Postmortem toxicology

Postmortem toxicology is the analyses of illegal and medicinal drugs in biological samples from deceased individuals. Such investigations are important in forensic cases to determine the cause of death, e.g. identifying possible overdoses. Interpretation of postmortem toxicological results requires caution, due to various factors that can influence drug concentrations after death. For example, drug concentrations in blood can increase after death, because of redistribution of some drugs from internal organs to blood. Therefore, samples for toxicological analyses are usually collected from peripheral blood, which is located far from internal organs. In some cases, however, it is not possible to sample peripheral blood, due to e.g. large trauma or severe decomposition of the corpse.

In the Forensic Toxicology and Pharmacology of Drugs of Abuse-research group we focus on postmortem toxicology in alternative matrices to blood, such as fluid from around the heart (pericardial fluid), fluid from the eye (vitreous humour), and skeletal muscle. Our research aims to improve toxicological assessment in complicated forensic cases, where blood is not available for sampling.

We also perform research aiming to improve the interpretation of postmortem ethanol findings. Since ethanol can be formed post-mortem, methods are needed to determine if ethanol was ingested before death. This can be particularly important in e.g. fatal car accidents. Research on postmortem ethanol is further described here.

Photo: Pixabay

Ongoing projects

Postmortem formation of GHB

Gamma-Hydroxybutyrate (GHB) is a substance that can be formed in the body after death. It is important to distinguish whether GHB detected in a deceased person is a result of intake of GHB or postmortem formation. In this project, postmortem toxicology data are linked to official causes of deaths, and we try to estimate the amount of postmortem formation of GHB that occurs at each concentration level of GHB. Additionally we evaluate whether the urine/blood concentration ratio is suitable to differentiate between GHB intake and postmortem formation.

Comparative study of different drugs in several alternative postmortem matrices

In this project, postmortem samples for toxicological analyses were collected from peripheral and cardiac blood, pericardial fluid, vitreous humour, and two types of skeletal muscle. Several papers originating from this project have already been published. Currently, we are studying:

Ethylglucuronide and ethylsulphate (metabolites of ethanol)
Amphetamines
Stability of opioids and benzodiazepines

Naloxone analysis in fatal opioid overdoses

In this project we investigate the prevalence of naloxone detection in blood samples from fatal opioid overdoses. Naloxone is an antidote to opioids, traditionally administered by the emergency medical services. In recent years, the development of naloxone as a nasal spray has made it easier to provide take-home naloxone to non-medical bystanders, aiming to prevent fatal opioid overdoses. It is not known how often naloxone is administered in opioid overdoses with a fatal outcome and this project aim to determine if naloxone nasal spray was used.

If you have questions about the projects or suggestions for research collaboration, please contact: Cecilie Thaulow (cectha@ous-hf.no) at the Department of Forensic Sciences, Oslo University Hospital, Oslo, Norway.

Publications

Øiestad EL, Øiestad ÅML, Middelkoop G, Brochmann GW, Thaulow CH, Vindenes V (2023)
Comparative Study of Postmortem Concentrations of Benzodiazepines and Z-Hypnotics in Several Different Matrices
J Anal Toxicol, 47 (3), 287-298
DOI 10.1093/jat/bkac106, PubMed 36542823

Havig SM, Vindenes V, Øiestad ÅML, Rogde S, Thaulow CH (2022)
Methadone, Buprenorphine, Oxycodone, Fentanyl and Tramadol in Multiple Postmortem Matrices
J Anal Toxicol, 46 (6), 600-610
DOI 10.1093/jat/bkab071, PubMed 34115841

Høiseth G, Fosen JT (2022)
[Ethanol is detected in the corpse, but had the deceased drunk alcohol?]
Tidsskr Nor Laegeforen, 142 (6)
DOI 10.4045/tidsskr.21.0896, PubMed 35383445

Pettersen S, Øiestad ÅML, Rogde S, Brochmann GW, Øiestad EL, Vindenes V (2021)
Distribution of tetrahydrocannabinol and cannabidiol in several different postmortem matrices
Forensic Sci Int, 329, 111082
DOI 1016/j.forsciint.2021.111082, PubMed 34775328

Midtlyng L, Høiseth G, Luytkis H, Kristoffersen L, Le Nygaard I, Strand MC, Arnestad M, Vevelstad M (2021)
Relationship between betahydroxybutyrate (BHB) and acetone concentrations in postmortem blood and cause of death
Forensic Sci Int, 321, 110726
DOI 10.1016/j.forsciint.2021.110726, PubMed 33631622

