Drug-facilitated Sexual Assault Research Articles

Pharmacokinetics of GHB and detection window in serum and urine after single uptake of a low dose of GBL – an experiment with two volunteers

During the last few years γ-hydroxybutyric acid (GHB) and γ-butyrolactone (GBL) have attracted much interest as recreational drugs and knock-out drops in drug-facilitated sexual assaults. This experiment aims at getting an insight into the pharmacokinetics of GHB after intake of GBL. Therefore Two volunteers took a single dose of 1.5 ml GBL, which had been spiked to a soft drink. Assuming that GBL was completely metabolized to GHB, the corresponding amount of GHB was 2.1 g. Blood and urine samples were collected 5 h and 24 h after ingestion, respectively. Additionally, hair samples (head hair and beard hair) were taken within four to five weeks after intake of GBL. Samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after protein precipitation with acetonitrile. The following observations were made: spiked to a soft drink, GBL, which tastes very bitter, formed a liquid layer at the bottom of the glass, only disappearing when stirring. Both volunteers reported weak central effects after approximately 15 min, which disappeared completely half an hour later. Maximum concentrations of GHB in serum were measured after 20 min (95 µg/ml and 106 µg/ml). Already after 4-5 h the GHB concentrations in serum decreased below 1 µg/ml. In urine maximum GHB concentrations (140 µg/ml and 120 µg/ml) were measured after 1-2 h, and decreased to less than 1 µg/ml within 8-10 h. The ratio of GHB in serum versus blood was 1.2 and 1.6.

Desalkylflurazepam found in patients’ samples after high‐dose midazolam treatment

In forensic cases, for example, cases of Munchhausen-by-proxy or drug-facilitated sexual assault, the clarification of the origin of detected drugs, even if they are present in trace levels only, is important. For this purpose liquid chromatography-tandem mass spectrometry (LC-MS/ MS) or gas chromatography-mass spectrometry (GC-MS) methods have been developed for forensic toxicological analyses, which can be used besides more traditional screening procedures. For analysis of benzodiazepines and some of their metabolites in blood/ serum and urine, a comprehensive LC-MS/MS method was used. Midazolam is a narcotic drug with a half-life of 1.5 to 3 h in adults and 0.8 to 1.8 h in children over 12 months. It is applied mainly in emergency cases, in intensive care units, and before or during surgery. Flurazepam is a hypnotic drug, used as sleeping pill, which is rapidly metabolized during the first pass through the liver. Hence, blood and urine concentrations of the unchanged drug are low. The major metabolites in blood are desalkylflurazepam and 2-OHethylflurazepam, which are both pharmacologically active and accumulate when administered on a regular basis. Steady state concentrations of desalkylflurazepam after daily oral doses of 15 mg flurazepam were reported to range from 30 to 150 mg/L. The half-life of flurazepam is approximately 2 h. Desalkylflurazepam shows a significantly longer half-life of 74 24 h.

Hair as an Alternative Matrix in Bioanalysis

Alternative matrices are steadily gaining recognition as biological samples for toxicological analyses. Hair presents many advantages over traditional matrices, such as urine and blood, since it provides retrospective information regarding drug exposure, can distinguish between chronic and acute or recent drug use by segmental analysis, is easy to obtain, and has considerable stability for long periods of time. For this reason, it has been employed in a wide variety of contexts, namely to evaluate workplace drug exposure, drug-facilitated sexual assault, pre-natal drug exposure, anti-doping control, pharmacological monitoring and alcohol abuse. In this article, issues concerning hair structure, collection, storage and analysis are reviewed. The mechanisms of drug incorporation into hair are briefly discussed. Analytical techniques for simultaneous drug quantification in hair are addressed. Finally, representative examples of drug quantification using hair are summarized, emphasizing its potentialities and limitations as an alternative biological matrix for toxicological analyses.

