A combined toxicokinetic and metabolic approach to investigate deschloro-N-ethylketamine exposure in a multidrug user.

The use of new psychoactive substances derived from ketamine is rarely reported in France. A chronic GHB, 3-MMC, and methoxetamine consumer presented a loss of consciousness in a chemsex context and was referred to the intensive care unit with a rapid and favorable outcome. To investigate the chemicals responsible for the intoxication, a comprehensive analysis was conducted on the ten plasma samples collected over a 29.5-hour period, urine obtained upon admission, a 2-cm hair strand sample, and a seized crystal. These analyses were performed using liquid chromatography hyphenated to high resolution tandem mass spectrometry operating in targeted and untargeted modes. Additionally, analyses using gas chromatography coupled to mass spectrometry and nuclear magnetic resonance were conducted to probe the composition of the seized crystal. The molecular network-based approach was employed for data processing in non-targeted analyses. It allowed to confirm a multidrug exposure encompassing GHB, methyl-(aminopropyl)benzofuran (MAPB), (aminopropyl)benzofuran (APB), methylmethcathinone, chloromethcathinone, and a new psychoactive substance belonging to the arylcyclohexylamine family namely deschloro-N-ethyl-ketamine (O-PCE). Molecular network analysis facilitated the annotation of 27 O-PCE metabolites, including phase II compounds not previously reported. Plasma kinetics of O-PCE allowed the estimation of the elimination half-life of ∼5 hours. Kinetics of O-PCE metabolites was additionally characterized, possibly useful as surrogate biomarkers of consumption. We also observed marked alterations in lipid metabolism related to poly consumption of drugs. In conclusion, this case report provides a comprehensive analysis of exposure to O-PCE in a multidrug user including kinetic and metabolism data in human.

The interest of using vitreous humor for γ-hydroxybutyrate (GHB) quantification in related fatalities: Stability evaluation, case report and literature review.

Analysis and interpretation of the findings for γ-hydroxybutyrate (GHB) in related fatalities remains problematic. Indeed, GHB is a naturally occurring compound present in both the mammalian central nervous system and peripheral tissue. Moreover, a postmortem increase in endogenous GHB concentration has been observed, especially in blood. Facing this issue, the use of an alternative matrix such as vitreous humor (VH) can thus be particularly interesting for GHB testing and quantification. VH is considered to be less prone to postmortem redistribution, is easy to collect, and has relatively few interfering compounds for the analytical process. In this context, the authors report the case of a GHB-related fatality involving 22-year-old male. In this case, GHB femoral blood (FB) (790 mg/L) and vitreous (750 mg/L) concentrations appeared similar with a FB to VH (FB/VH) ratio of 1.05. In addition, other similar cases with both GHB blood and vitreous concentrations were reviewed. Five cases were identified. The blood to VH ratios ranging from 0.13 to 2.58. Finally, GHB stability was documented in postmortem blood and VH, in order to address the reliability of VH as an alternative matrix for GHB quantitation at postmortem. GHB appeared relatively stable in postmortem blood specimens (at 50 mg/L) over a period of 28 days when stored at +4 °C or -20 °C. The same results were observed in VH specimens.

Acute Sodium Oxybate Intoxication: A Case Report and Review of the Literature.

PURPOSE: Despite a better safety profile than illicit γ-hydroxybutyric acid (GHB) and other GHB analogs, sodium oxybate continues to raise serious concerns regarding clinical safety. In this study, the authors report the case of near-fatal intoxication involving sodium oxybate-alcohol combination in a 40-year-old woman. In addition, a review of the literature on published cases of intoxication involving this pharmaceutical form of GHB was conducted. A 40-year-old woman was admitted to the intensive care unit in a coma after voluntary ingestion of 18 g of sodium oxybate and alcohol. METHODS: The GHB plasma concentration was quantified to be 146 mg/L using liquid chromatography coupled with tandem mass spectrometry. An English literature search was performed using PubMed without any limiting period to identify all available scientific publications involving cases of sodium oxybate intoxication. RESULTS: Six cases were identified. Five involved fatal intoxication cases, with GHB postmortem blood concentrations ranging from 11.5 to 3500 mg/L. One involved a nonfatal intoxication case with a GHB serum concentration of 569 mg/L 7 hours postingestion. CONCLUSIONS: In the present case, the estimated elimination half-life was 154 minutes. The risk of acute poisoning seems to be high considering the pharmacokinetic properties of sodium oxybate. Physicians and toxicologists must take such properties into account.

