Rape Drug Research Articles

Knockout Drugs: Diagnostics in the Emergency Unit and Clinical Practice

Knockout Drugs: Diagnostics in the Emergency Unit and Clinical Practice Abstract. Every now and then, physicians are challenged with date rape drugs. If there is a suspicion of substance administration, the question of involving forensic medicine is commonly raised. In obscure situations or questionable offences, however, patients may wish for an initial diagnosis in the emergency department or the private practice. The physicians are often greatly challenged by the variety of substances, the limited analytical methods and difficulties with the interpretion of results. The major goal of this article is to present diagnostic options including their limitations. An overview of frequently involved substances is provided. Particular focus will be placed on practical aspects, including questions regarding pre-analytics and health insurance coverage.

Date Rape Drugs in Las Vegas: Detection After the Fact [11I

INTRODUCTION: Date rape drugs (DRDs) are drugs which can be used to conduct drug-facilitated sexual assault. The three major drugs classified by the U.S Department of Health & Human Services misused for this purpose are Rohypnol (Flunitrazepam), Gamma hydroxybutyric acid (GHB) and Ketamine. Existing studies in the literature analyze self-reported incidents in women which likely underestimate the prevalence of this problem. Our study aimed to evaluate how frequently there was clinical or criminal suspicion of DRD use prior to autopsy evaluation in a group of deceased DRD positive women. METHODS: This study was a retrospective analysis of all female decedents aged 20-55 who tested positive for Flunitrazepam, GHB and Ketamine referred to the Clark County medical examiner from 2000-2015. Medical records, police report, and autopsy findings were reviewed. All decedents underwent standard toxicology screening from whole blood toxicology analysis. Statistical analysis was performed using student t-test for continuous variables and chi-square for categorical variables. RESULTS: 23 women referred to the Clark County medical examiner tested positive for DRDs. At autopsy 6 women were positive for Rohypnol, 15 for GHB, and 2 for ketamine. After clinical, autopsy and police report review, 74% of 17/23 women had no clinical suspicion of DRD involvement at the time of death. Specifically, 83% (n=5) women had no suspicion of flunitrazepam use prior to toxicology results. CONCLUSION: Only a small minority of cases raised suspicion of DRD use upon police or clinical assessment. DRD use may be more prevalent in society than previously thought posing a significant public health threat.

A paper-based, cell-free biosensor system for the detection of heavy metals and date rape drugs.

Biosensors have emerged as a valuable tool with high specificity and sensitivity for fast and reliable detection of hazardous substances in drinking water. Numerous substances have been addressed using synthetic biology approaches. However, many proposed biosensors are based on living, genetically modified organisms and are therefore limited in shelf life, usability and biosafety. We addressed these issues by the construction of an extensible, cell-free biosensor. Storage is possible through freeze drying on paper. Following the addition of an aqueous sample, a highly efficient cell-free protein synthesis (CFPS) reaction is initiated. Specific allosteric transcription factors modulate the expression of ‘superfolder’ green fluorescent protein (sfGFP) depending on the presence of the substance of interest. The resulting fluorescence intensities are analyzed with a conventional smartphone accompanied by simple and cheap light filters. An ordinary differential equitation (ODE) model of the biosensors was developed, which enabled prediction and optimization of performance. With an optimized cell-free biosensor based on the Shigella flexneri MerR transcriptional activator, detection of 6 μg/L Hg(II) ions in water was achieved. Furthermore, a completely new biosensor for the detection of gamma-hydroxybutyrate (GHB), a substance used as date-rape drug, was established by employing the naturally occurring transcriptional repressor BlcR from Agrobacterium tumefaciens.

GHB receptors - a new trend in psychopharmacology?

Abstract Introduction: Gamma-hydroxybutyric acid (GHB) is commonly known as a recreation drug or the so-called “date rape drug”. It is also used in medicine to treat narcolepsy and alcohol addiction. GHB has an affinity for two types of receptors: GABAB and the relatively recently discovered GHB receptors. GHB receptors were first cloned in 2003 in mice and then in 2007 in humans. So far, evidence has been presented for their impact on dopaminergic transmission, which may imply that they play a role in the pathogenesis of diseases such as schizophrenia. At the same time, it has been demonstrated that benzamide antipsychotic drugs have an affinity for GHB receptors, which is why it is postulated that some of the effects of these drugs may result precisely from this affinity. Aim: The study presents the current state of knowledge about GHB receptors and their potential role in the pathogenesis of schizophrenia, and discusses drugs which show an affinity for this receptor. Material and method: The literature review was based on a search of articles indexed between 1965 and 2018 in Medline, Google Scholar, ScienceDirect and Research Gate databases. The following search terms were used: GHB receptor, GHB, sulpiride, and amisulpride. Result and discussion: 1. It is possible that GHB receptors are involved in the pathogenesis of schizophrenia, although more research is needed in this area. 2. Part of the effects of some benzamide antipsychotic drugs (such as amisulpride) may be due to their affinity for GHB receptors.

