Journal of Clinical Forensic Medicine, Sep 1, 2003
A fatal case attributed to amlodipine intoxication is presented. The deceased was a 15-year-old g... more A fatal case attributed to amlodipine intoxication is presented. The deceased was a 15-year-old girl who allegedly ingested 14 10-rag Istin tablets. Amlodipine concentration in peripheral blood was determined (2.7 rag/L) and was compared with published therapeutic and toxic data for amlodipine and some other dihydropyridine calcium channel-blocking agents. Amlodipine concentrations in liver, blood, and stomach contents were also determined.
Introduction A case report involving repeated intoxications investigated by segmented hair analys... more Introduction A case report involving repeated intoxications investigated by segmented hair analysis is presented. A 41-year-old man intoxicated his 46-year-old wife several times over half a year. During this period of time the husband went away repeatedly for some days while the wife got sick. Often when he was away, she felt dizzy and nauseated and vomited. One night she was attacked by a man, who was later identified as the husband. The Police suspected the husband for several intoxication attempts on his wife. Methods Hair samples were collected from the top (5 cm long light brown hair with bleached stripes) and from the back of the head (2 cm long light brown unbleached hair) of the wife. Hair was sampled the 15-07-2013, so two of the suspected intoxication attempts (4-4 & 13-5-2013) are represented by segment 2 (1.5–4 cm). The segmented hair samples were washed, dissolved and analyzed for drugs and drugs of abuse by UPLC/TOF and quantified by UPLC/MS/MS (C. Montesano, SS. Johansen et al., JPBA 88 (2014) 295–306) Results Drug findings in head hair from the scalp and back (ng/mg) are shown in the Table. (0–1,5 cm) Scalp hair (4–5 cm) Back hair LOQ (1.5–4 cm) (0–2 cm) Caffeine 1.1 0.42 Trace 1.5 0.10 Codeine 0.009 0.031 nd 0.012 0.005 Lidocaine 0.009 0.024 0.0240 0.014 0.005 Morphine nd 0.006 nd nd 0.005 Tramadol 0.013 0.045 nd 0.015 0.010 O-desmethyltramadol Trace 0.008 nd Trace 0.005 Zolpidem 0.004 0.050 nd Trace 0.002 Diazepam nd Nd nd nd 0.002 Desmethyldiazepam 0.002 Nd nd nd 0.002 Segment 2 has highest drug concentrations of opioids and zolpidem. O-desmethyltramadol is a metabolite from tramadol, while morphine due to the low morphine:codeine ratio probably derives from codeine metabolism. After the violent attack the wife took diazepam a few times and the trace of the metabolite desmethyl-diazepam in the inner segment from scalp hair confirmed the ingestion. In general the drug levels in hair were low indicating few intake(s) and not sustained therapeutic use. The drug findings in the inner hair segment (0–1,5 cm) were com-parable with the drug levels found in the back hair, although the back hair was not bleached. Bleaching is reported to reduce the opioid content in hair from 57 to 94%, however the scalp hair was only partly bleached suggesting a lower loss and high ability to retain the drugs. Conclusion The case illustrates that hair is a valuable forensic specimen when natural processes have eliminated the drug from typical biological specimens such as blood and urine. It was possible to verify suspected intoxications by segmented hair analysis. The husband admitted the intoxications by mixing opioids and zolpidem in the wife’ coffee. He was sentenced to prison for 6 years.
Abstract Three known HPLC methods for the analysis of 1,2-dibromo-2,4-dicyanobutane (BCB) were co... more Abstract Three known HPLC methods for the analysis of 1,2-dibromo-2,4-dicyanobutane (BCB) were compared to evaluate the strength of the methods for the routine analysis of BCB in cosmetic products. Reversed- and normal-phase HPLC with UV detection were not suitable for routine analysis of BCB in cosmetics. Reversed-phase HPLC with electrochemical detection fulfilled the requirements of a method to be used on a routine basis.