UHPLC‐MS/MS and UHPLC‐HRMS identification of zolpidem and zopiclone main urinary metabolites and method development for their toxicological determination

Zolpidem and zopiclone (Z-compounds) are non-benzodiazepine hypnotics of new generation that can be used in drug-facilitated sexual assault (DFSA). Their determination in biological fluids, mainly urine, is of primary importance; nevertheless, although they are excreted almost entirely as metabolites, available methods deal mainly with the determination of the unmetabolized drug. This paper describes a method for the determination in urine of Z-compounds and their metabolites by ultra-high-pressure liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) and UHPLC coupled with high resolution/high accuracy Orbitrap® mass spectrometry (UHPLC-HRMS). The metabolic profile was studied on real samples collected from subjects in therapy with zolpidem or zopiclone; the main urinary metabolites were identified and their MS behaviour studied by MS/MS and HRMS. Two carboxy- and three hydroxy- metabolites, that could be also detected by gas chromatography/mass spectrometry (GC-MS) as trimethylsylyl derivatives, have been identified for zolpidem. Also, at least one dihydroxilated metabolite was detected. As for zopiclone, the two main metabolites detected were N-demethyl and N-oxide zopiclone. For both substances, the unmetabolized compounds were excreted in low amounts in urine. In consideration of these data, a UHPLC-MS/MS method for the determination of Z-compounds and their main metabolites after isotopic dilution with deuterated analogues of zolpidem and zopiclone and direct injection of urine samples was set up. The proposed UHPLC-MS/MS method appears to be practically applicable for the analysis of urine samples in analytical and forensic toxicology cases, as well as in cases of suspected DFSA.

Uptake of Gamma-Valerolactone--Detection of Gamma-Hydroxyvaleric Acid in Human Urine Samples

Gamma-valerolactone (GVL) is reported to be a substance that can be used as a legal substitute for gamma-hydroxybutyric acid (GHB), which is currently a controlled substance in several countries. Unlike gamma-butyrolactone and 1,4-butanediol, GVL is not metabolized to GHB, which causes the effects after uptake of these two chemicals. In the case of GVL, the lactone ring is split to gamma-hydroxyvaleric acid (GHV or 4-methyl-GHB) by a lactonase. Because of its affinity for the GHB receptor, GHV reveals similar effects to GHB, although it is less potent. Intoxications with GVL, or its use as a date rape drug, are conceivable. Despite these facts, there are no publications in the literature regarding detections of GHV in human samples. This study reports three cases, including five urine samples, in which GHV could be detected in concentrations between 3 and 5.8 mg/L. In one of these cases, a drug-facilitated sexual assault (DFSA) was assumed; four of these samples were from two people suspected of abusing GHB. The results indicate that GVL is used as an alternative to GHB and its precursors and should be taken seriously. GVL or GHV should be included in toxicological analysis, particularly in DFSA cases. More information is needed regarding the pharmacokinetics of GVL/GHV for the meaningful interpretation of positive or negative results.

Measurement of drug facilitated sexual assault agents in simulated sweat by ion mobility spectrometry

Ion mobility spectrometry has found widespread use for the detection of explosives and illicit drugs. The technique offers rapid results with high sensitivity and little sample preparation. As such, it is well suited for field deployed screening settings. Here the response of ion mobility spectrometers for three drug-facilitated sexual assault (DFSA) agents – flunitrazepam, ketamine, and MDMA – and related metabolites has been studied in the presence of a simulated sweat. While all three DFSA agents present certain challenges for qualitative identification, IMS can provide useful information to guide the early treatment and investigation of sexual assault cases. Used as a presumptive test, the identification of DFSA agents would later require confirmatory analysis by other techniques.

