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AARHUS UNIVERSITY HEALTH DEPARTMENT OF FORENSIC MEDICINE 2 nd annual NAFT meeting and general assembly Aarhus, June 16 th -17 th 2016
Transcript
  • AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    2nd annual NAFT meeting and general assembly

    Aarhus, June 16th-17th 2016

    http://www.google.dk/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjsr5mi-qPKAhUGl3IKHQaLBSYQjRwIBw&url=http://kendte.dk/regentparret-bruger-juleferien-paa-kultur/&bvm=bv.111396085,d.bGQ&psig=AFQjCNHLCI1VgtlJu68wiyh28QvvGJVI-A&ust=1452677059435058

  • 2

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    Welcome

    The organising committee and the staff at the Department of Forensic Medicine, Section for Forensic

    Chemistry welcome you all to the 2nd annual NAFT meeting and general assembly.

    We are very pleased to give you 23 oral presentations representing almost all the laboratories

    working with forensic toxicology in the Nordic countries. The abstracts describe many different

    aspects of modern forensic toxicology and represent high international quality and cutting edge

    research within our field.

    The six workshops cover a wide range of areas within forensic toxicology addressing analytical,

    metabolism methodologies, interpretation of results and practical improvements in the laboratory.

    The intention with the three parallel workshop sessions is to create an informal atmosphere open

    for sharing experiences and discussions.

    We would like to thank all the vendors present at the meeting. Their presence contributes to qualify

    the new technical solutions as well as making the meeting possible. The majority have a booth in the

    hotel foyer and you are more than welcome to pay them a visit.

    We are most grateful to all our colleagues who have contributed to this meeting with scientific and

    workshop presentations as well as arranging and chairing the sessions. In total 39 of you are

    contributing at the meeting which is very impressive. Thank you!

    Finally we will like to encourage you all to participate actively in networking and discussions thus

    creating a successful NAFT meeting. We hope you will enjoy your stay in Aarhus.

    The organising committee

    Mette Findal Andreasen Senior Researcher, PhD

    Jakob Ross Jornil Forensic Chemist, PhD

    Mogens Johannsen Professor, PhD

    Jørgen Bo Hasselstrøm Senior Researcher, PhD

  • 3

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    Contents

    Schedule…………………………………………………………………………………………………………………………………………. 4

    Workshops..……………………………………………………………………………………………………………………………………. 6

    Abstracts…………………………………………………………………………………………………………………………………………. 8

    Participants…………………………………………………………………………………………………………………………………….. 31

    NAFT 2017………………………………………………………………………………………………………………………………………. 33

  • 4

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    Schedule - Thursday 16th June 2016

    Time Title

    09.00 - 10.00 Registration and coffee

    10.00 - 10.10 Welcome

    10.10 - 12.10 Scientific session I: Analysis and pharmacology Chairman: Robert Kronstrand, National Board of Forensic Medicine, Linköping, Sweden

    O1 Ion-source -independent library-based identification and concurrent quantification of new psychoactive substances without authentic reference standards by gas chromatography –atmospheric pressure chemical ionization quadrupole time-of-flight mass spectrometry coupled to nitrogen chemiluminescence detection (GC-NCD-APCI-QTOFMS) Samuel Mesihää, University of Helsinki, Finland

    O2 Parent drug calibration for the determination of metabolite to parent drug ratios in post-mortem blood by UPLC-DAD-CAD Jenni Viinamäki, University of Helsinki, Finland

    O3 Method development for determination of new psychoactive substances in urine using solid phase extraction and LC-QTOF Sofia Lindahl, St. Olav University Hospital, Trondheim, Norway

    O4 Screening for Therapeutic and Illicit Drugs in Airplane Wastewater – a New Matrix for Mapping Patterns of Drug Use and Abuse Marie Mardal, University of Copenhagen, Denmark

    O5 Quantitative screening of synthetic cannabinoids in urine using UHPLC-QTOF-MS Per Ole M. Gundersen, St Olav University Hospital, Trondheim, Norway

    O6 The INTOx project: quantification of ten sedatives and analgesics in blood from patients undergoing intensive care treatment Anna Johansson, National Board of Forensic Medicine, Linköping, Sweden

    O7 Analysis of hair in post mortem cases can reveal use of drugs not detected in blood Marianne Arnestad, Norwegian Institute of Public Health, Norway

    O8 Deposition of diazepam and its metabolites in hair following a single dose of diazepam Sys Stybe Johansen, University of Copenhagen, Denmark

    O9 Targeted proteomics of CYP1A2 and CYP3A4 in post-mortem liver tissue Jakob Hansen, Aarhus University, Denmark

    12.10 - 13.20 Lunch

    13.20 - 15.20 Scientific session II: pharmacology and interpretation Chairman: Kristian Linnet, University of Copenhagen, Denmark

    O10 In vitro metabolism studies on new designer benzodiazepines Carolina Noble, University of Copenhagen, Denmark

    O11 Metabolic profiling using retrospective UPLC-HR-TOF-MS data from forensic toxicology screenings Kirstine Lykke Nielsen, Aarhus University, Denmark

    O12 Ethanol elimination at low concentrations in drunk drivers Gudrun Høiseth, Norwegian Institute of Public Health, Norway

    O13 Post-mortem levels and tissue distribution of codeine, codeine-6-glucuronide, nor-codeine, morphine and morphine glucuronides in a series of codeine-related deaths Joachim Frost, St Olav University Hospital, Trondheim, Norway