A 79-year-old woman, with Parkinson's disease treated with cabergoline, was admitted to a... more A 79-year-old woman, with Parkinson's disease treated with cabergoline, was admitted to a hospital due to jaundice and weakness. She was found confused, absent minded, and died after 2 weeks. Autopsy showed an extrahepatic bile duct adenocarcinoma with spread to the gall bladder, the liver, and regional lymphnodes. While cleaning the hospital bed after her death, the nurses found several tablets hidden in the bed. Biological samples obtained at the autopsy were screened for common drugs and narcotics. Several drugs such as buprenorphine, codeine, paracetamol, and propranolol were detected in the blood at therapeutic levels. A method to determine cabergoline in whole blood and other forensic matrices was developed, and further investigations determined cabergoline concentrations in whole blood and liver tissue of 94 and 3100 microg/kg, respectively. The blood concentration was 100 times above the therapeutic level reported on cabergoline in plasma and in combination with her symptoms, suggest she took a fatal overdose of cabergoline.
causality. Severity was graded according to the Poisoning Severity Score. Results: Overall, 73 pa... more causality. Severity was graded according to the Poisoning Severity Score. Results: Overall, 73 patients, 36 (49.3%) males, 33 (45.2%) females, 4 (5.4%) sex unknown; mean age 3.6 years (range 0.3-15 years), were included. The route of exposure was oral in 62 cases, and rectal in 11 cases (all children ≤5 years). No effects were reported in 52 cases, minor symptoms in 20 and moderate symptoms in one case. There were no severe cases, and no fatalities (Table ). Minor signs consisted of mild gastrointestinal symptoms (n ¼ 16), somnolence (n ¼ 7), nervousness (n ¼ 2), hypertension (n ¼ 1), hypotension (n ¼ 1), and tachycardia (n ¼ 1). Moderate gastrointestinal symptoms (repeated vomiting, diarrhea) occurred in one case. Conclusion: Overdose with noscapine up to 32 mg/kg in children is tolerated with no or only mild effects, apart from one case with moderate gastrointestinal symptoms. Therefore, observation at home seems reasonable after overdose of up to 32 mg/kg in children.
A liquid chromatography mass spectrometric (LC/MS/MS) method has been developed for the determina... more A liquid chromatography mass spectrometric (LC/MS/MS) method has been developed for the determination of LSD, iso-LSD and the metabolite 2-oxo-3-hydroxy-LSD in forensic applications. The procedure involves liquid-liquid extraction of the analytes and LSD-D3 (internal standard) from 1.0 g whole blood or 1.0 ml urine with butyl acetate at pH 9.8. Confirmation and quantification were done by positive electrospray ionisation with a triple quadrupole mass spectrometer operating in multiple reaction monitoring (MRM) mode. Two MRM transitions of each compound were established and identification criteria were set up based on the retention time and the ion ratio. The curves of extracted standards were linear over a working range of 0.01-50 microg/kg for all transitions of LSD and iso-LSD. The limit of quantification was 0.01 microg/kg for LSD and iso-LSD. The method was applied to a case investigation involving a 26-year-old male suspected for having attempted homicide, where blood concentrations of LSD and iso-LSD were determined to 0.27 and 0.44 microg/kg, respectively. 2-Oxo-3-hydroxy-LSD was detected in the urine and confirmed the LSD abuse. The case illustrated the importance of analyte separation before MRM detection of a sample due to identical fragmentation ions of the isomers.
Recently there has been a strong public interest as well as politically on the abuse of ecstasy i... more Recently there has been a strong public interest as well as politically on the abuse of ecstasy in Denmark. The Department of Forensic Chemistry performs the toxicological analysis on the driving and criminal cases in Denmark and the post-mortem cases of East Denmark requested by the police. Screening for amphetamines and ecstasy is performed by RIA (amphetamine double antibody DPC) and confirmation and quantification by GC/MS analysis. In recent years there has been a change in the number of samples tested positive for designer amphetamines including MDMA (ecstasy), MDA, MDEA etc. The first two positive cases of designer ampetamines among 213 traffic cases requested for analysis by the police were detected in 1997 (2/213 ???0,9%). In 1999 4 cases were found, in 2000 were 9 cases observed and in 2001 were 6 positive cases among 201 analysed traffic cases. In these cases the dominating compound was MDMA followed by MDA. A few positive cases of MDEA were also observed and always in mi...
PROCEEDINGS OF THE 16TH INTERNATIONAL CONFERENCE ON ALCOHOL, DRUGS AND TRAFFIC SAFETY, 2002
In this investigation about 900 saliva samples, collected from drivers not suspected to be under ... more In this investigation about 900 saliva samples, collected from drivers not suspected to be under the influence of drugs or alcohol were screened by Cozarts "Drugs of Abuse Microplate EIA" for benzodiazepines, amphetamine, cannabis, cocaine/benzoylecgonine and opiates. The screening only includes few of the benzodiazepines on the market in Denmark, which means, that only a part of the saliva samples positive for benzodiazepines will be detected by the screening, and that the number of positive benzodiazepine samples will be underestimated. All the saliva samples positive for drugs by the screening were analysed by specific methods, mostly gaschromatography-mass spectrometry (GC-MS). Totally 2% of the investigated saliva samples were positive for drugs. 0.7% (6) of the investigated saliva samples were positive for benzodiazepines, 0.8% (7) for cannabis (tetrahydrocannabinol-THC), 0.3% (3) for opiates, 0.1 % (1) for amphetamine and 0.1% (1) for cocaine/benzoylecgonine. An evaluation of the importance of the saliva concentration will be described. (A) For the covering abstract of the conference, see ITRD Abstract No. E201067.
