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The death of a 72-year-old woman with respiratory debilitation due to bronchogenic carcinoma is described. She overdosed herself with probably 200 to 350 mg of zopiclone. Zopiclone, quantitated by HPLC in femoral postmortem blood, was... more
The death of a 72-year-old woman with respiratory debilitation due to bronchogenic carcinoma is described. She overdosed herself with probably 200 to 350 mg of zopiclone. Zopiclone, quantitated by HPLC in femoral postmortem blood, was found to be 1.9 mg/L (4.8 micromol/L). This level is higher than many other zopiclone fatalities reported. We report a case where only zopiclone was detected.
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Methiopropamine (MPA; 1-(thiophen-2-yl)-2-methylaminopropane) belongs to the new psychoactive substances (NPS) which have emerged on the drug marked over the last years. MPA appeared in 2011 and is an analogue of methamphetamine, sold as... more
Methiopropamine (MPA; 1-(thiophen-2-yl)-2-methylaminopropane) belongs to the new psychoactive substances (NPS) which have emerged on the drug marked over the last years. MPA appeared in 2011 and is an analogue of methamphetamine, sold as e.g. "Slush Eric" and "Blow". It is reported to have similar effects as methamphetamine, but the toxicity in humans is not known. Three fatal cases involving MPA have been reported. One analytical confirmed intoxication case has been published, and this supports the symptoms described by the users. The prevalence of recreational use of MPA is unknown, and no studies have reported the prevalence in driving under the influence of drug (DUID) cases. We have investigated the frequency of MPA in DUID cases received at our institute during a 12 week period, and report the analytical method using an UPLC-MS/MS for quantification of MPA in whole blood. The analytical findings were compared to the results from a clinical test of impairmen...
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Quantitative determination of anti-epileptic drug concentrations is of great importance in forensic toxicology cases. Although the drugs are not usually abused, they are important post-mortem cases where the question of both lack of... more
Quantitative determination of anti-epileptic drug concentrations is of great importance in forensic toxicology cases. Although the drugs are not usually abused, they are important post-mortem cases where the question of both lack of compliance and accidental or deliberate poisoning might be raised. In addition these drugs can be relevant for driving under the influence cases. A reversed phase ultra-performance liquid chromatography-tandem mass spectrometry method has been developed for the quantitative analysis of the anti-epileptic compounds carbamazepine, carbamazepine-10,11-epoxide, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, 10-OH-carbazepine, phenobarbital, phenytoin, pregabalin, and topiramate in whole blood, using 0.1 mL sample volume with methaqualone as internal standard. Sample preparation was a simple protein precipitation with acetonitrile and methanol. The diluted supernatant was directly injected into the chromatographic system. Separation was performed on a...
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The long-term stability of benzodiazepines, opioids, central stimulants and medicinal drugs in authentic postmortem blood samples was studied. All together, 73 samples were reanalyzed after storage at -20°C for 16-18 years. At reanalysis... more
The long-term stability of benzodiazepines, opioids, central stimulants and medicinal drugs in authentic postmortem blood samples was studied. All together, 73 samples were reanalyzed after storage at -20°C for 16-18 years. At reanalysis samples containing diazepam, nordiazepam and flunitrazepam demonstrated only small changes during long-term storage when mean and median drug concentrations were compared, while clonazepam concentrations tended to decrease. Samples containing amphetamine, morphine, codeine and 'acidic' medicinal drugs as paracetamol and meprobamate also showed small changes over 16-18 years in mean and median drug concentrations at a group level. For many drugs, however, single samples could demonstrate marked concentration changes, both increases and decreases during storage. For 'alkaline' medicinal drugs, concentration losses were observed in most cases.
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Phenazone is a non-opioid analgesic used to treat acute mild to moderate pain, and is considered to be a safe drug. It is most often sold as a nonprescription/over-the-counter drug. Very few fatalities due to phenazone overdoses are... more
Phenazone is a non-opioid analgesic used to treat acute mild to moderate pain, and is considered to be a safe drug. It is most often sold as a nonprescription/over-the-counter drug. Very few fatalities due to phenazone overdoses are reported in the literature. We present a case where a man in his early sixties was found dead in his home in the bottom of a staircase, the scene suggesting that death might have been caused by blunt force injury. However, in spite of the apparently dramatic scene, the gross findings at autopsy did not reveal lethal injuries. Whole blood from the femoral vein was collected during autopsy and screened for drugs of abuse and medicinal drugs. The only toxicological findings were a very high concentration of phenazone (280mg/L) and a high therapeutic concentration of caffeine (34mg/L). An UPLC-MS/MS method was used for quantification of the drugs.