    O14 Distribution of QT-prolonging drugs and metabolites between cardiac tissue and femoral blood in a psychiatric population Christian Reuss Mikkelsen, Aarhus University, Denmark

    O15 Comparison of antidepressiva concentrations in different post mortem media Åse Marit Leere Øiestad, Norwegian Institute of Public Health, Norway

    O16 Testosterone levels in forensic cases compared to testosterone levels in long-acting replacement therapy with intramuscular testosterone undecanoate Yvonne Lood, National Board of Forensic Medicine, Linköping, Sweden

    O17 Reference values of Lithium in post-mortem blood Carl Söderberg, National Board of Forensic Medicine, Linköping, Sweden

    O18 Beta-hydroxybutyrate and the post mortem diagnosis of ketoacidosis Elli Tyrkkö, National Board of Forensic Medicine, Linköping, Sweden

    15.20 - 15.50 Coffee

    15.50 - 16.50 General assembly

    19.00 - Social dinner (Restaurant, Scandic Aarhus City Hotel)

  • 5

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    Schedule – Friday 17th June 2016

    Time Title

    08.30 - 09.30 Scientific session III: interpretation and miscellaneous Chairman: Svava Thordardottir, University of Iceland, Iceland

    O19 Deaths attributed to 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (α-PVP) Robert Kronstrand, National Board of Forensic Medicine, Linköping, Sweden

    O20 An increase in fentanyl-related deaths during the winter 2015/2016 Gunilla Thelander, National Board of Forensic Medicine, Linköping, Sweden

    O21 Trends in fatal poisonings by prescription drugs in Finland since 2000 lkka Ojanperä, University of Helsinki, Finland

    O22 Reoffending in drugrelated crimes in Sweden, 1993 – 2013 Johan Ahlner, National Board of Forensic Medicine, Linköping, Sweden

    O23 Experiences in an EU project “Strengthening and modernizing the forensic services in Kosovo” Ilpo Rasanen, National Institute for Health and Welfare (THL), Helsinki, Finland

    09.30 - 09.45 Coffee

    09.45 - 11.00 Parallel workshops 1-3

    W1 Keeping the TOF library updated

    W2 Forensic applications of in vitro metabolism

    W3 Improvements in the laboratory I

    11.00 - 11.30 Coffee

    11.30 - 12.45 Parallel workshops 4-6

    W4 Interpretation of post-mortem results

    W5 Metabolomics in forensic toxicology

    W6 Improvements in the laboratory II

    12.45 - Lunch to go

  • 6

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    Workshops

    Workshop no. 1: Keeping the TOF library updated Chairman: Petur Dalsgaard, University of Copenhagen, Denmark

    This workshop will focus on how to keep our TOF libraries updated. New psychoactive substances

    continuously appear on the illegal market in the Nordic countries and the rest of the world.

    Therefore, it is increasingly important to collaborate and share information on new substances. The

    following four lectures will tell how they keep their TOF libraries updated using different HR-TOF

    instruments e.g. from Waters, Bruker, Agilent, Sciex and Thermo.

    Petur Weihe Dalsgaard, University of Copenhagen, Denmark

    Mette Findal Andreasen, Aarhus University, Denmark

    Per Ole M. Gundersen, St. Olavs Hospital, Trondheim, Norway

    Christian Brinch Mollerup, University of Copenhagen, Denmark.

    Workshop no. 2: Forensic applications of in vitro metabolism Chairman: Jakob Ross Jornil, Aarhus University, Denmark

    The workshop is an opportunity to get introduced to or to expand knowledge of in vitro metabolism in a forensic context.

    Overview on different in vitro techniques for metabolite identification Ariane Wohlfarth, National Board of Forensic Medicine, Division of Drug Research, Department of Medical and Health Sciences, Linköping University

    In vitro metabolism of synthetic cannabinoids Niels Bjerre Holm, Department of Forensic Medicine, Section of Forensic Chemistry, University of Copenhagen

    In vitro - in vivo correlations Svante Vikingsson, National Board of Forensic Medicine, Division of Drug Research, Department of Medical and Health Sciences, Linköping University

    In vitro - in vivo extrapolation, using in silico techniques to predict ADME Jakob Ross Jornil, Section for Forensic Chemistry, Department of Forensic Medicine, Aarhus University

    Workshop no. 3: Improvements in the laboratory I Chairman: Jørgen Bo Hasselstrøm, Aarhus University, Denmark.

    This workshop will focus on the daily routines in the forensic toxicology laboratory and how to improve the production. The workshop will consist of a series of short informal presentations all open for discussion and questions. Issues could be stability of compounds, pre-analytical considerations (sample tubes and preservation), LEAN initiatives etc.

    Studies on test tubes with different sodium fluoride content Gunnel Nilsson and Nina Rinquist, National Board of Forensic Medicine, Linköping, Sweden

    Pre-analytical stability and sample handling Jørgen Bo Hasselstrøm, Aarhus University, Denmark

    LEAN/LIMS/Automation Brian Rasmussen, University of Copenhagen, Denmark

  • 7

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    Workshops (continued)

    Workshop no. 4: Interpretation of post-mortem results Chairman: Marianne Arnestad, Norwegian Institute of Public Health, Norway and Ljubica Vukelic Andersen, Aarhus University, Denmark.