A 59-year-old woman who intentionally ingested 100-200 ml Basagran was taken to the hospital with... more A 59-year-old woman who intentionally ingested 100-200 ml Basagran was taken to the hospital with a cardiac arrest 2 days after she had consumed the herbicide. During this period she suffered vomiting, urination and diarrhoea and she was drowsy with a muddled speech. Biological samples obtained at the autopsy were analysed and presence of bentazone, alcohol and an active metabolite of citalopram were detected. Blood concentrations of bentazone, alcohol and desmethyl-citalopram were 625 mg/kg, 0.62 g/l and 0.03 mg/kg, respectively.
AbstractWe present a series of forensic cases measuring concentrations in hair of γ-hydroxybutyri... more AbstractWe present a series of forensic cases measuring concentrations in hair of γ-hydroxybutyric acid (GHB) and its glucuronide. The compounds were extracted from hair by incubation for 1.5 h in a 25:25:50 (v/v/v) mixture of methanol/acetonitrile/2 mM ammonium formate (8 % acetonitrile, pH 5.3). The compounds were determined by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). The limits of quantitation (LOQ) were 0.32 and 0.48 ng/mg hair for GHB and its glucuronide, respectively, and linearity up to 50 ng/mg. Extraction recoveries were 62–92 % for the analytes, and the accuracy was 90–108 %. Precision values expressed as relative standard deviations (%) obtained from daily controls were 9.1–11.3 % for GHB and 12.2–17.9 % for GHB glucuronide. Endogenous levels were up to 1.0 ng/mg for GHB and 1.2 ng/mg for GHB glucuronide in control subjects. In two GHB abusers, GHB was highly elevated (461–591 ng/mg), whereas GHB glucuronide was only slightly elevated in one of the subjects (1.7–3.1 ng/mg) and below the LOQ in the other. Thus, GHB glucuronide is not incorporated in hair in any appreciable amounts in GHB abusers and does not contribute diagnostically with regard to detection of exogenous exposure. To our knowledge, this is the first report to present GHB glucuronide in human hair.
Brain tissue is a useful supplement to blood in postmortem investigations, but reference concentr... more Brain tissue is a useful supplement to blood in postmortem investigations, but reference concentrations are scarce for many opioids. Heroin cases may be difficult to distinguish from morphine cases as heroin and its metabolites are rapidly degraded. We present concentrations from brain and blood and brain-blood ratios of 98 cases where morphine was quantified. These cases were grouped according to the cause of death: A: The compound was solely assumed to have caused a fatal intoxication. B: The compound presumably contributed to a fatal outcome in combination with other drugs, alcohol or disease. C: The compound was not regarded to be related to the cause of death. The cases were further classified as heroin cases if 6-acetyl-morphine or noscapine were detected. The analyses were carried out using solid-phase extraction or protein precipitation followed by ultra highperformance liquid chromatography coupled to mass spectrometry. The average brain-blood ratios of morphine were 1.2 and 1.8 for 69 morphine and 29 heroin cases, respectively. Differences in the brainblood ratios were found for cases where heroin and morphine were involved in the cause of death, either in combination or on its own (P < 0.001 and P = 0.004, respectively). However, the overlap between morphine and heroin cases precludes the use of the brain-blood ratio to distinguish heroin from morphine intake. Morphine-6-glucuronide and 6-acetyl-morphine were quantified in brain and blood in a subset of the samples, yielding median brain-blood ratios of 5.1 and 8.3, respectively. The brain concentrations may aid the toxicological investigation in cases where heroin or morphine intoxications are suspected, but blood is not available.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
In vitro and in vivo metabolism and detection of 3-HO-PCP, a synthetic phencyclidine, in human sa... more In vitro and in vivo metabolism and detection of 3-HO-PCP, a synthetic phencyclidine, in human samples and pooled human hepatocytes using high resolution mass spectrometry.