Detection of Exogenous γ-Hydroxybutyric Acid in Rat Blood Exosomes.

OBJECTIVES: To find a method to distinguish exogenous gamma-hydroxybutyrate (GHB) from endogenous GHB by establishing ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) based on exosome for quantitative detection of GHB in the rat blood. METHODS: Adult male SD rats were divided into 1 h, 5 h, 10 h administration group and control group. After 1 h, 5 h and 10 h of single precursor of GHB gamma-butyrolactone (GBL) intraperitoneal injection in administration groups, 5 mL blood was collected from the abdominal aorta. Meanwhile, the control group was given a same dose of normal saline, and 5 mL blood was collected at 1 h. Among the 5 mL blood, 0.5 mL was directly detected by HPLC-MS after pretreatment, and exosomes were extracted from the remaining blood by differential centrifugation and detected. RESULTS: The concentration of GHB in the control group was (87.36±33.48) ng/mL, and the concentration with administration at 1 h, 5 h and 10 h was (110 400.00±1 766.35) ng/mL, (1 479.00±687.01) ng/mL and (133.60±12.17) ng/mL, respectively. The results of exosome detection showed that no peak GHB signal was detected in the control group and the 10 h administration group, and the concentrations of GHB at 1 h and 5 h administration groups were (91.47±33.44) ng/mL and (49.43±7.05) ng/mL, respectively. CONCLUSIONS: GHB was detected in blood exosome by UPLC-MS, which indicated that exogenous GHB could be detected in plasma exosomes, while endogenous GHB could not be detected, suggesting that this method may be used as a basis to determine whether there is exogenous drug intake.

Smartphone-based colorimetric determination of gamma-butyrolactone and gamma-hydroxybutyrate in alcoholic beverage samples.

Gamma-hydroxybutyrate (GBH) is a popular recreational drug. Its strong sedative and amnesic effects have led to drug-facilitated sexual assaults, poisonings, overdose, and death. As a result, legislation has restricted its availability leading to GHB, consumers switching to its pro-drug, gamma-butyrolactone (GBL). Consequently, there is a growing need for methods capable of their determination in complex samples such as beverages. Previous studies have shown the possibility to colorimetrically qualitatively determine both GBH and GBL by the formation of the lactone and its reaction with hydroxylamine and ferric chloride to give a purple-colored complex. In this present investigation, we have shown the possibility of using this approach to both quantify GBL and GHB using both UV/Vis spectrometry and by the application of the camera of a smartphone to record images of the purple color developed. Via subsequent use of a downloadable free App, to extract the numerical values of the Red, Green, and Blue (RGB) color components, it was shown possible to construct a calibration curve and to quantitatively determine the concentration of the drugs present in fortified alcoholic beverage samples. It was found that by simple mathematical normalization of the RGB values the effects of camera distance and elimination could be readily overcome. Using the smartphone approach, GBL determinations on a sample of lager beer gave a mean recovery of 103% (%CV = 0.70%, n = 5) at a concentration of 0.56 mg/ml indicating the method holds promise for the determination of GBL and GHB in such samples.

Detection of Exogenous γ-Hydroxybutyric Acid in Rat Blood Exosomes / 法医学杂志

OBJECTIVES@#To find a method to distinguish exogenous gamma-hydroxybutyrate (GHB) from endogenous GHB by establishing ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) based on exosome for quantitative detection of GHB in the rat blood.@*METHODS@#Adult male SD rats were divided into 1 h, 5 h, 10 h administration group and control group. After 1 h, 5 h and 10 h of single precursor of GHB gamma-butyrolactone (GBL) intraperitoneal injection in administration groups, 5 mL blood was collected from the abdominal aorta. Meanwhile, the control group was given a same dose of normal saline, and 5 mL blood was collected at 1 h. Among the 5 mL blood, 0.5 mL was directly detected by HPLC-MS after pretreatment, and exosomes were extracted from the remaining blood by differential centrifugation and detected.@*RESULTS@#The concentration of GHB in the control group was (87.36±33.48) ng/mL, and the concentration with administration at 1 h, 5 h and 10 h was (110 400.00±1 766.35) ng/mL, (1 479.00±687.01) ng/mL and (133.60±12.17) ng/mL, respectively. The results of exosome detection showed that no peak GHB signal was detected in the control group and the 10 h administration group, and the concentrations of GHB at 1 h and 5 h administration groups were (91.47±33.44) ng/mL and (49.43±7.05) ng/mL, respectively.@*CONCLUSIONS@#GHB was detected in blood exosome by UPLC-MS, which indicated that exogenous GHB could be detected in plasma exosomes, while endogenous GHB could not be detected, suggesting that this method may be used as a basis to determine whether there is exogenous drug intake.