    The workshop will go through standard interpretation of toxicological results from autopsies with focus on pitfalls and the importance of clinical medical information.

    Pitfalls in interpretation of toxicological results from autopsies – introduction

    Liliana Bachs, Norwegian Institute of Public Health, Norway

    Importance of clinical medical information

    Ljubica Vukelic Andersen/Eva Sædder, Aarhus University, Denmark

    Reference concentrations for interpreting drug related deaths

    Ilkka Ojanperä, University of Helsinki, Finland

    Importance of pharmacogenetics in toxicological interpretation

    Pernilla Haage, National Board of Forensic Medicine, Linköping, Sweden

    Use of alternative matrixes in toxicological interpretation

    Joachim Frost, St. Olavs Hospital, Trondheim, Norway

    General discussion

    Workshop no. 5: Metabolomics in forensic toxicology Chairman: Mogens Johannsen, Aarhus University, Denmark This workshop will give a short introduction to untargeted metabolomics. Thereafter an introduction to how we apply a metabolomic analysis on routine forensic data to assess drug metabolism and toxicology.

    Kirstine Lykke Nielsen and Mogens Johannsen, Aarhus University, Denmark

    Workshop no. 6: Improvements in the laboratory II Chairman: Jørgen Bo Hasselstrøm, Aarhus University, Denmark This workshop will focus on the daily routines in the forensic toxicology laboratory and how to improve the production. The workshop will consist of a series of short informal presentations all open for discussion and questions. We will continue from workshop no. 3 with focus on automation and LIMS.

    Automated blood pipetting to glass tubes and 96-well format with Hamilton robots

    Martin Josefsson and Gunnel Nilsson, National Board of Forensic Medicine, Linköping, Sweden

    LIMS and automation

    Åse Marit Leere Øiestad, Norwegian Institute of Public Health, Norway

    How low can you go? Using a microbalance for preparation of stock solutions

    Jakob Ross Jornil, Aarhus University, Denmark

  • 8

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    Abstracts

    O1

    Ion-source -independent library-based identification and concurrent quantification of new

    psychoactive substances without authentic reference standards by gas chromatography –

    atmospheric pressure chemical ionization quadrupole time-of-flight mass spectrometry coupled to

    nitrogen chemiluminescence detection (GC-NCD-APCI-QTOFMS)

    Samuel Mesihääa, Ilkka Ojanperäa, Ilpo Rasanena, Anna Pelandera & Raimo Ketolaa

    aUniversity of Helsinki, Department of Forensic Medicine

    Contact information (e-mail(s)): [email protected]

    Introduction Two novel concepts are presented

    Comparison between GC-APCI and LC-ESI product ion spectra for drugs

    We investigated the feasibility of using a commercial drug spectrum library produced by LC-ESI-

    QTOFMS as a reference for the identification of spectra produced by GC-APCI-QTOFMS. An in-house

    GC-APCI-QTOFMS library was built containing spectral data of 50 compounds belonging to different

    classes of drugs, such as amphetamines, benzodiazepines, synthetic cathinones, synthetic

    cannabinoids and opioids. The GC-APCI-QTOFMS spectra were measured at three different collision

    energy levels similarly to the commercial spectral library.

    Quantification of new psychoactive substances (NPS) without reference standards

    A vast majority of psychoactive drugs (> 90%) contain nitrogen. The equimolar quantification

    capability of the nitrogen chemiluminescence detector was demonstrated by analysing the following

    five NPS at five concentration levels between 0.17-1.7 µg/ml spiked post-extraction in sheep blood:

    bupropion, desoxypipradrol (2-DPMP), mephedrone, methylone and naphyrone.

    Materials and methods A 7890B Series GC System equipped with a 7693 Automatic Liquid Sampler

    and a split/split less injector was coupled through a G3180B Two-Way Splitter with Makeup Gas to

    an APCI 6540 UHD Accurate-Mass QTOF mass analyser and a 255 Nitrogen Chemiluminescence

    Detector (all Agilent Technologies).

    Results APCI generated a protonated precursor ion for most of the 50 compounds. The protonated

    MS/MS spectra were highly similar between the LC-ESI and GC-APCI libraries in terms of ion

    abundance ratios and mass accuracy. We conclude that the LC-ESI commercial mass spectral library

    can be used in connection with other platforms provided that the [M+H]+ is produced. Derivatized

    compounds and compounds associated with neutral loss at GC-APCI require separate libraries.

    The equimolarity of NCD was on average 98.7%, and the range of individual equimolarity

    determinations was 76.7 – 130.1%, providing acceptable quantitative results in the present study

    setting. However, extraction recovery was not considered at this point.

    Conclusion The current analysis platform affords a promising approach to instant simultaneous

    qualitative and quantitative analysis of drugs in the absence of authentic reference standards.

    Future research will concentrate on standardizing the GC-APCI ionization, as well as improving the

    sensitivity of the NCD determination.