Journal of Clinical Forensic Medicine, Sep 1, 2003
A fatal case attributed to amlodipine intoxication is presented. The deceased was a 15-year-old g... more A fatal case attributed to amlodipine intoxication is presented. The deceased was a 15-year-old girl who allegedly ingested 14 10-rag Istin tablets. Amlodipine concentration in peripheral blood was determined (2.7 rag/L) and was compared with published therapeutic and toxic data for amlodipine and some other dihydropyridine calcium channel-blocking agents. Amlodipine concentrations in liver, blood, and stomach contents were also determined.
Introduction A case report involving repeated intoxications investigated by segmented hair analys... more Introduction A case report involving repeated intoxications investigated by segmented hair analysis is presented. A 41-year-old man intoxicated his 46-year-old wife several times over half a year. During this period of time the husband went away repeatedly for some days while the wife got sick. Often when he was away, she felt dizzy and nauseated and vomited. One night she was attacked by a man, who was later identified as the husband. The Police suspected the husband for several intoxication attempts on his wife. Methods Hair samples were collected from the top (5 cm long light brown hair with bleached stripes) and from the back of the head (2 cm long light brown unbleached hair) of the wife. Hair was sampled the 15-07-2013, so two of the suspected intoxication attempts (4-4 & 13-5-2013) are represented by segment 2 (1.5–4 cm). The segmented hair samples were washed, dissolved and analyzed for drugs and drugs of abuse by UPLC/TOF and quantified by UPLC/MS/MS (C. Montesano, SS. Johansen et al., JPBA 88 (2014) 295–306) Results Drug findings in head hair from the scalp and back (ng/mg) are shown in the Table. (0–1,5 cm) Scalp hair (4–5 cm) Back hair LOQ (1.5–4 cm) (0–2 cm) Caffeine 1.1 0.42 Trace 1.5 0.10 Codeine 0.009 0.031 nd 0.012 0.005 Lidocaine 0.009 0.024 0.0240 0.014 0.005 Morphine nd 0.006 nd nd 0.005 Tramadol 0.013 0.045 nd 0.015 0.010 O-desmethyltramadol Trace 0.008 nd Trace 0.005 Zolpidem 0.004 0.050 nd Trace 0.002 Diazepam nd Nd nd nd 0.002 Desmethyldiazepam 0.002 Nd nd nd 0.002 Segment 2 has highest drug concentrations of opioids and zolpidem. O-desmethyltramadol is a metabolite from tramadol, while morphine due to the low morphine:codeine ratio probably derives from codeine metabolism. After the violent attack the wife took diazepam a few times and the trace of the metabolite desmethyl-diazepam in the inner segment from scalp hair confirmed the ingestion. In general the drug levels in hair were low indicating few intake(s) and not sustained therapeutic use. The drug findings in the inner hair segment (0–1,5 cm) were com-parable with the drug levels found in the back hair, although the back hair was not bleached. Bleaching is reported to reduce the opioid content in hair from 57 to 94%, however the scalp hair was only partly bleached suggesting a lower loss and high ability to retain the drugs. Conclusion The case illustrates that hair is a valuable forensic specimen when natural processes have eliminated the drug from typical biological specimens such as blood and urine. It was possible to verify suspected intoxications by segmented hair analysis. The husband admitted the intoxications by mixing opioids and zolpidem in the wife’ coffee. He was sentenced to prison for 6 years.
Abstract Three known HPLC methods for the analysis of 1,2-dibromo-2,4-dicyanobutane (BCB) were co... more Abstract Three known HPLC methods for the analysis of 1,2-dibromo-2,4-dicyanobutane (BCB) were compared to evaluate the strength of the methods for the routine analysis of BCB in cosmetic products. Reversed- and normal-phase HPLC with UV detection were not suitable for routine analysis of BCB in cosmetics. Reversed-phase HPLC with electrochemical detection fulfilled the requirements of a method to be used on a routine basis.