Naked-eye quantitative assay on paper device for date rape drug sensing via smart phone APP

The present work aimed for the development of a low-cost, naked eye assay indicating the presence of date-rape drug (DRD) in the alcoholic beverages. A microfluidic paper-based analytical device (μPAD) was used as the platform to prepare this sensor. Bromocresol green (BCG; 0.04% and 5%) was used as the indicator for the colorimetric assay of DRD,.i.e., ketamine. The developed paper based strip was coated with BCG and further ketamine solution. The complexation between dye and drug lead to the change in color of the strip. The color also varied upon change in the concentration of ketamine (0.1 M, 0.01 M, 0.001 M) in the solution which forms the basis of the detection. The color change of BCG at 0.04% was not much detectable, therefore, 5% BCG concentration was chosen for development of the colorimetric sensor. The device was linked with a smart phone app which depicts the change in color and displays whether the beverage is safe or unsafe for drinking. In addition, the app sends message to selected number, if the person is in danger.

A contemporary facet on rohypnol: a date rape drug

A contemporary facet on rohypnol: a date rape drug

A contemporary facet on rohypnol: a date rape drug

A contemporary facet on rohypnol: a date rape drug

Forensic Identification of Sexual Assault by use of Date Rape Drugs

Forensic Identification of Sexual Assault by use of Date Rape Drugs

Alterations in gene expression after gamma-hydroxybutyric acid intake-A pilot study.

Gamma-hydroxybutyric acid (GHB) acts as an agonist of the GABAB receptor, where GHB induces a depressant effect in the central nervous system. Besides its therapeutic application, GHB is also used as a date rape drug. However, the detection of GHB ingestion proves to be difficult due to its narrow detection window. The aim of this pilot study was to assess differential gene expressions after GHB intake to identify potential biomarkers for the detection of GHB intake. To this aim, alteration in gene expression of ALDH5A1, AKR7A2, EREG, and PEA15 was investigated via quantitative PCR (qPCR). Data normalization was based on a previously established and empirically derived normalization strategy. Blood samples of patients (n=3) therapeutically taking sodium oxybate solution (GHB) and of donors without GHB intake (n=49) were analyzed and compared. All qPCR procedures and results are reported according to the MIQE guidelines. Investigation of suitable reference genes using established algorithms suggested PPIB and FPGS as best-suited normalizers. Alterations in gene expression relating to GHB intake could not be confirmed to a forensically sufficient degree. However, significant differences in expression of EREG in the control group were observed, when time-point of sample collection was considered, indicating circadian rhythm. The study's main limitation is the small number of study subjects. Herein, we are first to present an empirically derived strategy for a robust normalization of qPCR data from the analysis of GHB-induced gene expression in human blood. We present results of the analysis of differential expression of ALDH5A1, AKR7A2, EREG, and PEA15 in the GHB-negative population. Finally, we report our findings on the effect of GHB intake on the expression of these genes and their presumable potential as GHB biomarkers.

Point of Care with Micro Fluidic Paper Based Device Incorporated with Nanocrys of Zeolite –GO for Electrochemical Sensing of Date Rape Drug

The objective of the present invention is to develop an ultrasensitive technique for the electro analysis of rape drug. A paper chip (EμPADs) was developed using nanocrystals (Nanocrys) of graphene-oxide and zeolites (Zeo-GO). Nanocrys modified EμPAD showed wide linear range 0.001 - 5 nM/ml and low detection limit of 0.00002 nM/ml. The developed sensor was tested in real time samples like alcoholic and non-alcoholic drinks and found good correlation (99%). Extensive development can be made for industrial translation of this fabricated device.

Point of care with micro fluidic paper based device integrated with nano zeolite–graphene oxide nanoflakes for electrochemical sensing of ketamine

The present study was aimed to develop an ultrasensitive technique for electroanalysis of ketamine; a date rape drug. It involved the fabrication of nano-hybrid based electrochemical micro fluidic paper-based analytical device (EμPADs) for electrochemical sensing of ketamine. A paper chip was developed using zeolites nanoflakes and graphene-oxide nanocrystals (Zeo–GO). EμPAD offers many advantages such as facile approach, economical and potential for commercialization. Nanocrystal modified EμPAD showed wide linear range 0.001–5nM/mL and a very low detection limit of 0.001nM/mL. The developed sensor was tested in real time samples like alcoholic and non-alcoholic drinks and found good correlation (99%). The hyphenation of EμPAD integrated with nanocrystalline Zeo–GO for detection of ketamine has immense prospective for field-testing platforms. An extensive development could be made for industrial translation of this fabricated device.