GHB acid: A rage or reprive

Gamma-hydroxybutyric acid (GHB) is a naturally occurring analog of gamma-aminobutyric acid (GABA) that has been used in research and clinical medicine for many years. GHB was used clinically as an anesthetic in the 1960s but was withdrawn due to side effects that included seizures and coma. GHB has been implicated in a number of crime types; most notably in drug-facilitated sexual assault. GHB is abused by three main groups of users: Body builders who use the substance believing that it stimulated the release of growth hormone; sexual predators who covertly administer the drug for its sedative and amnesic effects and club-goers (rave parties) who take the drug for its euphoric effects. The short-lived hypnotic effects, relative safety and widespread availability of the drug have made it particularly well suited to this role. The drug has an addictive potential if used for long term. The primary effects of GHB use are those of a CNS depressant and therefore range from relaxation, to euphoria, confusion, amnesia, hallucinations, and coma. Despite the increased regulation, GHB remains widely available through the Internet where one can easily purchase the necessary reagents as well as recipes for home production. There are reports of patients being unresponsive to painful stimuli and cases of oral self-mutilations linked to the abuse of GHB, though quiet rare. Such cases should remind odontologists that intra-oral lesions may be the result of self-mutilation either due to mental illness or altered states caused by the use of prescription or non-prescription drugs.

Development of a fluorescent sensor for an illicit date rape drug – GBL

The first fluorescent sensor for an illicit date rape drug, GBL, was developed and named Green Date. It shows high fluorescence enhancement to GBL and allows its detection in different drinks. The mechanism between GBL and Green Date was explored. This discovery may help to prevent the drug-facilitated sexual assault problems.

A Case of Drug-Facilitated Sexual Assault Involving 3,4-methylene-dioxy-methylamphetamine

Typical scenarios of drug-facilitated sexual assaults usually involve victims having ingested a drink after which they had little, partial or no recollection of events for a period of time. We were surprised by the case of a woman who was sexually assaulted and described a state of amazement, leading to an incapacity to resist physically or verbally to her aggressor, and who remembered everything. Alcohol was first suspected but toxicological analysis revealed the presence of 3,4-methylene-dioxy-methylamphetamine (MDMA, Ecstasy). In the literature review, a few cases of sexual assault involving involuntarily MDMA intake are described.

Treating the Psychological Sequelae of Proactive Drug-Facilitated Sexual Assault: Knowledge Building Through Systematic Case Based Research

Drug-facilitated sexual assault (DFSA) has emerged as a distinct category of sexual victimization and precipitates posttraumatic stress disorder (PTSD). Few studies have examined the distinct psychological aspects of PTSD caused by DFSA. Gauntlett-Gilbert, Keegan and Petrak (2004) represent a notable exception and draw on cases, from their clinical experience, treated using Ehlers and Clarks' (2000) cognitive therapy (CT). This paper aims to further develop and refine clinical knowledge on CT for PTSD arising from DFSA and advance the findings of Gauntlett-Gilbert et al. (2004). Systematic case based research was used to investigate the applicability of CT for PTSD related to DFSA. Three survivors were treated with CT within the South African context. The case series corroborated existing findings but also documented the presence of somatic and visual intrusions among survivors with partial or complete amnesia for rape and illustrated the utility of imagery interventions in targeting intrusions. The study highlighted the role of physical paralysis in DFSA in compounding helplessness/powerlessness and the necessity of enhancing physical agency and building social support. Distinctive aspects of PTSD related to DFSA can be effectively treated by adapting CT to suit this population group.

Monitoring of the interconversion of gamma‐butyrolactone (GBL) to gamma hydroxybutyric acid (GHB) by Raman spectroscopy

Gamma-hydroxybutyric acid (GHB) is a drug-of-abuse that has recently become associated with drug-facilitated sexual assault, known as date rape. For this reason the drug is commonly found 'spiked' in alcoholic beverages. When GHB is in solution it may undergo conversion into the corresponding lactone, Gamma-butyrolactone (GBL). Studies have been carried out to determine the detection limits of GHB and GBL in various solutions by Raman spectroscopy and to monitor the interconversion of GHB and GBL in solution with different pH conditions and temperature. In this study, a portable Raman spectrometer was used to study the interconversion of GHB and GBL in water and ethanol solutions as a function of pH, time, and temperature. The aim of this was to determine the optimum pH range for conversion in order to relate this to the pH ranges that the drug is likely to be subjected to, first in spiked beverages and secondly after ingestion in the digestive system. The aim was also to identify a timescale for this conversion in relation to possible scenarios, for example if GHB takes a number of hours to convert to GBL, it is likely for the beverage to be ingested before esterification can take place. GHB and GBL were then spiked into a selection of beverages of known pH in order to study the stability of GHB and GBL in real systems.