  • 9

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    O2

    Parent drug calibration for the determination of metabolite to parent drug ratios in post-mortem

    blood by UPLC-DAD-CAD

    Jenni Viinamäkia, Ilkka Ojanperäa

    aDepartment of Forensic Medicine, University of Helsinki, Finland

    Contact information (e-mail(s)): [email protected]

    Introduction There is a constant demand for the quantification of drug metabolites within post-

    mortem toxicology. However, the information of metabolite concentrations and metabolite to

    parent ratios in post-mortem blood is scarce due to limited availability and high price of primary

    reference standards. In this study, ultra-high performance liquid chromatography coupled with

    photodiode array detection and corona charged aerosol detection (UPLC-DAD-CAD) was utilized for

    the concurrent quantification of 23 drug metabolites using the corresponding parent drug for

    calibration. After validation of this secondary calibration method, 633 previously analysed post-

    mortem blood samples were retrospectively re-processed to discover the metabolite to parent

    ratios of six toxicologically relevant drugs.

    Materials and methods Blood samples were extracted in basic conditions and chromatographic

    separation was performed with a C18 column using a mobile phase gradient consisting of an

    aqueous solution of trifluoroacetic acid and methanol. One-point calibration was performed with the

    parent drug. The linearity was tested at concentration range from 0.05 to 5.0 mg/L.

    Results Based on the secondary calibration, the quantitative results for the N-demethylated

    metabolites by both detectors were similar to those obtained by the ordinary calibration using

    primary reference standards. With O-demethylated metabolites, differences in UV spectra and

    retention times caused larger biases. The metabolite to parent ratios measured in this study fell

    within the normal ratios utilized in therapeutic drug monitoring and were comparable to those

    reported in post-mortem material.

    Conclusion This study presents a cost-effective and straightforward method for the quantification of

    the parent drug and its metabolites concurrently, with use of the parent drug reference standard

    only. The possibility to utilize historic one-point calibration reduces the calibration workload

    compared to mass spectrometric methods. We anticipate that the readily accumulating data by the

    presented method will add to the scarce literature of drug metabolites in post-mortem samples.

    Connected to the cause-of-death information, the metabolite to parent ratios will provide an

    additional reference for interpretation of toxicological results.

  • 10

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    O3

    Method development for determination of new psychoactive substances in urine using solid phase

    extraction and LC-QTOF

    Sofia Lindahla and Andreas Westina

    aDepartment of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway

    Contact information (e-mail): [email protected]

    Introduction During the last decade there has been a rapid and continuous growth in the availability

    and use of novel psychoactive substances (NPS) across the world. Forensic laboratories have to

    continuously adapt their urinalysis procedures in order to keep track with the ever-changing NPS

    landscape. The aim of your study was to develop a generic method for analysis of NPS in urine to

    simplify the addition of new compounds with time.

    Materials and methods Fifty NPS/NPS metabolites from different drug classes (e.g. benzodiazepines,

    cathinones, phenethylamines and tryptamines) were selected based on the NPS prevalence in

    seizures made by Norwegian police and customs. For sample preparation solid phase extraction was

    selected, since then removal of interfering matrix components and up-concentration of low

    abundance analytes can be combined. Two different SPE materials were evaluated; cation exchange

    (Evolute Express CX, Biotage) and hydrophilic lipophilic balanced copolymer (Oasis Prime HLB,

    Waters). Standards and spiked urine samples were analysed with UHPLC-QTOF (Agilent). Separation

    was performed using an HSS T3 analytical column (2.1 x 100 mm, 1.8 µm, Waters), with gradient

    elution (0.025 % formic acid and 5 mM ammonium format in water and 0.05% formic acid in

    acetonitrile).

    Preliminary results Since this project is still in the method development phase the results presented

    will be focused on comparison of the extraction yield and matrix effects using the different SPE

    materials and on the development of the LC-QTOF method. Discussion of advantages and

    disadvantages of using a generic method compared to several targeted methods will also be

    discussed.

  • 11

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    O4

    Screening for Therapeutic and Illicit Drugs in Airplane Wastewater – a New Matrix for Mapping

    Patterns of Drug Use and Abuse

    Marie Mardala, Frank M. Aarestrupb, Brian Schou Rasmussena, Christian Brinch Mollerupa, Petur

    Weihe Dalsgaarda, Kristian Linneta

    aSection of Forensic Chemistry, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of

    Copenhagen, Copenhagen, Denmark, bNational Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark.

    Contact information (e-mail(s)): [email protected], [email protected]

    Introduction There is limited knowledge on the global prescription and consumption patterns of

    therapeutic drugs (TD) and illicit drugs (ID). Pooled urine analysis (PUA) is valuable for obtaining

    snap-shots of where and when TD and ID are consumed. However, PUA fails to cover targets

    excreted through faeces. Wastewater has previously been used for local-based wastewater-based

    epidemiology (WBE) and drug screening. It is however difficult to study the global epidemiology due

    to difficulties in obtaining samples.

    The aim of the study was to test the detectability of TD and ID in airplane wastewater samples

    categorized according to their geographical origin.

    Materials and methods Wastewater samples (n= 17) were collected from long-distance flights

    arriving at Copenhagen airport. The samples were prepared according to a previously described fully

    automated setup (Andersen et al. JAT, 2012), with enzymatic conjugate cleaving followed by either

    precipitation or solid phase extraction (SPE). Aliquots from precipitated samples were analysed by

    UPLC-QTOF in data-independent acquisition mode (MSE) controlled by UNIFI software (Waters) with

    a 3,145 compound library for target and suspect screening. SPE samples aliquots were injected onto

    UPLC-MS/MS systems with previously validated methods. TD were grouped according to their

    Anatomical Therapeutic Chemical (ATC) codes. Principal component analysis (PCA) was performed

    with therapeutic subgroup ATC codes as variables.