Oshaug K, Kronstrand R, Kugelberg FC, Kristoffersen L, Mørland J, Høiseth G (2021)
Frequency of postmortem ethanol formation in blood, urine and vitreous humor - Improving diagnostic accuracy with the use of ethylsulphate and putrefactive alcohols
Forensic Sci Int, 331, 111152
DOI 10.1016/j.forsciint.2021.111152, PubMed 34952291

Sidqey D, Liane VH, Kristoffersen L (2021)
Quantitative Determination of Ethyl Glucuronide and Ethyl Sulfate in Postmortem and Antemortem Whole Blood Using Phospholipid Removal 96-Well Plate and UHPLC-MS-MS
J Anal Toxicol, 45 (4), 378-388
DOI 10.1093/jat/bkaa108, PubMed 32816025

Bech AB, Clausen T, Waal H, Vindenes V, Edvardsen HE, Frost J, Skeie I (2020)
Post-mortem toxicological analyses of blood samples from 107 patients receiving opioid agonist treatment: substances detected and pooled opioid and benzodiazepine concentrations
Addiction, 116 (4), 845-855
DOI 10.1111/add.15211, PubMed 32738014

Bergh MS, Bogen IL, Wohlfarth A, Wilson SR, Øiestad ÅML (2019)
Distinguishing Between Cyclopropylfentanyl and Crotonylfentanyl by Methods Commonly Available in the Forensic Laboratory
Ther Drug Monit, 41 (4), 519-527
DOI 10.1097/FTD.0000000000000617, PubMed 30807539

Bergh MS, Bogen IL, Wilson SR, Øiestad ÅML (2018)
Addressing the Fentanyl Analogue Epidemic by Multiplex UHPLC-MS/MS Analysis of Whole Blood
Ther Drug Monit, 40 (6), 738-748
DOI 10.1097/FTD.0000000000000564, PubMed 30157097

Havig SM, Lea D, Krpo M, Skari RM, Gustavsen I, Høiseth G (2018)
Fatal Adverse Event with Dabigatran in Elderly Patient with Reduced Kidney Function
Basic Clin Pharmacol Toxicol, 123 (2), 221-226
DOI 1111/bcpt.12985, PubMed 29438599

Høiseth G, Arnestad M, Karinen R, Morini L, Rogde S, Sempio C, Vindenes V, Øiestad ÅML (2018)
Is Hair Analysis Useful in Postmortem Cases?
J Anal Toxicol, 42 (1), 49-54
DOI 1093/jat/bkx077, PubMed 28977558

Krpo M, Arnestad M, Karinen R (2018)
Determination of Acetaminophen, Dexchlorpheniramine, Caffeine, Cotinine and Salicylic acid in 100 μL of Whole Blood by UHPLC-MS/MS
J Anal Toxicol, 42 (2), 126-132
DOI 10.1093/jat/bkx089, PubMed 29186470

Krpo M, Luytkis HC, Haneborg AM, Høiseth G (2018)
A fatal blood concentration of 5-APB
Forensic Sci Int, 291, e1-e3
DOI 1016/j.forsciint.2018.08.044, PubMed 30228015

Mardal M, Johansen SS, Davidsen AB, Telving R, Jornil JR, Dalsgaard PW, Hasselstrøm JB, Øiestad ÅM, Linnet K, Andreasen MF (2018)
Postmortem analysis of three methoxyacetylfentanyl-related deaths in Denmark and in vitro metabolite profiling in pooled human hepatocytes
Forensic Sci Int, 290, 310-317
DOI 10.1016/j.forsciint.2018.07.020, PubMed 30107329

Oiestad AML, Berg T, Eliassen E, Wiklund T, Sand K, Oiestad EL (2018)
Separation of isomers of new psychoactive substances and isotope-labeled amphetamines using UHPSFC-MS/MS and UHPLC-MS/MS
J. Liq. Chromatogr. Relat. Technol., 41 (7), 391-400
DOI 10.1080/10826076.2017.1388818

Takitane J, Leyton V, Andreuccetti G, Gjerde H, Vindenes V, Berg T (2018)
Determination of cocaine, metabolites and a crack cocaine biomarker in whole blood by liquid-liquid extraction and UHPLC-MS/MS
Forensic Sci Int, 289, 165-174
DOI 10.1016/j.forsciint.2018.05.030, PubMed 29885489

Øiestad ÅML, Karinen R, Rogde S, Nilsen S, Boye Eldor KB, Brochmann GW, Arnestad M, Øiestad EL, Peres MD, Kristoffersen L, Vindenes V (2018)
Comparative Study of Postmortem Concentrations of Antidepressants in Several Different Matrices
J Anal Toxicol, 42 (7), 446-458
DOI 1093/jat/bky030, PubMed 29762694