Levels of GHB in hair after regular application.

Gamma hydroxybutyrate (GHB) is a central nervous system depressant that is an approved drug for the treatment of narcolepsy with cataplexy and other syndromes. Due to its dose dependent stimulating, relaxing or sedative effects, illicit abuses include recreational use by young people and cases of drug-facilitated crime (DFC). Since GHB is also produced endogenously, for forensic questions, it is important to be able to differentiate between endogenous GHB and elevated levels due to additional intake. In this study, we measured GHB concentrations in hair of patients with narcolepsy receiving daily GHB treatment. The results were compared to endogenous concentrations and concentrations after chronic intake presented in several former studies. The aim of this study was to investigate whether a regular intake of a known dosage of GHB leads to elevated levels of GHB concentration in hair. We collected hair samples of 19 patients (14 female, 5 male) with narcolepsy under regular GHB treatment and examined the hair samples segmentally by digestion of the hair followed by liquid-liquid extraction and analysis using a Shimadzu LC20 UFLC system coupled with an AB Sciex API 4000 Qtrap tandem mass spectrometer. All volunteers received daily treatment with different doses of sodium oxybate (sodium salt of GHB) ranging between 3 and 9g per night. The observed mean value of GHB concentration in hair was 2.69ng GHB per mg hair for the 5 male participants, 1.56ng/mg for the 14 female participants giving an overall mean value of 1.86ng/mg for all participants. Our results showed no correlation between the daily dose or the duration intake of GHB and the measured concentration of GHB in hair. Although we did find a significant (p<0.01) difference between published endogenous levels of GHB in hair and GHB levels in hair of patients with regular daily GHB intake, the forensic relevance however is disputable. We hypothesise this narrow margin or even overlap to be the reason why analytical results from hair analysis in some cases fail to provide a reliable prove of a single exposition.

GHB related acids are useful in routine casework of suspected GHB intoxication cases.

GHB related acids (3,4-dihydroxy butyric acid, 2,4-dihydroxy butyric acid and glycolic acid) are produced through oxidative GHB metabolism. These analytes could be potential biomarkers to ensure the diagnosis of a GHB intoxication and even prolong the detection window. Within this study, forensic routine cases were measured to consider the potential of additional gas chromatographic mass spectrometric analysis on these acids. 17 GHB positive real cases (10 serum samples and 7 urine samples) and 40 cases with suspicion of drugging in DFC cases and negative GHB results (21 serum samples and 19 urine samples) were evaluated. Increased GHB related acid concentrations were detected in all serum and most urine samples positive on GHB. In some GHB negative cases, especially in serum samples, concentrations of GHB related acids gave hints that GHB actually was taken. We recommend to use the following cut-offs for a more reliable interpretation of potential GHB intoxication cases: 3,4-OH-BA:>3 mg/L in serum and>50 mg/L in urine; 2,4-OH-BA:>2 mg/L in serum and>25 mg/L in urine; GA:>5 mg/L in serum and>400 mg/L in urine.

Chemsex/slamsex-related intoxications: A case report involving gamma-hydroxybutyrate (GHB) and 3-methylmethcathinone (3-MMC) and a review of the literature.