A 79-year-old woman, with Parkinson&#39;s disease treated with cabergoline, was admitted to a... more A 79-year-old woman, with Parkinson&#39;s disease treated with cabergoline, was admitted to a hospital due to jaundice and weakness. She was found confused, absent minded, and died after 2 weeks. Autopsy showed an extrahepatic bile duct adenocarcinoma with spread to the gall bladder, the liver, and regional lymphnodes. While cleaning the hospital bed after her death, the nurses found several tablets hidden in the bed. Biological samples obtained at the autopsy were screened for common drugs and narcotics. Several drugs such as buprenorphine, codeine, paracetamol, and propranolol were detected in the blood at therapeutic levels. A method to determine cabergoline in whole blood and other forensic matrices was developed, and further investigations determined cabergoline concentrations in whole blood and liver tissue of 94 and 3100 microg/kg, respectively. The blood concentration was 100 times above the therapeutic level reported on cabergoline in plasma and in combination with her symptoms, suggest she took a fatal overdose of cabergoline.
causality. Severity was graded according to the Poisoning Severity Score. Results: Overall, 73 pa... more causality. Severity was graded according to the Poisoning Severity Score. Results: Overall, 73 patients, 36 (49.3%) males, 33 (45.2%) females, 4 (5.4%) sex unknown; mean age 3.6 years (range 0.3-15 years), were included. The route of exposure was oral in 62 cases, and rectal in 11 cases (all children ≤5 years). No effects were reported in 52 cases, minor symptoms in 20 and moderate symptoms in one case. There were no severe cases, and no fatalities (Table ). Minor signs consisted of mild gastrointestinal symptoms (n ¼ 16), somnolence (n ¼ 7), nervousness (n ¼ 2), hypertension (n ¼ 1), hypotension (n ¼ 1), and tachycardia (n ¼ 1). Moderate gastrointestinal symptoms (repeated vomiting, diarrhea) occurred in one case. Conclusion: Overdose with noscapine up to 32 mg/kg in children is tolerated with no or only mild effects, apart from one case with moderate gastrointestinal symptoms. Therefore, observation at home seems reasonable after overdose of up to 32 mg/kg in children.
A liquid chromatography mass spectrometric (LC/MS/MS) method has been developed for the determina... more A liquid chromatography mass spectrometric (LC/MS/MS) method has been developed for the determination of LSD, iso-LSD and the metabolite 2-oxo-3-hydroxy-LSD in forensic applications. The procedure involves liquid-liquid extraction of the analytes and LSD-D3 (internal standard) from 1.0 g whole blood or 1.0 ml urine with butyl acetate at pH 9.8. Confirmation and quantification were done by positive electrospray ionisation with a triple quadrupole mass spectrometer operating in multiple reaction monitoring (MRM) mode. Two MRM transitions of each compound were established and identification criteria were set up based on the retention time and the ion ratio. The curves of extracted standards were linear over a working range of 0.01-50 microg/kg for all transitions of LSD and iso-LSD. The limit of quantification was 0.01 microg/kg for LSD and iso-LSD. The method was applied to a case investigation involving a 26-year-old male suspected for having attempted homicide, where blood concentrations of LSD and iso-LSD were determined to 0.27 and 0.44 microg/kg, respectively. 2-Oxo-3-hydroxy-LSD was detected in the urine and confirmed the LSD abuse. The case illustrated the importance of analyte separation before MRM detection of a sample due to identical fragmentation ions of the isomers.
Recently there has been a strong public interest as well as politically on the abuse of ecstasy i... more Recently there has been a strong public interest as well as politically on the abuse of ecstasy in Denmark. The Department of Forensic Chemistry performs the toxicological analysis on the driving and criminal cases in Denmark and the post-mortem cases of East Denmark requested by the police. Screening for amphetamines and ecstasy is performed by RIA (amphetamine double antibody DPC) and confirmation and quantification by GC/MS analysis. In recent years there has been a change in the number of samples tested positive for designer amphetamines including MDMA (ecstasy), MDA, MDEA etc. The first two positive cases of designer ampetamines among 213 traffic cases requested for analysis by the police were detected in 1997 (2/213 ???0,9%). In 1999 4 cases were found, in 2000 were 9 cases observed and in 2001 were 6 positive cases among 201 analysed traffic cases. In these cases the dominating compound was MDMA followed by MDA. A few positive cases of MDEA were also observed and always in mi...
PROCEEDINGS OF THE 16TH INTERNATIONAL CONFERENCE ON ALCOHOL, DRUGS AND TRAFFIC SAFETY, 2002
In this investigation about 900 saliva samples, collected from drivers not suspected to be under ... more In this investigation about 900 saliva samples, collected from drivers not suspected to be under the influence of drugs or alcohol were screened by Cozarts "Drugs of Abuse Microplate EIA" for benzodiazepines, amphetamine, cannabis, cocaine/benzoylecgonine and opiates. The screening only includes few of the benzodiazepines on the market in Denmark, which means, that only a part of the saliva samples positive for benzodiazepines will be detected by the screening, and that the number of positive benzodiazepine samples will be underestimated. All the saliva samples positive for drugs by the screening were analysed by specific methods, mostly gaschromatography-mass spectrometry (GC-MS). Totally 2% of the investigated saliva samples were positive for drugs. 0.7% (6) of the investigated saliva samples were positive for benzodiazepines, 0.8% (7) for cannabis (tetrahydrocannabinol-THC), 0.3% (3) for opiates, 0.1 % (1) for amphetamine and 0.1% (1) for cocaine/benzoylecgonine. An evaluation of the importance of the saliva concentration will be described. (A) For the covering abstract of the conference, see ITRD Abstract No. E201067.