Thaulow CH, Øiestad ÅML, Rogde S, Andersen JM, Høiseth G, Handal M, Mørland J, Vindenes V (2018)
Can measurements of heroin metabolites in post-mortem matrices other than peripheral blood indicate if death was rapid or delayed?
Forensic Sci Int, 290, 121-128
DOI 1016/j.forsciint.2018.06.041, PubMed 30015276

Thaulow CH, Øiestad ÅML, Rogde S, Karinen R, Brochmann GW, Andersen JM, Høiseth G, Handal M, Mørland J, Arnestad M, Øiestad EL, Strand DH, Vindenes V (2018)
Metabolites of Heroin in Several Different Post-mortem Matrices
J Anal Toxicol, 42 (5), 311-320
DOI 1093/jat/bky002, PubMed 29409037

Edvardsen HE, Tverborgvik T, Frost J, Rogde S, Morild I, Waal H, Clausen T, Slørdal L, Vindenes V (2017)
Differences in combinations and concentrations of drugs of abuse in fatal intoxication and driving under the influence cases
Forensic Sci Int, 281, 127-133
DOI 10.1016/j.forsciint.2017.10.045, PubMed 29128652

Hegstad S, Kristoffersen L, Liane VH, Spigset O (2017)
EtG and EtS in Autopsy Blood Samples With and Without Putrefaction Using UPLC-MS-MS
J Anal Toxicol, 41 (2), 107-113
DOI 10.1093/jat/bkw123, PubMed 27798076

Karinen R, Høiseth G (2017)
A literature review of blood concentrations of new psychoactive substances classified as phenethylamines, aminoindanes, arylalkylamines, arylcyclohexylamines, and indolalkylamines
Forensic Sci Int, 276, 120-125
DOI 10.1016/j.forsciint.2017.02.024, PubMed 28527345

Sundal MK, Lilleng PK, Barane H, Morild I, Vevelstad M (2017)
Asphyxiation death caused by oxygen-depleting cargo on a ship
Forensic Sci Int, 279, e7-e9
DOI 1016/j.forsciint.2017.08.024, PubMed 28890242

Vevelstad M, Drange E (2017)
[A bad boy among opioids]
Tidsskr Nor Laegeforen, 137 (20)
DOI 4045/tidsskr.17.0419, PubMed 29094571

Vevelstad M, Øiestad EL, Nerem E, Arnestad M, Bogen IL (2017)
Studies on Para-Methoxymethamphetamine (PMMA) Metabolite Pattern and Influence of CYP2D6 Genetics in Human Liver Microsomes and Authentic Samples from Fatal PMMA Intoxications
Drug Metab Dispos, 45 (12), 1326-1335
DOI 1124/dmd.117.077263, PubMed 28978661

Vevelstad M, Øiestad EL, Bremer S, Bogen IL, Zackrisson AL, Arnestad M (2016)
Is toxicity of PMMA (paramethoxymethamphetamine) associated with cytochrome P450 pharmacogenetics?
Forensic Sci Int, 261, 137-47
DOI 1016/j.forsciint.2016.02.027, PubMed 26930544

Høiseth G, Tuv SS, Karinen R (2016)
Blood concentrations of new designer benzodiazepines in forensic cases
Forensic Sci Int, 268, 35-38
DOI 10.1016/j.forsciint.2016.09.006, PubMed 27685473

Karinen R, Høiseth G, Svendsen KO, Rogde S, Vindenes V (2015)
A fatal intoxication with phenazone (antipyrine)
Forensic Sci Int, 248, e13-5
DOI 10.1016/j.forsciint.2015.01.001, PubMed 25631541

Berg T, Karlsen M, Oiestad AM, Johansen JE, Liu H, Strand DH (2014)
Evaluation of ¹³C- and ²H-labeled internal standards for the determination of amphetamines in biological samples, by reversed-phase ultra-high performance liquid chromatography-tandem mass spectrometry
J Chromatogr A, 1344, 83-90
DOI 10.1016/j.chroma.2014.04.020, PubMed 24780257

Eliassen E, Kristoffersen L (2014)
Quantitative determination of zopiclone and zolpidem in whole blood by liquid-liquid extraction and UHPLC-MS/MS
J Chromatogr B Analyt Technol Biomed Life Sci, 971, 72-80
DOI 10.1016/j.jchromb.2014.09.018, PubMed 25264915

Høiseth G, Fjeld B, Burns ML, Strand DH, Vindenes V (2014)
Long-term stability of morphine, codeine, and 6-acetylmorphine in real-life whole blood samples, stored at -20°C
Forensic Sci Int, 239, 6-10
DOI 10.1016/j.forsciint.2014.03.008, PubMed 24709028