Chemsex and slamsex represent a serious public health concern that has to be considered by both clinical and forensic toxicologists. Indeed, such practices appear to carry a significant degree of risk, including acute intoxication. Here we report the case of the intoxication of a 31-year-old male involving 3-methylmethcathinone (3-MMC) and gamma-hydroxybutyrate (GHB) during a slamsex session. In addition, we conducted a review of further cases. The 31-year-old man was admitted to the emergency department for severe impaired consciousness following the administration of psychoactive substances during a chemsex party. The detection and determination of 3-MMC and GHB concentrations were achieved using liquid chromatography-tandem mass spectrometry. 3-MMC and GHB blood concentrations were 177 ng/mL and 131 mg/L, respectively. Further, an English and French exhaustive literature search was performed using several different electronic databases without any limiting period in order to identify all published case reports detailing chemsex/slamsex-related (fatal and nonfatal) intoxications. Nine publications detailing chemsex/slamsex-related intoxication cases have been published (between 2016 and 2020). These articles reported an overall of 13 cases, all involving men with a mean age of 39.1±9.8 years. The outcome was fatal in only 6 cases. 4-MEC and GHB were the two predominant drugs identified. However, given the rapid emergence of novel NPSs in the global market as well as the ease with which they can be accessed through the Internet, toxicological laboratories have to be ready to face new patterns of intoxications resulting from chemsex/slamsex.

GHB concentration in a related post-mortem case.

Gamma-hydroxybutyrate (GHB) is a central nervous system depressant, primarily used as a recreational drug of abuse and as a therapeutic substance both in U.S.A. and Europe for the treatment of narcolepsy with cataplexy in adult patients and as adjuvant in the control of alcohol withdrawal syndrome. Several cases of GHB related deaths have been reported in the literature and GHB was found alone or in association to other drugs of abuse. However, only few biological matrices are often analyzed, therefore data on GHB distribution are lacking. Here we report a case involving a 45-year-old man, who was found dead in his bedroom.

The assessment and management of gamma hydroxybutyrate use in general practice.

BACKGROUND: Gamma hydroxybutyrate (GHB) is an illicit drug commonly used in music festival, party and 'chemsex' settings. Most people who use GHB do so occasionally, without dependent use or withdrawal symptoms. However, a minority of users experience harms including unconsciousness and respiratory collapse in overdose. Adverse interactions can also occur when GHB is used with other drugs (eg methamphetamine), necessitating assessment, management or onward referral by general practitioners. OBJECTIVE: This article describes the use of GHB, with a contemporary update on principles of assessment and management in general practice, brief intervention and harm-minimisation strategies, and indicators for referral to a specialist in dependent use. DISCUSSION: The assessment and management of individuals with GHB-related harms in general practice is supported by an awareness of the context of use, familiarity with targeted harm-minimisation advice and cognisance of markers of risk indicating onward referral to specialist addiction services when appropriate.

Interpreting γ-hydroxybutyrate concentrations for clinical and forensic purposes.