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The aim of this study is to investigate the concentrations of ethyl glucuronide (EtG) in oral fluid and both EtG and ethyl sulfate (EtS) in blood and urine following intense use of mouthwash and ingestion of nonalcoholic wine, which are... more
The aim of this study is to investigate the concentrations of ethyl glucuronide (EtG) in oral fluid and both EtG and ethyl sulfate (EtS) in blood and urine following intense use of mouthwash and ingestion of nonalcoholic wine, which are proven to contain 3 mg/L EtG, 1.5 mg/L EtS, and 0.2 g/L ethanol. Twelve subjects participated in a controlled experiment. All subjects ingesting nonalcoholic wine showed urine samples negative for EtG but positive for EtS (Cmax 2.15 mg/L). All four subjects using mouthwash were negative for EtG and EtS in urine. All samples of oral fluid were negative for EtG and all samples of blood were negative for EtG and EtS. This study showed that ingestion of EtG and EtS as components of nonalcoholic wine lead to detection of urine EtS only, suggesting superior bioavailability of orally ingested EtS compared to EtG. This possibility of false-positive EtS results in urine after ingestion of nonalcoholic wine is important to remember when using EtG and EtS as relapse markers for alcohol. Finally, the study showed that a positive EtG or EtS result after accidental alcohol exposure is unlikely in blood and oral fluid.
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The aim of this study was to investigate the concentrations of ethyl glucuronide (EtG) in oral fluid, blood, and urine after healthy volunteers drank two doses of ethanol, 0.5 (n = 11) and 1.0 g/kg (n = 10), after an overnight fast.... more
The aim of this study was to investigate the concentrations of ethyl glucuronide (EtG) in oral fluid, blood, and urine after healthy volunteers drank two doses of ethanol, 0.5 (n = 11) and 1.0 g/kg (n = 10), after an overnight fast. Samples of oral fluid, blood, and urine were collected before drinking started and at 1.5, 3.5, 5.5, 8.5, 11.5, and 24 h post-dosing. Following ingestion of low dose of ethanol, the Cmax for EtG was 0.36 mg/L (range 0.28-0.41 mg/L) in blood and 69.8 mg/L (range 47.1-96.5 mg/L) in urine. In oral fluid, the concentrations were < 1% of those in blood, and only three subjects exceeded the limit of quantification for EtG in oral fluid. After ingestion of the high dose of ethanol, the Cmax for EtG was 1.06 mg/L (range 0.8-1.22 mg/L) in blood, 159.9 mg/L (range 97.2-225.5 mg/L) in urine, and 0.032 mg/L (range 0.013-0.059 mg/L) in oral fluid. The median oral fluid/blood ratio was 0.029 (range 0.012-0.054) for EtG. The detection time for EtG was median 11.5 h (range 3.5-11.5 h) in oral fluid. According to this, the detection time for EtG in oral fluid is therefore only a few hours longer than for ethanol itself and represents limited additional value.
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In postmortem toxicology, it could be difficult to determine whether a positive blood ethanol concentration reflects antemortem ingestion or postmortem synthesis of alcohol. Measurement of the nonoxidative ethanol metabolite ethyl... more
In postmortem toxicology, it could be difficult to determine whether a positive blood ethanol concentration reflects antemortem ingestion or postmortem synthesis of alcohol. Measurement of the nonoxidative ethanol metabolite ethyl glucuronide (EtG) has been suggested as a marker of antemortem ingestion of alcohol, but EtG might degrade postmortem which could make interpretation difficult. So far, the published articles concern EtG only. Another nonoxidative metabolite, ethyl sulfate (EtS), which is more stable, has therefore been included in this study. We present a material of 36 deaths where postmortem formation of ethanol was suspected and where both EtG and EtS were measured in blood and urine to assist the interpretation. In 19 cases, EtG and EtS were positive in the body fluids analyzed. The median concentration of EtG and EtS in blood was 0.4 (range 0.1-23.2) and 0.9 mg/L (range 0.04-7.9), respectively. The median concentration of EtG and EtS in urine was 35.9 (range 1.0-182) and 8.5 mg/L (range 0.3-99), respectively. In another 16 cases, there was no trace of EtG or EtS in the specimens analyzed. In one case, there was inconsistency between the results of EtG and EtS; they were both positive in urine, while only EtS was positive in blood. This study showed that, out of 36 cases, antemortem ingestion of alcohol was very likely in 19 and unlikely in 16, according to EtG and EtS results. In the last case, the interpretation was more difficult. One possible explanation would be postmortem degradation of EtG in blood.
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There are previous publications showing the use of ethyl glucuronide (EtG), a non-oxidative metabolite of ethanol, as a marker of ante-mortem ingestion of alcohol in forensic autopsy cases. The problem of possible degradation or formation... more
There are previous publications showing the use of ethyl glucuronide (EtG), a non-oxidative metabolite of ethanol, as a marker of ante-mortem ingestion of alcohol in forensic autopsy cases. The problem of possible degradation or formation of EtG during putrefaction is however not well studied and the aim of this study was to investigate the possibility of false negative and false positive EtG results by an in vitro study. Further, we used the information from the in vitro study on real cases, to get an impression of the practical problem of degradation or formation of EtG. An in vitro study was carried out to study the concentrations of EtG in blood samples under controlled conditions during putrefaction. In addition, to illustrate the practical problem of degradation or formation of EtG, we used routine samples analysed for EtG in blood. Blood samples from forensic autopsies with ethanol detected but EtG not detected in blood, and therefore suspected post-mortem ethanol formation, were identified. Fifteen such cases had urine samples available, and these were analysed for EtG. We hypothesised that since concentrations are often higher in urine, there would still be traces of EtG left in this medium if post-mortem degradation was the reason for the negative result in blood. In this in vitro experiment, EtG was very unstable in blood samples at 30/40 degrees C without preservatives. On the other hand, EtG was stable with potassium fluoride at room temperature, and there was no formation of EtG either at 30 degrees C without preservatives, or at room temperature with potassium fluoride. Of the 15 routine cases where EtG in blood was negative, and the ethanol detected was assumed endogenous, six were positive for EtG in urine. In these cases, ethanol was probably ingested, and the negative EtG in blood may be a false negative result due to degradation during putrefaction. Analysis of EtG in blood is a helpful tool to determine in vivo ingestion of ethanol in post-mortem cases. A negative result, however, especially in heavily putrefied cases, must be interpreted with caution. Analysis of an additional medium would be valuable in these cases.