A 59-year-old woman who intentionally ingested 100-200 ml Basagran was taken to the hospital with... more A 59-year-old woman who intentionally ingested 100-200 ml Basagran was taken to the hospital with a cardiac arrest 2 days after she had consumed the herbicide. During this period she suffered vomiting, urination and diarrhoea and she was drowsy with a muddled speech. Biological samples obtained at the autopsy were analysed and presence of bentazone, alcohol and an active metabolite of citalopram were detected. Blood concentrations of bentazone, alcohol and desmethyl-citalopram were 625 mg/kg, 0.62 g/l and 0.03 mg/kg, respectively.
AbstractWe present a series of forensic cases measuring concentrations in hair of γ-hydroxybutyri... more AbstractWe present a series of forensic cases measuring concentrations in hair of γ-hydroxybutyric acid (GHB) and its glucuronide. The compounds were extracted from hair by incubation for 1.5 h in a 25:25:50 (v/v/v) mixture of methanol/acetonitrile/2 mM ammonium formate (8 % acetonitrile, pH 5.3). The compounds were determined by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). The limits of quantitation (LOQ) were 0.32 and 0.48 ng/mg hair for GHB and its glucuronide, respectively, and linearity up to 50 ng/mg. Extraction recoveries were 62–92 % for the analytes, and the accuracy was 90–108 %. Precision values expressed as relative standard deviations (%) obtained from daily controls were 9.1–11.3 % for GHB and 12.2–17.9 % for GHB glucuronide. Endogenous levels were up to 1.0 ng/mg for GHB and 1.2 ng/mg for GHB glucuronide in control subjects. In two GHB abusers, GHB was highly elevated (461–591 ng/mg), whereas GHB glucuronide was only slightly elevated in one of the subjects (1.7–3.1 ng/mg) and below the LOQ in the other. Thus, GHB glucuronide is not incorporated in hair in any appreciable amounts in GHB abusers and does not contribute diagnostically with regard to detection of exogenous exposure. To our knowledge, this is the first report to present GHB glucuronide in human hair.
Brain tissue is a useful supplement to blood in postmortem investigations, but reference concentr... more Brain tissue is a useful supplement to blood in postmortem investigations, but reference concentrations are scarce for many opioids. Heroin cases may be difficult to distinguish from morphine cases as heroin and its metabolites are rapidly degraded. We present concentrations from brain and blood and brain-blood ratios of 98 cases where morphine was quantified. These cases were grouped according to the cause of death: A: The compound was solely assumed to have caused a fatal intoxication. B: The compound presumably contributed to a fatal outcome in combination with other drugs, alcohol or disease. C: The compound was not regarded to be related to the cause of death. The cases were further classified as heroin cases if 6-acetyl-morphine or noscapine were detected. The analyses were carried out using solid-phase extraction or protein precipitation followed by ultra highperformance liquid chromatography coupled to mass spectrometry. The average brain-blood ratios of morphine were 1.2 and 1.8 for 69 morphine and 29 heroin cases, respectively. Differences in the brainblood ratios were found for cases where heroin and morphine were involved in the cause of death, either in combination or on its own (P < 0.001 and P = 0.004, respectively). However, the overlap between morphine and heroin cases precludes the use of the brain-blood ratio to distinguish heroin from morphine intake. Morphine-6-glucuronide and 6-acetyl-morphine were quantified in brain and blood in a subset of the samples, yielding median brain-blood ratios of 5.1 and 8.3, respectively. The brain concentrations may aid the toxicological investigation in cases where heroin or morphine intoxications are suspected, but blood is not available.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
In vitro and in vivo metabolism and detection of 3-HO-PCP, a synthetic phencyclidine, in human sa... more In vitro and in vivo metabolism and detection of 3-HO-PCP, a synthetic phencyclidine, in human samples and pooled human hepatocytes using high resolution mass spectrometry.
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