    Results Identification confidence was assigned to three levels based on: retention time error, mass

    error, and number of identifying fragments, detection on both instruments and targets per

    compound, with level 1 being the highest level of confidence. More than 74 % of the detected TD

    belonged to the anatomical main groups for drugs acting on the neurological, respiratory, or

    cardiovascular systems. Distributed on 89 different compounds, the accumulated number of TD and

    ID detected in the wastewater samples were: 84 (level 1), 234 (level 2), and 433 (level 3). Cocaine

    and methamphetamine were both identified in two samples. The screening also identified drugs

    mainly excreted in faeces, e.g. dipyramidol. The first two principle components in the PCA separated

    three clusters of wastewater samples based on geographical origin of the airplanes.

    Conclusion Airplane wastewater analysis is a useful addition to PUA for identifying targets for WBE

    and toxicological analysis.

    mailto:[email protected]

  • 12

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    O5

    Quantitative screening of synthetic cannabinoids in urine using UHPLC-QTOF-MS

    Per Ole M. Gundersena, Olav Spigseta,b, Martin Josefssonc,d

    aDepartment of Clinical Pharmacology, St Olav University Hospital, Trondheim, Norway

    bDepartment of Laboratory Medicine, Children’s and Women’s Health, Norwegian University of Science and Technology,

    Trondheim, Norway cDepartment of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden

    dDepartment of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden

    Contact information (e-mail(s)): [email protected]

    Introduction Synthetic cannabinoids share structural and pharmacodynamical properties with the

    psychoactive substance Δ9-tetrahydrocannabinol (THC) but they often have higher affinity to the

    cannabinoid receptors. This makes them potentially more toxic than THC. Designer drug

    manufacturers bypass the legislations by continuously introducing new analogues to the market.

    This calls for drug screening methods with a panel of analytes that can easily be updated.

    Materials and methods High resolution mass spectrometry technology such as liquid

    chromatography quadrupole time of flight mass spectrometry (LC-QTOF-MS) has been proven

    sensitive and accurate for drug screening purposes and methods can relatively easily be updated.

    Urine is the sample matrix of choice for screening due to the ease of sampling and the time window

    of detection.

    The aim of this study was to develop a sensitive quantitative screening method for a selection of

    nine synthetic cannabinoids (AB-Fubinaca, AB-Pinaca, AB-Chminaca, BB-22, PB-22, 5F-PB-22, AKB48,

    5F-AKB48 and UR-144) with different core structures and chemical properties. The target was to

    reach a lower limit of quantification (LOQ) of 0.1 ng/ml for many of the analytes using an automated

    preparation. Samples were prepared by 96 well-plate supported liquid extraction (SLE) followed by

    analysis on an Agilent 6550 iFunnel QTOF combined with a 1290 LC system.

    Results The advantage of SLE is an easy sample protocol but the technique has limitation in the

    clean-up efficiency. Together with a two times pre-concentration this caused a pronounced matrix

    effect with up to 45 % suppression (between 45 % and -15 % for the different metabolites) of the

    analyte signal. This illustrates the analytical difficulties reaching the desired LOQs for these

    substances.

    Conclusion Analytical and practical issues particularly regarding choice of consumables and reagents

    in the analytical method will be discussed. Thoughts around confirming findings and updating the

    panel of the method will be covered.

  • 13

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    O6

    The INTOx project: quantification of ten sedatives and analgesics in blood from patients

    undergoing intensive care treatment

    Anna Johanssona, Ulrica Lennbornb, Robert Kronstranda c, Markus Romana, Håkan Sandlerd e, Elisabet

    Nielsenf, Johan Ahlnera,c, Fredrik C Kugelberga,c, Sten Rubertssonb

    aDepartment of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine; Linköping, Sweden;

    bDepartment of Surgical Sciences/Anaesthesiology and Intensive Care Medicine, Uppsala University, Uppsala, Sweden;

    cDepartment of Medical and Health Sciences, Division of Drug Research, Linköping University, Linköping, Sweden;

    dDepartment of Forensic Medicine, National Board of Forensic Medicine, Uppsala, Sweden;

    eDepartment of Surgical

    Sciences/Forensic Medicine, Uppsala University, Uppsala, Sweden; fDepartment of Pharmaceutical Biosciences, Uppsala

    University, Uppsala, Sweden

    Contact information (e-mail(s)): [email protected]

    Introduction The INTOx project is a collaborative project between the general intensive care unit (ICU) at

    the University Hospital of Uppsala, Sweden and the Swedish National Board of Forensic Medicine. The

    aim of this project is to study blood concentrations of ten sedatives and analgesics regularly used in the

    ICU and also relate the concentrations to dosage, degree of organ failure and clinical response. It will also

    be studied whether intoxicated patients have taken drugs that initially were not suspected. In patients

    that die during intensive care, antemortem and post-mortem blood drug concentrations will be

    compared.

    Patients and methods All patients over the age of seven, admitted to the general ICU at Uppsala

    University Hospital, were included in the study. The first study period lasted for two months and the

    second study period for three months. Blood samples were collected, according to standardized

    procedures, when the patient arrived to the ICU and then twice daily until discharged. The samples were

    screened for pharmaceuticals and drugs of abuse using liquid chromatography/time-of-flight mass

    spectrometry (LC-TOF-MS). Propofol, thiopental, midazolam, dexmedetomidine, clonidine, ketamine,

    fentanyl, morphine, ketobemidone and paracetamol were quantified using gas chromatography (GC), GC-

    MS or LC-MS/MS.

