at higher doses. The dramatic increase in the abuse of GHB and association in criminal investigations over the past decade has created the need for forensic laboratories to develop analytical methods to detect GHB in a variety of matrices. The method developed in this work used solid-phase microextraction (SPME) to extract GHB from aqueous samples followed by on-fiber derivatization and analysis by gas chromatography/mass spectrometry (GC/MS). This method detected GHB in aqueous matrices with good sensitivity, high precision, excellent linearity from 0.01 mg/mL to 0.25 mg/mL, and without the need for sample manipulation that could cause interconversion between GHB and its lactone, GBL. The method was successfully applied for detection of GHB in spiked water and beverage samples.     

Headspace solid-phase microextraction (HS-SPME) and liquid-liquid extraction (LLE): comparison of the performance in classification of ecstasy tablets. Part 2

Headspace solid-phase microextraction (HS-SPME) is assessed as an alternative to liquid-liquid extraction (LLE) currently used for 3,4-methylenedioxymethampethamine (MDMA) profiling. Both methods were compared evaluating their performance in discriminating and classifying samples. For this purpose 62 different seizures were analysed using both extraction techniques followed by gas chromatography-mass spectroscopy (GC-MS). A previously validated method provided data for HS-SPME, whereas LLE data were collected applying a harmonized methodology developed and used in the European project CHAMP. After suitable pre-treatment, similarities between sample pairs were studied using the Pearson correlation. Both methods enable to distinguish between samples coming from the same pre-tabletting batches and samples coming from different pre-tabletting batches. This finding emphasizes the use of HS-SPME as an effective alternative to LLE, with additional advantages such as sample preparation and a solvent-free process.     

Determination of γ-hydroxybutyrate (GHB) and its precursors in blood and urine samples: A salting-out approach

γ-Hydroxybutyrate (GHB) is an increasingly popular drug of abuse that causes stimulation, euphoria, anxiolysis or hypnosis, depending on the dose used. Low doses of the drug are used recreationally, and also implicated in drug-facilitated sexual assaults. Because of the unusually steep dose–response curves, accidental GHB overdosing, leading to coma, seizures or death can occur. Being a controlled substance, GHB is often substituted with its non-scheduled precursors γ-butyrolactone (GBL) and 1,4-butanediol (BD), which are rapidly metabolized into GHB in the body. Here we describe an assay for GHB, GBL and BD in blood and/or urine samples. GHB and BD were extracted from diluted 200 μL aliquots of samples with t-butylmethylether (plus internal standard benzyl alcohol) in test tubes preloaded with NaCl. After acidification and centrifugation the solvent phase was transferred to a test tube preloaded with Na₂SO₄, incubated for 30 min, centrifuged again, and evaporated in vacuum. The residue was mixed with N-methyl-N-trimethylsilyl-trifluoroacetamide (MSTFA) in acetonitrile, and injected into a GC–MS. When analyzing GBL, the salting-out step was omitted, and analysis was performed with a GC–FID apparatus. As revealed by the validation data this procedure is suitable for quantitative determination of GHB and its precursors in blood and/or urine samples.     

The legal role of medical professionals in decisions to withhold or withdraw life-sustaining treatment: Part 3 (Victoria)

This is the final article in a series of three that examines the legal role of medical professionals in decisions to withhold or withdraw life-sustaining treatment from adults who lack capacity. This article considers the position in Victoria. A review of the law in this State reveals that medical professionals play significant legal roles in these decisions. However, the law is problematic in a number of respects and this is likely to impede medical professionals' legal knowledge in this area. The article examines the level of training that medical professionals receive on issues such as refusal of treatment certificates and substitute decision-making, and the available empirical evidence as to the state of medical professionals' knowledge of the law at the end of life. It concludes that there are gaps in legal knowledge and that law reform is needed in Victoria. The article also draws together themes from the series as a whole, including conclusions about the need for more and better medical education and about law reform generally.     

Identification and quantitation of 3,4-methylenedioxy-N-methylamphetamine (MDMA,ecstasy) in human urine by 1H NMR spectroscopy. Application to five cases of intoxication

Identification of 3,4-methylenedioxy-N-methylamphetamine (MDMA, ecstasy) in five cases of intoxication using nuclear magnetic resonance (NMR) spectroscopy of human urine is reported. A new water suppression technique PURGE (Presaturation Utilizing Relaxation Gradients and Echoes) was used. A calibration curve was obtained using spiked samples. The method gave a linear response (correlation coefficient of 0.992) over the range 0.01–1 mg/mL. Subsequently, quantitation of the amount of MDMA present in the samples was performed. The benefit and reliability of NMR investigations of human urine for cases of intoxication with MDMA are discussed.     

《维也纳条约法公约》第31.3条“任何相关国际法规则”研究

《维也纳条约法公约》第31.3条(c)项在澄清条约模糊、填补空白的同时也留下了诸多疑问:哪些规则具有相关性?适用于当事国间关系的这个短语是否对可以适用的国际法规则的范围具有限制性作用?是否是指条约解释之时处于生效状态的国际法的全部?因此,对第31.3条(c)项立法沿革、用语含义以及相关国际司法实践的探究,对于深入了解国际条约解释规则作用的机理具有积极意义。对时际法性质的理解是审视第31.3条(c)项的一个必要前提。条约解释通常难免借助于其后的相关新条约。     

Sensitive and specific quantification of human genomic deoxyribonucleic acid (DNA) in forensic science specimens: casework examples.

We describe the forensic science application of a method for quantification of human genomic deoxyribonucleic acid (DNA). The two cases cited in this report involve DNA samples extracted from skin tissue and bloodstained clothing recovered from different crime scenes. High-molecular-weight DNA was recovered from both specimens, and the concentrations of these DNAs were estimated to be approximately 0.5 microgram/microL by ethidium bromide/agarose gel electrophoresis. Using the human-specific DNA probe p17H8 (locus D17Z1) to quantify the amount of human genomic DNA in these samples, it is shown that less than 1% of the DNA isolated from the skin tissue is of human origin and that the DNA isolated from the bloodstained clothing is effectively devoid of human DNA sequences. These case examples illustrate the need to quantify not only the total amount of DNA recovered from forensic casework material, but also the proportion of the DNA that is of human origin.     

Skeletal Trauma Resulting From Fatal Low (≤3 m) Free Falls: An Analysis of Fracture Patterns and Morphologies

The skeletal trauma resulting from fatal low (≤3 m) free falls is poorly researched and understood by forensic practitioners. The aim of this study was to identify the types of skeletal trauma resulting from low falls through investigating fracture patterns and morphologies. Skeletal trauma was analyzed using full‐body postmortem computed tomography scans of 145 individuals who died from a low free fall. Trauma was then contextualized to the variables that influence how a person falls using multiple logistic regression. Results showed fracture patterning primarily involved the axial skeleton and that there were a number of patterns significantly associated with the height fallen, pre‐existing health conditions, and age. Analysis of fracture morphologies showed 108 possible fracture types, six of which were significantly associated with the height fallen. Understanding the skeletal trauma characteristic of low free falls will further inform anthropological interpretations of trauma in cases where a fall may be considered the possible mechanism.