INTRODUCTION: γ-Hydroxybutyric acid is an endogenous substance, a therapeutic agent, and a recreational drug of abuse. This psychoactive substance acts as a depressant of the central nervous system and is commonly encountered in clinical and forensic practice, including impaired drivers, poisoned patients, and drug-related intoxication deaths. OBJECTIVE: The aim of this review is to assist clinical and forensic practitioners with the interpretation of γ-hydroxybutyric acid concentrations in blood, urine, and alternative biological specimens from living and deceased persons. METHODS: The information sources used to prepare this review were PubMed, Scopus, and Web-of-Science. These databases were searched using keywords γ-hydroxybutyrate (GHB), blood, urine, alternative specimens, non-conventional biological matrices, saliva, oral fluid, sweat, hair, vitreous humor (VH), brain, cerebrospinal fluid (CSF), dried blood spots (DBS), breast milk, and various combinations thereof. The resulting 4228 references were screened to exclude duplicates, which left 1980 articles for further consideration. These publications were carefully evaluated by taking into account the main aims of the review and 143 scientific papers were considered relevant. Analytical methods: The analytical methods used to determine γ-hydroxybutyric acid in blood and other biological specimens make use of gas- or liquid-chromatography coupled to mass spectrometry. These hyphenated techniques are accurate, precise, and specific for their intended purposes and the lower limit of quantitation in blood and other specimens is 0.5 mg/L or less. Human pharmacokinetics: GHB is rapidly absorbed from the gut and distributes into the total body water compartment. Only a small fraction of the dose (1-2%) is excreted unchanged in the urine. The plasma elimination half-life of γ-hydroxybutyric acid is short, being only about 0.5-0.9 h, which requires timely sampling of blood and other biological specimens for clinical and forensic analysis. Endogenous concentrations of GHB in blood: GHB is both an endogenous metabolite and a drug of abuse, which complicates interpretation of the laboratory results of analysis. Moreover, the concentrations of GHB in blood and other specimens tend to increase after sampling, especially in autopsy cases. This requires the use of practical "cut-off" concentrations to avoid reporting false positive results. These cut-offs are different for different biological specimen types. Concentrations of GHB in clinical and forensic practice: As a recreational drug GHB is predominantly used by young males (94%) with a mean age of 27.1 years. The mean (median) and range of concentrations in blood from apprehended drivers was 90 mg/L (82 mg/L) and 8-600 mg/L, respectively. The concentration distributions in blood taken from living and deceased persons overlapped, although the mean (median) and range of concentrations were higher in intoxication deaths; 640 mg/L (280 mg/L) and 30-9200 mg/L, respectively. Analysis of GHB in alternative specimens: All biological fluids and tissue containing water are suitable for the analysis of GHB. Examples of alternative specimens discussed in this review are CSF, saliva, hair strands, breast milk, DBS, VH, and brain tissue. CONCLUSIONS: Body fluids for the analysis of GHB must be obtained as quickly as possible after a poisoned patient is admitted to hospital or after a person is arrested for a drug-related crime to enhance chances of detecting the drug. The sampling of urine lengthens the window of detection by 3-4 h compared with blood samples, but with longer delays between last intake of GHB and obtaining specimens, hair strands, and/or nails might be the only option. In postmortem toxicology, the concentrations of drugs tend to be more stable in bladder urine, VH, and CSF compared with blood, because these sampling sites are protected from the spread of bacteria from the gut. Accordingly, the relationship between blood and urine concentrations of GHB furnishes useful information when drug intoxication deaths are investigated.

Toxicological findings in 1000 cases of suspected drug facilitated sexual assault in the United States.

The purpose of this study was to identify the extent and types of drugs found in alleged drug facilitated sexual assaults (DFSA) in 37 states and 1 territory of the United States. In total, 1000 cases were reviewed. Between the cases that gender was provided (613), most of the victims (91.68%) were woman, mean age of 26.8 years old. Blood and/or urine samples were tested. Twenty-one point six percent of the cases were negative for intoxicating substances. A hundred and one different substances were detected. Overall, ethanol was the most prevalent substance, detected in 30.9% of the cases (309 cases), followed by cannabinoids (THC/THCCOOH/11-OH-THC) (28.8% of cases), amphetamine/methamphetamine (16.5% of cases), cocaine/metabolites (10.4% of cases), and clonazepam/metabolite (7.6% of cases). The mean, median and range concentrations of ethanol in blood (n = 309) were 98.6 mg/dL, 82.0 mg/dL and 9.2-366 mg/dL, respectively. Ethanol and cannabinoids were the most frequent combination found. The absence of alcohol and drugs in some cases may represent delay in collecting samples.

Gammahydroxybutyrate in hair of non-GHB and repeated GHB users: A new and optimized method.

Gamma-hydroxybutyric acid (GHB) is a short-chain fatty acid used recreationally as a drug of abuse due its strong suppressive effect on the central nervous system. The detection window of GHB in blood and urine is very narrow (t1/2=30min) but can be substantially prolonged using alternative matrices such as hair. We here present a newly developed and limited validated method with a solid phase extraction (SPE) using GC-MS/MS to determine concentrations of GHB in hair samples. The soft extraction technique (water and 90min ultrasonic bath) preserves GHB with a high yield and clean extracts. In addition, endogenous GHB can be detected in hair of non-GHB users. However, little is known about GHB concentrations in hair of abstinent, frequent and chronic GHB users. Therefore, we present data from hair samples of healthy volunteers to evaluate the proposed endogenous GHB ranges, and from GHB-dependent patients to address GHB concentrations in hair with GHB intake. In 20 non-GHB users, a mean endogenous concentration of 1.1±0.6ng/mg hair (range of 0.3-2ng/mg) was found. In GHB-dependent patients, concentrations between 6.3-239.6ng/mg hair were found, with no correlation between concentrations in hair and dose of GHB intake. In summary, we present a new and limited validated method, adequately sensitive for the detection of GHB in hair, as well as first-time measurements of GHB concentrations in dependent patients in order to better understand the relationship between the frequency of use/dose and concentrations observed in hair samples.