    Results During the first study period 125 patients, including 14 intoxications, were treated at the general

    ICU. Ten patients died. During the second study period 174 patients, including 20 intoxications were

    treated and 12 patients died. The most commonly administrated sedatives and analgesics were propofol

    and fentanyl. The mean, median and range concentrations of propofol in 935 samples were 1.13 µg/g, 0.9

    µg/g and 0.05-16.5 µg/g, respectively. The mean, median and range concentrations of fentanyl in 1031

    samples were 0.99 ng/g, 0.71 ng/g and 0.05-9.4 ng/g, respectively.

    Conclusion Quantification of sedatives and analgesics routinely used to treat patients in the ICU can

    possibly result in more individualized dosing strategies. With an optimized dose the patient need less

    time in the ICU and in the long run this lowers health care costs. Furthermore, both antemortem and

    post-mortem reference concentrations for such drugs could be of great aid to the forensic pathologist.

  • 14

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    O7

    Analysis of hair in post mortem cases can reveal use of drugs not detected in blood

    Gudrun Høisetha, Marianne Arnestada, Ritva Karinena, Luca Morinib, Sidsel Rogdea,c, Cristina Sempioa,

    Vigdis Vindenesa,c, Åse Marit Leere Øiestada

    aNorwegian Institute of Public Health, Domain for Forensic Sciences, Oslo, Norway

    bDepartment of Public Health, Experimental and Forensic Medicine, University of Pavia, Italy

    cInstitute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway

    Contact information (e-mail(s)): [email protected]

    Introduction: In post mortem cases, detection of drugs in blood is most relevant with regard to

    determining cause of death. However, it is sometimes also of interest to gain information regarding

    the deceased´s use of drugs in the period before death. The aim of this study was to compare results

    from analyses of a broad repertoire of psychoactive medicinal drugs in blood and hair samples from

    post mortem cases.

    Materials and Methods: Forensic autopsy cases in which intake of drugs was suspected were

    included. Post mortem blood collected from the femoral vein and hair samples from the posterior

    vertex were collected simultaneously, and analysed for a number of psychoactive medicinal drugs,

    mainly benzodiazepines, antidepressants and antipsychotics. Blood was analysed using validated GC-

    MS, LC-MS or UPLC-MS/MS methods, and 3 cm long proximal hair segments were analysed by a

    validated LC-MS/MS method. Substances not included in both the blood and hair methods were

    excluded. Cases where external contamination of hair was suspected were also not included in the

    study.

    Results: Blood and hair samples from 55 post mortem cases were included in the study. Drug(s)

    were detected in hair or blood in 53 of the 55 cases (96%). The most frequently detected drugs in

    hair or blood was diazepam, followed by clonazepam. In total, hair analyses gave information of use

    of drugs not detected in blood in 47 of the 55 cases (85%). In these cases, additional use of 1-10

    drugs (median 2) was revealed. In only two cases (4%), benzodiazepines were detected in blood,

    with no benzodiazepines detected in hair.

    Conclusions: In a large proportion of cases, past use of drugs in addition to those detected in blood,

    was confirmed. Post mortem hair analysis thus gave additional information about the use of

    medicinal drugs in the period before death. In only a very few cases, drugs were detected in blood

    and not in hair.

  • 15

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    O8

    Deposition of diazepam and its metabolites in hair following a single dose of diazepam

    Sys Stybe Johansena, Xin Wanga and Kristian Linneta

    aSection of Forensic Chemistry, Department of Forensic Medicine, University of Copenhagen, Denmark

    Contact information (e-mail(s)): [email protected]

    Introduction Diazepam is one of the most prevalent drug-facilitated crime drugs. Only sporadic data

    are available on hair concentrations of diazepam and some metabolites following a single controlled

    dose. In this study, the deposition of diazepam and its phase I and II metabolites in hair following a

    single dose of diazepam were investigated.

    Materials and methods Eight participants (four women and four men, ages 24–26, Chinese)

    consumed 10 mg diazepam each. Hair was collected one month after exposure, and also two months

    post-exposure from the men and 10 months post-exposure from the women. Diazepam and its

    metabolites were measured after solvent extraction from hair by ultra-high pressure liquid

    chromatography–tandem mass spectrometry (UHPLC–MS/MS).

    Results There were no differences by gender in the amounts of diazepam or metabolites found. The

    proximal segment from 0–2 cm collected one month after administration gave detectable diazepam

    and nordazepam concentrations ranging from 4.0 to 11.8 pg/mg and 9.4 to 24.3 pg/mg, respectively.

    Oxazepam and temazepam traces were found in some segments. In the hair samples collected from

    the four men two months after administration, the highest concentrations of diazepam and

    nordazepam were detected in the 1–3 cm segment corresponding to the time from ingestion with an

    average growth rate of 1 cm/month. The concentrations of both drugs in the 1–3 cm segment

    collected two months post-exposure were similar to that in the 0–2 cm segment collected one

    month after. Diazepam and nordazepam concentrations in the hair collected from the 4 women 10

    months after exposure were near the LOQ, indicating drug loss by personal hygiene and physical

    handling. Oxazepam glucuronide and temazepam glucuronide were not detected in any hair

    segments from the subjects.