Male victims of sexual assault; 10 years' experience from a Danish Assault Center

This study aims to provide descriptive data regarding male victims of sexual assault seen at the Centre for Victims of Sexual Assault in Copenhagen, Denmark. All 55 male victims attending the center in the time period of March 2001 until December 2010 underwent a standardized data collection. Data included information on the victim and the sexual assault. Male victims accounted for less than 2% of the total number of visits to the center in this time period. Fifty three percent were between 15 and 24 years. In all cases the perpetrator was male, and 25% were assaulted by more than one perpetrator. Of the 62% of male victims who gave information on sexual orientation, 36% reported themselves as heterosexuals. A total of 45.5% had an alcohol intake of more than 5 units in the hours before the assault. Forty two percent reported the assault to the police. The male victims differed from female victims in several ways; they were more often assaulted by a stranger; more likely to be assaulted by more than one perpetrator; more likely being victim of drug rape; less likely to have experienced previous sexual abuse and less willing to report their assault to the police. Being victim of a sexual assault by another man is considered a taboo subject and it is likely that the dark figure of men exposed to sexual assault is much higher than it is for women. Strengthening our knowledge regarding male victims of sexual assault is necessary to improve both primary and secondary preventive measures in order to make male victims feel safe in coming forward. Male victims should have equal access to both medical and psychological help as female victims.

The Effect of Flunitrazepam (Rohypnol(®) ) on the Development of Chrysomya megacephala (Fabricius, 1794) (Diptera: Calliphoridae) and its Implications for Forensic Entomology.

This study investigated the potential effects of flunitrazepam (known as "date rape drug") on the developmental cycle of Chrysomya megacephala, an important forensic species, and their possible implications for the calculation of the PMI. A 1050 C.megacephala eggs were divided into five groups with seven replications each. The eggs were placed on artificial diet prepared with four drug concentrations of flunitrazepam (4, 8, 16, and 32ng/g), besides the control group (prepared with water). Were evaluated the potential effects on development time, weight gain, and mortality during the cycles. The drug had no significant effect on development time or mortality although it did affect the weight of the pupae and adults (Kruskal-Wallis, p<0.05). The result can be deduced that the determination of the postmortem interval is not affected.

Simultaneous analysis method for GHB, ketamine, norketamine, phenobarbital, thiopental, zolpidem, zopiclone and phenytoin in urine, using C18 poroshell column.

Date-rape drugs have the potential to be used in drug-facilitated sexual assault, organ theft and property theft. Since they are colorless, tasteless and odorless, victims can drink without noticing, when added to the beverages. These drugs must be detected in time, before they are cleared up from the biofluids. A simultaneous extraction and determination method in urine for GHB, ketamine, norketamine, phenobarbital, thiopental, zolpidem, zopiclone and phenytoin (an anticonvulsant and antiepileptic drug) with LC-MS/MS was developed for the first time with analytically acceptable recoveries and validated. A 4 steps liquid-liquid extraction was applied, using only 1.000mL urine. A new age commercial C18 poroshell column with high column efficiency was used for LC-MS/MS analysis with a fast isocratic elution as 5.5min. A new MS transition were introduced for barbital. 222.7>179.8 with the effect of acetonitrile. Recoveries (%) were between 80.98-99.27 for all analytes, except for GHB which was 71.46. LOD and LOQ values were found in the ranges of 0.59-49.50 and 9.20-80.80ngmL(-1) for all the analytes (except for GHB:3.44 and 6.00μgmL(-1)). HorRat values calculated (between 0.25-1.21), revealed that the inter-day and interanalist precisions (RSD%≤14.54%) acceptable. The simultaneous extraction and determination of these 8 analytes in urine is challenging because of the difficulty arising from the different chemical properties of some. Since the procedure can extract drugs from a wide range of polarity and pKa, it increases the window of detection. Group representatives from barbiturates, z-drugs, ketamine, phenytoin and polar acidic drugs (GHB) have been successfully analyzed in this study with low detection limits. The method is important from the point of determining the combined or single use of these drugs in crimes and finding out the reasons of deaths related to these drugs.