Fast screening of 88 pharmaceutical drugs and metabolites in whole blood by ultrahigh-performance liquid chromatography–tandem mass spectrometry

Forensic investigations involving acute or lethal intoxication, drug-facilitated sexual assault, driving or workplace impairment frequently require the analysis of fresh or postmortem blood samples to check out a wide variety of pharmaceutical and illicit drugs, even after single-dose consumption. A sensitive and selective ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) screening method was developed for fast screening of 88 psychoactive drugs and metabolites in blood samples, including the ones most frequently involved in acute intoxications and forensic investigations in Italy. The new method allows short sample processing and analysis time (the whole procedure can be accomplished in less than 30 min) together with the simultaneous monitoring of a large number of pharmaceutical substances. These features represent crucial factors in the approach of acute intoxications, when the patient requires urgent and appropriate therapy. Blood sample treatment was limited to protein precipitation. Two UHPLC-MS/MS runs in positive and negative electrospray ionization modes were performed. The data were acquired at unit mass resolution in the selected reaction monitoring mode. According to international guidelines, linearity range, precision, trueness, detection and quantification limits, recovery, selectivity, specificity, carryover, and matrix effect phenomena were determined. Despite the limited sample purification and the inherent decreased chance of eliminating any potential interference, the present multiresidue screening method proved extremely effective and sensitive, allowing the detection of all tested drugs, even those belonging to structurally different classes of substances. Moreover, the developed method is easily susceptible to further expansion to encompass more drugs, either new or those becoming important for criminal investigation. This protocol was also applied to the analysis of authentic blood samples collected from victims of various crimes in routine casework, whose relevance in forensic investigations is presented in five cases.

Acute Sexual Assault and Evidence Collection in the DNA Era

Approximately 70 000 reports of sexual abuse in children and adolescents are substantiated each year. Many of these cases present to the emergency department for assessment. Knowledge of which cases require emergent evaluation is essential. This article will provide a description of the steps in the assessment of acute sexual assault in children and adolescents including components of the patient interview, proper interpretation of physical examination findings, indications for sexually transmitted infection screening, and prophylaxis as well as forensic evidence collection, assessment of a drug-facilitated sexual assault, and when a report to child protective services and law enforcement is appropriate. A case of acute sexual assault will be used to illustrate pertinent points.

Prolonged excretion of 7-aminoclonazepam in urine after repeated ingestion of clonazepam: A case report

Urinary analyses of the metabolite 7-aminoclonazepam (7-AC) can be helpful in monitoring drug abuse and in the context of suspected drug-facilitated sexual assaults (DFSA). Only two studies have reported detection times of 7-AC in urine after a single dose of clonazepam, and no previous studies have reported detection times after repeated ingestions of clonazepam.This report describes along detection time of 7-AC in urine in the case of a 28-year-old woman with a two year history of daily drug abuse of heroin and clonazepam, who was admitted to a detoxification unit. Urinary samples were delivered every morning for 9 days. Screening analysis in urine was performed by immunoassay, and confirmation analysis by LC–MS/MS.7-AC was detected for 9 days, and the concentration at day 9 was still high (97ng/ml), compared to previously reported data. These results indicate that after repeated ingestions of clonazepam, 7-AC can possibly be detected for about 2–3 weeks after cessation, applying cut-off levels commonly used in drug testing programs and DFSA cases.

Screening analysis for medicinal drugs and drugs of abuse in whole blood using ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC–TOF-MS)—Toxicological findings in cases of alleged sexual assault

An ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC–TOF-MS) method for simultaneous screening of 46 medicinal drugs and drugs of abuse in whole blood was developed and validated. The method includes most of the commonly used and abused drugs such as amphetamines, cocaine, benzodiazepines, and opioids. Chromatographic separation of the targeted drugs was achieved using a Waters ACQUITY UPLC coupled to a Waters Micromass LCT Premier XE time-of-flight mass spectrometer. The total chromatographic run time was 13.5min injection to injection. The estimated method LOQ is in the range of 0.06–27ng/g, which is below the therapeutic levels for each of the drugs analyzed but LSD. The extraction recovery ranged from 6% to 197% with median value 95% and mean value 82%. Matrix effect ranged from 81% suppression to 29% enhancement of the signals compared to signals obtained in the absence of biological matrix. The method was tested on 55 authentic forensic toxicology samples confirming the same positive results as found using the routine analytical procedures as well as some additional compounds.Recently there has been considerable attention paid to drug-facilitated sexual assault and the toxicological findings in these cases. As part of a pilot study to investigate the prevalence of medicinal drugs, drugs of abuse, and alcohol in victims of alleged sexual assault, biological specimens were obtained from 167 victims being examined at the Sexual Assault Center in Aarhus, Denmark. The obtained blood samples were analyzed using the novel screening method supported by additional analyses for e.g. THC and alcohol. 124 victims reported they have been drinking alcohol prior to the assault (74%). Alcohol analyses revealed 59 positive findings (48%). 35 of the cases were found positive for one or more drugs excluding alcohol (21%). 20 of the victims reported they have been subject to a drug-facilitated sexual assault (12%). For the victims suspecting drug-facilitated sexual assault, the toxicological analyses revealed four positive for alcohol and nine victims were positive for one or more drugs, with six of the victims found positive for benzodiazepines or other drugs with sedative effects. It was notable that victims tested positive for medicinal drugs and drugs of abuse as well as victims of alleged drug-facilitated sexual assault in average underwent medical examination later than the whole study population.

Use of tetrahydrozoline for chemical submission

We report two cases of drug-facilitated sexual assault which presented with CNS depression rendering the victims vulnerable to sexual assault and unable to recall the events surrounding the crimes. In each tetrahydrozoline (THZ) was quantified. Case #1 ingested an unknown amount of eye drops containing THZ mixed with alcoholic beverages. Case #1 presented to the emergency department (ED) approximately 7h after reportedly being sexually assaulted and was without symptoms in the ED. Earlier reports from individuals who saw her indicated the victim to be "heavily intoxicated". Case #2 also ingested an unknown amount of eye drops containing THZ mixed with alcoholic beverages. Case #2 presented to an ED without symptoms approximately 23h after reportedly being sexually assaulted. Urine obtained from both cases was assessed for THZ concentrations using gas-chromatography-mass spectrometry. Case #1 had a 0.15g% (by weight by volume) urine ethanol concentration and a urinary THZ concentration of 1.481ng/ml, approximately 7h after ingestion. Case #2 was negative for ethanol but had a urine THZ concentration of 108ng/ml at 23h post-ingestion. Few case reports have been published documenting the use of THZ to facilitate sexual assault. We report two cases of drug-facilitated sexual assault involving the use of THZ where alcoholic beverages were concomitantly consumed. This is the first paper to our knowledge which discusses pharmacology of THZ ingestion and the significance of alcohol being present.

Pharmacokinetic Properties of -Hydroxybutyrate (GHB) in Whole Blood, Serum, and Urine

Over the last 10-15 years, γ-hydroxybutyrate (GHB) and γ-butyrolactone have become increasingly popular "club drugs", but they have also gained attention as potential agents of drug-facilitated sexual assault (DFSA). Several studies have attempted to characterize GHB's pharmacokinetic properties in humans, and the aim of this paper is to build on this research with an emphasis on DFSA cases. A 25 mg/kg dose of GHB was given to 12 GHB-naïve volunteers (6 men and 6 women). Urine and blood samples (serum and whole blood) were collected and analyzed by gas chromatography-mass spectrometry following liquid-liquid extraction. The urinary T(max) was 1 h in 11 volunteers with a mean C(max) of 67.6 mg/L (32.6-161.3 mg/L). Urinary concentrations rapidly decreased to < 10 mg/L (interpretive limit) for 11 volunteers after just 4 h. Data derived from whole blood (mean C(max) = 48.0 mg/L, T(max) = 24.6 min) closely matched that from serum (mean C(max) = 59.4 mg/L, T(max) = 23.3 min), suggesting GHB is distributed into erythrocytes. All 12 volunteers had GHB concentrations of less than 5 mg/L in both whole blood and serum after 3 h. Results verify the rapid elimination of GHB and the limited retrospective power of a concentration-based approach to prove GHB administration in blood and urine and confirm that, in DFSA cases, samples should be collected as soon as possible.