    Conclusion Diazepam and nordazepam are detectable at pg/mg level in hair collected one and two

    month after intake of a single dose of diazepam. However, after ten months only traces are found.

    mailto:[email protected]

  • 16

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    O9

    Targeted proteomics of CYP1A2 and CYP3A4 in post-mortem liver tissue

    Jakob Hansena, Anette Daa Fundera, Jørgen Hasselstrøma, Jakob Ross Jornila

    aAarhus University, Department of Forensic Medicine, Bioanalytical Unit

    Contact information (e-mail(s)): [email protected]

    Introduction Members of the cytochrome P450 (CYP) enzyme family metabolize a great number of

    drugs that are responsible for intoxications and drug-related fatalities in forensic settings. Inter-

    individual differences in drug metabolizing capacity and thus susceptibility to adverse drug effects is

    partly based on the expression level and activity of different CYP-isoforms. The activity of specific

    CYP-isoforms is influenced by multiple factors including genetic (polymorphisms and gene-dosage

    effects) and exogenous circumstances such as intake of certain drugs and food ingredients that act

    as both inducers and inhibitors of activity. For the specific CYP-isoforms CYP1A2 and CYP3A4,

    genotyping analyses lack predictive value for enzyme activities and methods for estimating the CYP

    activities in post-mortem materials have not been successful. We have pursued the idea that

    quantification of the protein levels of CYP1A2 and CYP3A4 in post-mortem liver tissue is a valid

    approximation of the corresponding ante-mortem metabolic enzyme capacities.

    The aim of the project was to develop a quantitative method for CYP1A2 and CYP3A4 in hepatic

    tissue and investigate the post-mortem stability of the two CYP-isoforms.

    Materials and methods CYP 1A2 and CYP3A4 proteins were quantified using a targeted proteomics

    approach based on analysis of proteotypic peptides by UPLC-MS/MS. A method for enrichment of

    CYP proteins in microsomal fractions of homogenized post-mortem liver tissue using differential

    centrifugation was established. Peptides generated by trypsin cleavage were separated by reverse

    phase chromatography (C18 column) and detected by multiple-reaction-monitoring. Synthetic stable

    isotopic variants of the target peptides were added and analysed simultaneously with the

    proteotypic CYP peptides to ensure correct identification and accurate quantification. The post-

    mortem stability of CYP enzymes was studied by incubating sample specimens from newly deceased

    persons at different temperatures for up to 7 days. CYP1A2 and CYP3A4 quantification data from

    these stability samples will be presented and discussed.

    Conclusion Post-mortem CYP quantitation may potentially develop into a valuable tool for forensic

    toxicological interpretation by disclosing possible pharmacokinetic causes of low or high drug

    concentrations.

  • 17

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    O10

    In vitro metabolism studies on new designer benzodiazepines

    Carolina Noblea, Niels Bjerre Holma, Sys Stybe Johansena and Kristian Linneta

    aUniversity of Copenhagen, Faculty of Health and Medical Sciences, Dept. of Forensic Medicine, Section of Forensic

    Chemistry

    Contact information (e-mail(s)): [email protected]

    Introduction Designer benzodiazepines are new psychoactive substances recently introduced in the

    illegal drug market. Little is known about metabolism of this group of substances so far.

    Materials and methods In this study, in vitro metabolism of two designer benzodiazepines,

    flubromazolam and clonazolam, was investigated in NADPH-fortified pooled human liver

    microsomes (HLM) and baculovirus-expressed cytochrome CYP-enzymes: CYP1A2, 2A6, 2B6, 2D6,

    2C8, 2C9, 2C18, 2C19, 2E1, 3A4 and 3A5, followed by inhibitory reactions in HLM with 1 and 5 µM

    ketoconazole (CYP3A4/5 inhibitor), 5 µM sulfaphenazole (CYP2C9 inhibitor), 5 µM nootkatone

    (CYP2C19 inhibitor), and 5 µM quinidine (CYP2D6 inhibitor). The parent compound and its

    metabolites were detected by LC-MS on a high-resolution Q-Exactive mass spectrometer, with

    positive electrospray ionization (ESI+) in data-dependent acquisition mode (DDA). Metabolic

    pathways for both compounds in HLM included hydroxylation, and reduction of the nitro group for

    clonazolam.

    Results Reaction phenotyping with CYP-enzymes showed that monohydroxylated metabolites for

    both compounds were primarily produced by CYP3A4 and 3A5. This fact was further supported in

    incubations with ketoconazole in HLM. Flubromazolam was also further metabolized to dihydroxy-

    flubromazolam only by CYP3A4. The reduction of the nitro group of clonazolam to yield the primary

    amine was detected after incubation with CYP2D6, while for CYP3A4 and 2C19 a combination of

    hydroxylation and reduction of the nitro group was observed. Interestingly, formation of this

    metabolite was not observed in HLM. CYP3A4 metabolized clonazolam to monohydroxy-clonazolam

    at the first stage of the reaction (0-60 minutes) and after 120 minutes to monohydroxyamine-

    clonazolam. For CYP2C19, however, only monohydroxyamine-clonazolam was detected after 120

    minutes of incubation. No glucuronides were identified in HLM with the cofactor UDPGA for neither

    of the two drugs, even with the addition of NADPH to produce phase-I metabolites previously

    described. In addition, we identified in vivo metabolites for both compounds in different forensic

    cases and corresponded to those formed in vitro.