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information on the clinical effects associated with whole blood gamma-hydroxybutyrate (GHB) concentrations is sparse. We have investigated possible relationships between GHB blood concentrations and clinical effects in car drivers. in... more
information on the clinical effects associated with whole blood gamma-hydroxybutyrate (GHB) concentrations is sparse. We have investigated possible relationships between GHB blood concentrations and clinical effects in car drivers. in Norway, the police stop car drivers suspected of drug-driving. Medical doctors perform a clinical test of impairment (CTI) and blood samples are screened for drugs/medicines by immunological, enzymatic and chromatographic methods at the Division of Forensic Toxicology and Drug Abuse. GHB is a part of our extended drug-testing programme. GHB is standardly measured as GBL by gas chromatographic method. All the results were stored in a database. This database was searched between 2000 and 2007 for car drivers positive only for GHB, called GHB-drivers. A control group with a completely negative blood analysis, including GHB, called control-drivers, was included in the study. twenty-five car drivers had only GHB in their blood. The police reported that 78% showed unsafe driving behaviour and seven were involved in car accidents, without serious injury. A total of 61% of the drivers were found to be sleepy or in an even more reduced state of consciousness. The median GHB blood concentration was 1,262 (range 592-2,191) μmol/L, measured a median of 69 min after the police had stopped the driver from driving. The GHB blood concentration tended to increase with increasing impairment and reduced consciousness. Clinical findings were normal- to large-sized pupils (86%), impairment as the final conclusion (84%), impaired balance/nystagmus (62 and 54%, respectively), congested/shiny conjunctiva (67%), apathetic, aggressive or abnormal behaviour (65%), reduced short-term memory (67%), reduced/absent pupillar reaction to light (65%), heart rate ≤ 70 beats/min (56%), and some level of reduced consciousness (56%). In the control-drivers, 15.6% were found by the medical doctors to have reduced consciousness or impaired. the median GHB blood concentration of the 25 car drivers was high. Most drivers had clinical impairment that was not explainable by injuries, with depressive effects on the central nervous system and sympathomimetic effects on eyes. Effects on impairment and consciousness tended to be concentration-dependent. The number of drivers who were impaired or had reduced consciousness was highly increased in GHB-drivers compared to controls. Based on these results, we conclude that the GHB-drivers most probably drove in an unsafe manner due to impairment by GHB.
Research Interests: Police, Consciousness, Forensic Toxicology, Safety, Norway, and 5 moreHumans, Female, Male, Adult, and Biological markers
The centrally acting muscle relaxant carisoprodol has previously been shown to cause psychomotor impairment and to have a narrow therapeutic range. In Norway, carisoprodol was therefore reclassified to the highest scheduling level from 1... more
The centrally acting muscle relaxant carisoprodol has previously been shown to cause psychomotor impairment and to have a narrow therapeutic range. In Norway, carisoprodol was therefore reclassified to the highest scheduling level from 1 August 2007 and withdrawn from the market on 1 May 2008. The aim of this study was to examine to what extent this action resulted in reduced numbers of driving under the influence (DUI) cases and forensic autopsies concerning carisoprodol, as well as reduced numbers of contacts to the National Poisons Information Centre (NPIC) in Norway regarding carisoprodol. From 2004 to 2008, carisoprodol (and/or its metabolite meprobamate) was detected in a total of 1261 DUI cases, decreasing from 312 in 2004 to 47 in 2008. During the same period, carisoprodol was detected in 194 forensic autopsies, also here decreasing, from 53 cases in 2004 to 11 cases in 2008. The NPIC received 1180 contacts primarily concerning carisoprodol over this period, decreasing from 267 contacts in 2004 to 87 contacts in 2008. During the same period, the sales figures for carisoprodol decreased dramatically, and we observed a relation between the numbers of DUI cases, forensic autopsies and contacts to the NPIC concerning carisoprodol and the sales figures for the drug. This study showed that the rescheduling and withdrawal of carisoprodol from the Norwegian market had a positive effect on the prevalence of carisoprodol in impaired driving, deaths and contacts regarding intoxications. This, together with previous publications, indicates that the population reflected in our data uses regularly prescribed carisoprodol and, to a lesser degree, drug from an illegal street market.