Triazolam Impairs Avoidance Reaction-A Scientific Proof Why the Victim does not Escape from Drug-Facilitated Sexual Assaults

Following closely behind levels in Western countries, the number of drug-facilitated sexual assaults (DFSAs), involving the illicit use of medicine, has been recently increasing in Japan. Tirazolam is the most frequently used date-rape drug in DFSAs occurring in Japan. In this study, the effect of triazolam on behavior in response to fear and anxiety was evaluated using an elevated plus-maze test in mice. Triazolam-treated animals (0.01 mg/kg) showed no significant difference in total locomotor activity compared with vehicle-treated mice (controls). On the contrary, activity levels on the open arms of the apparatus (time spent, mean value of movement), where mice would normally feel anxiety or fear, were significantly increased in triazolam-treated mice compared with controls. However, total locomotor activities on the plus-maze were not different between two groups, indicating that sedation was not induced by tirazolam under these conditions. These results suggest that triazolam treatment led the mice to become insensitive to fear and anxiety; their defence reactions were impaired. We conclude that this finding provides scientific evidence in reply to defence arguments presented in court trials that there is little or no evidence of the victim attempting to escape from a sexual assault. Additionally, the finding is as true of other benzodiazepine receptor agonists as of triazolam.

Determination of endogenous concentration of γ-hydroxybutyric acid (GHB) in hair through an ad hoc GC–MS analysis: A study on a wide population and influence of gender and age

γ-Hydroxybutyric acid (GHB) spread for recreational purposes or as “rape drug” represents a hard issue for forensic toxicologists due to its endogenous nature. It is clear that an actual and reliable discrimination between basal and exogenous levels is mandatory to achieve a correct evaluation of conscious/unconscious administration. This research aimed to study the GHB baseline in hair samples, collected from 150 volunteers, non-consumers of any drugs of abuse, in order to evaluate if a generic cut-off value could be accepted, also focusing on potential influences of gender and age. The analysis consisted of an overnight incubation with NaOH at 56°C, liquid–liquid extraction with ethylacetate and trimethylsylil derivatization. Detection was carried out through gas chromatography-mass spectrometry in single ion monitoring (m/z 233, 234, 147 for GHB; m/z 239, 240 and 147 for GHB-d6). The endogenous amount in “blank” hair was estimated by the standard addition method. Concentration range was 0.279–2.839ng/mg. In males, the average GHB levels were higher than in females (0.829 vs 0.596ng/mg, respectively), especially in the first age category (<30 years, 1.008 vs 0.606ng/mg, respectively). Age influences on GHB levels seemed to be different among the two sexes: in male population concentrations were higher <30 (1.008ng/mg) and similar in the other age ranges (0.762ng/mg, 30–50; 0.763ng/mg, >50); in female, quite similar levels were registered throughout all the age categories (0.606ng/mg, <30; 0.536ng/mg, 30–50; 0.691ng/mg, >50). Further study should be performed on GHB physiology in order to better understand these differences among ages and genders. Moreover, we demonstrated that for hair analysis a cut-off reference value is not strictly mandatory, underlining the great interpretative valence of segmental analysis.

Analysis of γ-hydroxy butyrate by combining capillary electrophoresis-indirect detection and wall dynamic coating: application to dried matrices.

γ-Hydroxybutyric acid (GHB) is a powerful central nervous system depressant, currently used in medicine for the treatment of narcolepsy and alcohol dependence. In recent years, it has gained popularity among illegal club drugs, mainly because of its euphoric effects as well as doping agent and date rape drug. The purpose of the present work was the development of a rapid analytical method for the analysis of GHB in innovative biological matrices, namely dried blood spots (DBSs) and dried urine spots (DUSs). The analytical method is based on capillary zone electrophoresis with indirect UV absorption detection at 210nm and capillary wall dynamic coating. The background electrolyte is composed of a phosphate buffer containing nicotinic acid (probe for detection) and cetyltrimethylammonium bromide (CTAB, reversal of electroosmosis in wall dynamic coating). The influence of probe and CTAB concentration, together with buffer pH, on migration time and signal response was investigated. Under the optimized conditions, analytical linearity and precision were satisfactory; absolute recovery values were also high (>90%); the use of dried matrices (DBSs and DUSs) was advantageous as an alternative matrix to classical ones. No interferences were found either from the most common exogenous or from endogenous compounds. This analytical approach can offer a rapid, precise and accurate method for GHB determination in innovative biological samples, which could be important for screening purposes in clinical and forensic toxicology. Graphical Abstract CE method, by combined indirect UV detection and dynamic coating, for GHB determination in DBSs and DUSs.