Value of Follow-up Examinations of Children and Adolescents Evaluated for Sexual Abuse and Assault

The purpose of this study was to determine whether follow-up examinations of suspected victims of child sexual abuse influence medical diagnosis or treatment. A retrospective chart review of patients with initial and follow-up examinations (examinations 1 and 2, respectively) over a 5-year study period was conducted. Patient and abuse characteristics, interval between examinations and abuse, and examiner experience levels were collected; examination findings and test results for sexually transmitted infections (STIs) were compared for examinations 1 and 2. Among 727 patients, examination 2 resulted in a change in interpretation of trauma likelihood in 129 (17.7%) patients and identified STIs in 47 (6.5%) patients. Changes in trauma likelihood and detection of additional STIs during follow-up examinations were more likely in adolescent, female, and sexually active patients and those with a history of genital-genital contact, unknown examination 1 findings, or drug-facilitated sexual assault. Although examination 2 was less likely to affect the interpretation of trauma likelihood and STIs in preadolescent patients, a change in interpretation of trauma likelihood was noted for 49 (15.5%) of these patients, and 16 (5.1%) were diagnosed with a new STI on examination 2. The level of clinician experience during examination 1 did affect the likelihood of changes in examination findings during examination 2. Follow-up examinations by specialists affected the interpretation of trauma and detection of STIs in ∼23% of pediatric patients undergoing sexual abuse assessments.

The Problem of Untested Sexual Assault Kits

Victims of sexual assault are often advised to seek postassault medical care to have a forensic exam, which includes evidence collection (termed a sexual assault kit [SAK]). After the exam, law enforcement personnel are supposed to submit the SAK to a crime laboratory for analysis. However, recent media reports suggest that in many communities throughout the United States, thousands of SAKs are left untested. Few studies have examined the rate at which law enforcement submits SAKs to crime labs or the factors that may predict them to do so. Thus, the purpose of this exploratory study is twofold: (a) to examine the percentage of SAKs law enforcement submits to crime labs in cases in which a sexual assault nurse examiner (SANE) performed the exam with adult victims and (b) to explore whether assault and law enforcement characteristics predict whether SAKs are submitted to a crime lab. This study found that only 58.6% of the SAKs were submitted to the crime lab within a large Midwestern county. Using binary logistic regression, this study found that kits were significantly as likely to be submitted when there were documented physical (nonanogenital) injuries compared with kits that did not have documented physical injuries. In addition, kits that were handled by a law enforcement agency that had a high level of engagement with the SANE program were significantly as likely to be submitted as law enforcement agencies with a low or medium level of engagement. Kits were significantly less likely to be submitted when victims cleaned themselves after the sexual assault (e.g., bathing). No association was found between kit submission and the victim-offender relationship, suspected drug-facilitated sexual assault, anogenital injury, and when the victim consumed alcohol or drugs before the assault. This article concludes with a discussion of the implications for research and practice.

An Overview of Alcohol Testing and Interpretation in the 21st Century

Ethanol analysis is the most commonly carried out drug testing in a forensic toxicology laboratory. Determination of blood alcohol concentration (BAC) is needed in a multitude of situations, including in postmortem analysis, driving under the influence (DUI) and drug-facilitated sexual assault (DFSA) cases, workplace drug monitoring, and probation investigations. These analyses are carried out by direct measurement of ethanol concentrations as well as of metabolic by-products, such as ethyl glucuronide (EtG) and ethyl sulfate (EtS). This review article will discuss pharmacokinetics, including absorption, distribution, and elimination of ethanol, methods for the detection of ethanol, the effect of ethanol on human performance, the role of alcohol in injuries and fatalities, and information regarding the interactions that may occur between alcohol and other drugs. Finally, an explanation will be given on how to interpret alcohol levels as well as the extrapolation and calculation of blood alcohol levels at times prior to sample collection.