Karinen R, Fosen JT, Rogde S, Vindenes V (2014)
An accidental poisoning with mitragynine
Forensic Sci Int, 245, e29-32
DOI 10.1016/j.forsciint.2014.10.025, PubMed 25453780

Karinen R, Tuv SS, Rogde S, Peres MD, Johansen U, Frost J, Vindenes V, Øiestad ÅM (2014)
Lethal poisonings with AH-7921 in combination with other substances
Forensic Sci Int, 244, e21-4
DOI 10.1016/j.forsciint.2014.08.013, PubMed 25216892

Karinen R, Vindenes V, Hasvold I, Olsen KM, Christophersen AS, Øiestad E (2014)
Determination of a selection of anti-epileptic drugs and two active metabolites in whole blood by reversed phase UPLC-MS/MS and some examples of application of the method in forensic toxicology cases
Drug Test Anal, 7 (7), 634-44
DOI 10.1002/dta.1733, PubMed 25331692

Krabseth H, Mørland J, Høiseth G (2014)
Assistance of ethyl glucuronide and ethyl sulfate in the interpretation of postmortem ethanol findings
Int J Legal Med, 128 (5), 765-70
DOI 10.1007/s00414-014-1031-z, PubMed 24935750

Thaulow CH, Høiseth G, Andersen JM, Handal M, Mørland J (2014)
Pharmacokinetic interactions between ethanol and heroin: a study on post-mortem cases
Forensic Sci Int, 242, 127-134
DOI 10.1016/j.forsciint.2014.06.032, PubMed 25050840

Al-Samarraie MS, Vevelstad M, Nygaard IL, Bachs L, Mørland J (2013)
[Intoxation with paramethoxymethamphetamine]
Tidsskr Nor Laegeforen, 133 (9), 966-9
DOI 10.4045/tidsskr.12.0417, PubMed 23652145

Amundsen I, Oiestad ÅM, Ekeberg D, Kristoffersen L (2013)
Quantitative determination of fifteen basic pharmaceuticals in ante- and post-mortem whole blood by high pH mobile phase reversed phase ultra high performance liquid chromatography-tandem mass spectrometry
J Chromatogr B Analyt Technol Biomed Life Sci, 927, 112-23
DOI 10.1016/j.jchromb.2012.12.039, PubMed 23380540

Arnestad M, Eldor KB, Stray-Pedersen A, Bachs L, Karinen R (2013)
Suicide due to cyclizine overdose
J Anal Toxicol, 38 (2), 110-2
DOI 10.1093/jat/bkt100, PubMed 24324230

Berg-Pedersen RM, Ripel A, Karinen R, Vevelstad M, Bachs L, Vindenes V (2013)
Codeine to morphine concentration ratios in samples from living subjects and autopsy cases after incubation
J Anal Toxicol, 38 (2), 99-105
DOI 10.1093/jat/bkt099, PubMed 24324229

Berg T, Jørgenrud B, Strand DH (2013)
Determination of buprenorphine, fentanyl and LSD in whole blood by UPLC-MS-MS
J Anal Toxicol, 37 (3), 159-65
DOI 10.1093/jat/bkt005, PubMed 23423312

Karinen R, Vindenes V, Morild I, Johnsen L, Le Nygaard I, Christophersen AS (2013)
Methyl tert-butyl ether (MTBE) detected in abnormally high concentrations in postmortem blood and urine from two persons found dead inside a car containing a gasoline spill
J Forensic Sci, 58 (5), 1393-1396
DOI 10.1111/1556-4029.12208, PubMed 23879346

Arnestad M (2012)
What is toxic in infants and children?
Forensic Sci Med Pathol, 9 (1), 94-5
DOI 10.1007/s12024-012-9371-9, PubMed 22926773

Fjeld B, Burns ML, Karinen R, Larssen B, Smith-Kielland A, Vindenes V (2012)
Long-term stability of GHB in post-mortem samples and samples from living persons, stored at -20°C, using fluoride preservatives
Forensic Sci Int, 222 (1-3), 47-51
DOI 10.1016/j.forsciint.2012.04.033, PubMed 22648054

Høiseth G, Majid U, Mørland J, Bramness JG, Molden E (2012)
CYP2C19 genetics in fatal carisoprodol intoxications
Eur J Clin Pharmacol, 68 (11), 1561-5
DOI 10.1007/s00228-012-1278-6, PubMed 22527345

Vevelstad M, Øiestad EL, Middelkoop G, Hasvold I, Lilleng P, Delaveris GJ, Eggen T, Mørland J, Arnestad M (2012)
The PMMA epidemic in Norway: comparison of fatal and non-fatal intoxications
Forensic Sci Int, 219 (1-3), 151-7
DOI 10.1016/j.forsciint.2011.12.014, PubMed 22257968