Multiple analyte adduct formation in liquid chromatography-tandem mass spectrometry - Advantages and limitations in the analysis of biologically-related samples.

Multiple analyte adduct formation was examined and discussed in the context of reproducible signal detection in liquid chromatography-tandem mass spectrometry applied in the analysis of biologically-related samples. Appropriate infusion solutions were prepared in H2O/methanol (3/97, v/v) with 1 mM sodium acetate and 10 mM acetic acid. An API 4000 QTrap tandem mass spectrometer was used for experiments performed in the negative scan mode (-Q1 MS) and the negative enhanced product ion mode (-EPI). γ­Hydroxybutyrate and its deuterated form were used as model compounds to highlight both the complexity of adduct formation in popular mobile phases used and the effective signal compensation by the application of isotope-labelled analytes as internal standards.

Hair testing of GHB: an everlasting issue in forensic toxicology.

BACKGROUND: In this paper, the authors present a critical review of different studies regarding hair testing of endogenous γ-hydroxybutyrate (GHB), concentrations in chronic users, and values measured after a single GHB exposure in drug facilitated sexual assault (DFSA) cases together with the role of a recently identified GHB metabolite, GHB-glucuronide. CONTENT: The following databases (up to March 2017) PubMed, Scopus and Web of Science were used, searching the following key words: γ-hydroxybutyrate, GHB, GHB glucuronide, hair. The main key words "GHB" and "γ-hydroxybutyrate" were searched singularly and then associated individually to each of the other keywords. SUMMARY: Of the 2304 sources found, only 20 were considered appropriate for the purpose of this paper. Summing up all the studies investigating endogenous GHB concentration in hair, a very broad concentration range from 0 to 12 ng/mg was found. In order to detect a single GHB dose in hair it is necessary to commonly wait 1 month for collecting hair and a segmental analysis of 3 or 5 mm fragments and the calculation of a ratio between the targeted segment and the others represent a reliable method to detect a single GHB intake considering that the ratios presently proposed vary from 3 and 10. The only two studies so far performed, investigating GHB-Glucuronide in hair, show that the latter does not seem to provide any diagnostic information regarding GHB exposure. OUTLOOK: A practical operative protocol is proposed to be applied in all suspected cases of GHB-facilitated sexual assault (GHB-FSA).

Gamma-hydroxybutyrate (GHB), an unusual cause of high anion gap metabolic acidosis.

The causes of high anion gap metabolic acidosis (HAGMA) are well described in the literature. However, sometimes more frequent causes of HAGMA cannot explain its occurrence.In the case of HAGMA and severe neurological depression in the absence of other causes of HAGMA, clinicians should consider an intoxication with gamma-hydroxybutyrate (GHB) as a possible cause.GHB is endogenous to the mammalian central nervous system (CNS). Synthetic GHB was initially used as an anesthetic but is now only licensed for medical use in a limited number of indications such as the treatment of narcolepsy. Because of its euphoric effects, it became popular for recreational use under the street names: Liquid Ecstasy, Georgia Home Boy, and Liquid G.We describe the clinical case of a patient who suffered from severe neurological depression and HAGMA.

Fatal Overdose of Gamma-hydroxybutyrate Acid After Ingestion of 1,4-Butanediol.

We report a case of fatal intoxication from 1,4-butanediol (1,4-BD), which was ingested by a young and "naïve" gamma-hydroxybutyrate (GHB) consumer during a party with the co-ingestion of alcohol, cannabis, and methylene-dioxy-methamphetamine. The following drug concentrations were found using gas chromatography coupled with mass spectrometry on autopsy samples and on a cup and a glass found at the scene: 20,350 mg/L (bottle) for 1,4-BD; 1020 mg/L (femoral blood), 3380 mg/L (cardiac blood), 47,280 mg/L (gastric content), and 570 mg/L (vitreous humor) for GHB. The concentration of GHB is difficult to interpret in forensic cases due to the possibility of an endogenous production of GHB. The variable tolerance of the user may also modify the peri- and postmortem GHB concentrations. This case underscores the need to have many different sources of toxicology samples analyzed to avoid the hypothesis of endogenous production of GHB.