Scientist Nabbed On Drug Charges

Kurt Romondt, a chemical engineer who works for pharmaceutical firm Merck & Co., has been arrested and charged with making γ-hydroxybutyric acid, a party drug known as GHB, in his New Jersey home. According to the prosecutor’s office for Union County, N.J., Romondt, 44, was arrested and jailed on June 18, after he received a delivery of γ-butyrolactone, an industrial solvent used to synthesize GHB. A search of his home turned up 300 mL of the drug and 2,745 g of its precursor along with a scale and materials to process the drug. GHB is a controlled substance that can be used to treat narcolepsy, a sleep disorder, and alcohol addiction. With street names such as Fantasy and Liquid G, GHB has been used to produce euphoric effects since the 1990s. Large doses have a sedative effect, leading to the labeling of GHB as a date-rape drug. The prosecutor’s office ...

Screening for Selected Club Drugs Utilizing LC/MS Direct Urine Analysis

A simple liquid chromatography mass spectrometric method with direct urine injection analysis was developed and validated for the identification and quantification of gammahydroxybutyric acid (GHB), gamma-butyrolactone (GBL), 1,4-butanediol (1,4-BD), methylenedioxyn- methylamphetamine (MDMA), 3,4-methylenedioxy-amphetamine (MDA), 3,4-methylenedioxy-Nethylamphetamine (MDEA), ketamine (KET) and norketamine (Nor-KET). GHB-d6, GBL-d6, MDMA-d5, and KET-d4 were used as internal standards (IS). The method has the advantage of one step sample preparation which includes an appropriate dilution and filtration before its injection into the LC/MS system. The protonated ions of the analytes were detected and quantified using an ESI probe operating in positive mode and selected ion monitoring (SIM). The linear range was between 8-20 μg/mL for GHB, GBL and 1,4-BD, 50- 1000 ng/mL for MDEA, KET and Nor-KET and 250-1000 ng/mL for MDMA and MDA, providing square correlation coefficient (r2) ≥ 0.98. Interday and intraday errors were found to be ≤ 13.53%. The applicability of the proposed direct injection LC/MS method was confirmed with the analysis of ten authentic samples initially tested for amphetamines through a preliminary immunoassay screening. In addition, eight samples were assayed for KET and Nor-KET and six samples for GHB, GBL and 1,4-BD. The method is simple, accurate and possesses better specificity comparing to the immunoassay techniques, which make it suitable for screening purposes. It also presents the same or lower cost comparing to the respective immunoassay kit, where available. Toxicological laboratories may use the proposed method, overcoming thus the appeared false positive results (amphetamines) or the absence of immunoassay kits (GHB, GBL, 1,4-BD, KET, Nor-KET), avoiding also the use of increased cost instrumentation such as a liquid chromatography tandem mass spectrometry. Keywords: Amphetamines, date-rape drugs, GHB, ketamine, mass spectrometry, urine.

Metabolism of gamma hydroxybutyrate in human hepatoma HepG2 cells by the aldo-keto reductase AKR1A1

Gamma hydroxybutyrate (GHB) is a recreational and date-rape drug, for which the detection following ingestion is hampered by rapid metabolism and its endogenous presence. GHB catabolism occurs mainly by its oxidation to succinic semialdehyde (SSA), which converts to succinate and enters the tricarboxylic acid cycle. A high Km aldehyde reductase has previously been reported to catalyse the NADP-dependent oxidation of GHB at high concentrations. It is assumed that this enzyme is identical to the aldo-keto reductase AKR1A1, but its role in GHB oxidation has not been fully evaluated.In this study, the extent of AKR1A1 in GHB metabolism has been determined in HepG2 cells using RNA-interference technology. The gene encoding AKR1A1 was targeted by siRNA. Results demonstrate a successful knock-down of the AKR1A1 gene with 92% reduction in total mRNA and 93% reduction in protein expression. Demolishing AKR1A1 expression in HepG2 cells leads to significant 82% decrease in NADP-dependent GHB-dehydrogenase activity at high concentration (10mM) of GHB. Moreover, when exposing the cells to 50μM of GHB for 24h, and measuring intracellular and extracellular GHB levels by GC/MS, a significant two-fold increase was observed on GHB intracellular level in silenced cells. In contrast, measuring SSA-reductase activity in silenced cells indicated that AKR1A1 is not involved in endogenous GHB production. These findings describe a pathway for GHB metabolism in the liver which should be useful in GHB exposure cases, and will enable a better understanding of the enzymes participating in its metabolism at natural and overexposed levels.