Determination of GHB and GHB-ß-O-glucuronide in hair of three narcoleptic patients-Comparison between single and chronic GHB exposure.

Gamma-hydroxybutyric acid (GHB) can be used as a knock-out drug in drug facilitated crime (DFC). Due to its rapid metabolism and resulting narrow detection window, uncovering GHB use in DFC still constitutes a problem. In this experiment we determined the GHB and GHB-ß-O-glucuronide (GHB-Gluc) concentrations in hair samples after single and chronic GHB exposures. Hair samples of three narcoleptic patients therapeutically taking sodium oxybate (GHB-sodium-salt) were collected. Patients 1 (P1) and 2 (P2) took the medication for nine and six years, respectively. P1 took daily the pharmaceutical Xyrem® in a total dose of 5.78g GHB at bed time (2.89g) and four hours (2.89g) later. P2 took a dose of 3.10g GHB at bed time and an additional dose of 2.68g GHB four hours later. Patient 3 (P3) was newly diagnosed with narcolepsy and started his therapy with oral dose of 6g (divided in three portions of 2g GHB) within 24h. The hair samples were extracted both with and without forerunning washing steps. GHB and GHB-Gluc were determined by a published ultra-high performance liquid chromatography-tandem mass spectrometry method using GHB-d6 and GHB-Gluc-d4 as internal standards. GHB and GHB-Gluc concentrations in unwashed hair samples of P1 and P2 were determined in a range of 0.56-1.30ng/mg and <0.48-0.85ng/mg, respectively. In washed hair samples of P1 and P2 the concentrations were in a range of <0.32-0.68ng/mg and <0.48-1.20ng/mg for GHB and GHB-Gluc, respectively. The determined concentrations were within the published endogenous range. The confirmed results showed that the washing procedure before extraction causes a minor decrease of GHB concentrations in hair (difference: <1ng/mg). The investigations showed that a single GHB exposure might not be determined by hair analysis of GHB and GHB-Gluc. The chronical intake of therapeutic sodium oxybate with doses up to 7g per night was also not confirmed by hair analysis maybe due to hair treatments. Therefore, GHB hair analysis should be assessed critically and determined negative results could not exclude GHB exposures.

GHB-involved crimes among intoxicated patients.

INTRODUCTION: In recent years, the involvement of GHB in drug facilitated sexual assaults has been one of the most frequently studied aspects of GHB in both clinical and non-clinical settings. GHB-involved acquisitory crimes, however, can be mentioned as understudied research topics, as well as the poisoning severity properties of GHB. MEASURES: The medical reports of Péterfy Sándor Street Hospital Clinic and Casualty Centre's 408 GHB-intoxication cases (352 patients) were reviewed and registered. Analyzed data consisted of epicrisis, serum and urine concentration of various substances (including GHB), scores of Glasgow Coma Scale and Poisoning Severity Score. RESULTS: Majority of the patients were males, in their twenties. GHB was detected in 34.1% and it was solely consumed in 27.7% of all the cases. Ethanol was found to be the most frequently co-ingested substance. A higher rate of severe poisonings was observed among males. We found significant difference in the frequency of enduring sexual assaults and acquisitory crimes between intentional and unintentional GHB intake cases. Among unintentional GHB intake cases, 6.5% endured GHB-involved sexual assaults, whereas 21.7% endured an acquisitory crime. Among recurrent GHB intoxication cases generated by the same patients, voluntary and sole GHB consumptions were more frequently observed, however, enduring any crime was less characteristic. DISCUSSION: Our results regarding demographic and substance use characteristics and the frequency of GHB-facilitated sexual assaults are in line with former findings. Enduring acquisitory crimes due to unintentional GHB intake was found to be more inherent than enduring sexual assaults. Authors emphasise that the victims of these acquisitory crimes were typically males. CONCLUSION: GHB's role in drug facilitated acquisitory crimes seems to be significant, although the decrease in GHB's popularity is observed among intoxicated patients as well. The need for further research on GHB's impact on cognitive impairment and on sexual correlates of intentional GHB use is addressed by the authors.