    mailto:[email protected]

  • 18

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    O11

    Metabolic profiling using retrospective UPLC-HR-TOF-MS data from forensic toxicology screenings

    Kirstine Lykke Nielsena, Rasmus Telvinga, Mette Findal Andreasena, Jørgen Hasselstrøma, Mogens

    Johannsena

    aDept. of Forensic Medicine, Section for Forensic Chemistry, Aarhus University, Palle Juul-Jensens Boulevard 99, DK-8200

    Aarhus N, Denmark

    Contact information (e-mail(s)): [email protected]

    Introduction Whole blood samples collected by the Danish police from drivers suspected driving

    under the influence of drugs are routinely screened by UPLC-HR-TOF-MS to determine the nature of

    potential drugs.

    Materials and methods Data collected within a two-year period was used for metabolic profiling

    (metabolomics) to evaluate the drug metabolism of 3,4-methylenedioxymethamphetamine (MDMA,

    “Ecstasy”). Metabolomics is an unbiased, untargeted, and very comprehensive method to detect

    changes of low molecular weight metabolites in biological samples in relation to various exposures

    and diseases; thus, it may be useful to profile drug metabolism, mechanism and toxicology.

    Metabolomics usually requires a very controlled setup to minimize biological and external

    confounders to extract useful information. However, the use of such retrospective data involves a

    very heterogeneous population with different concentrations of MDMA/kg blood weight, as well as

    unknown information about amount and time of administration in relation to blood sampling.

    Results Collection of data covering two years may additionally introduce variation from sample

    handling and analysis. Despite of this, it was found possible to extract meaningful information.

    Various statistical methods were tested and their predictability was validated by the positive

    identification of MDMA blood metabolites. In addition, endogenous metabolites that may be related

    to energy metabolism, the serotonergic syndrome, and drug induced neurotoxicity could be

    identified.

    Conclusion The use of retrospective UPLC-HR-TOFMS forensic data is a potential new approach for

    identifying changes in human drug metabolism and endogenous biomarkers related to licit and illicit

    drug administration and toxicology, especially in relation to new designer drugs.

  • 19

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    O12

    Ethanol elimination at low concentrations in drunk drivers

    G. Høisetha, E. Wiika, L. Kristoffersena, J. Mørlanda

    aNorwegian Institute of Public Health, Division of Forensic Medicine

    Contact information (e-mail(s)): [email protected]

    Introduction For ethanol, the elimination curve change from apparent zero to first order kinetics at

    falling blood alcohol concentrations (BACs). This is less studied than elimination at higher BACs, and

    knowledge about this low BAC elimination is especially missing in drunk drivers. The aim of this study

    was to investigate the point at which elimination rates turns from zero to first order kinetics and the

    exact elimination rates at the very low BAC intervals in this population with a high frequency of

    heavy drinkers.

    Materials and methods Two consecutively collected samples from suspected drunk drivers were

    used. All samples were analysed by two headspace gas chromatography flame ionisation detector

    methods (limit of quantification=0.04 g/kg). The elimination rates at BACs below 0.25 g/kg (study

    group, n=175) was studied in detail, and compared to the elimination rates in a moderate BAC

    reference group (n=789) as well as a high BAC reference group (n=4435).

    Results There were no differences in age, gender and driving’s occurring during the night-time

    between the study group and the reference groups. The elimination rates were stable at 0.18-0.19

    g/kg/h from a BAC of 4.0 g/kg and until BAC in the first blood sample fell below 0.19 g/kg. At BACs

    below 0.19 g/kg, the mean elimination rate gradually declined from 0.163 g/kg/h to the lowest

    elimination rate of 0.083 g/kg/h. There was no relation between the concentration of ethanol and

    elimination rate at BACs above 0.19 g/kg (Pearson´s r=0.035, p=0.3), but there was a strong relation

    between concentration of ethanol and elimination rate at BACs below 0.19 g/kg (Pearson´s r=0.56,

    p

  • 20

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    O13

    Post-mortem levels and tissue distribution of codeine, codeine-6-glucuronide, norcodeine,

    morphine and morphine glucuronides in a series of codeine-related deaths

    Joachim Frosta,b, Trine Nordgård Løkkena, Arne Hellanda,b, Ivar Skjåk Nordruma,c, Lars Slørdala,b

    aDepartment of Laboratory Medicine, Children’s and Women’s Health, Norwegian University of Science and Technology

    (NTNU), Trondheim, Norway bDepartment of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway

    cDepartment of Pathology and Medical Genetics, St. Olav University Hospital, Trondheim, Norway

    Contact information (e-mail(s)): [email protected]

    Introduction The toxicodynamics and, to a lesser degree, toxicokinetics of the widely used opiate

    codeine remain a matter of controversy. We present levels and tissue distribution of codeine,

    codeine-6-glucuronide (C6G), norcodeine, morphine and the morphine metabolites morphine-3-

    glucuronide (M3G) and morphine-6-glucuronide (M6G) in post-mortem blood, vitreous fluid, muscle,

    and fat and brain tissue in a series of 23 codeine-related fatalities. CYP2D6 genotype is also

    determined and taken into account.

    Materials and methods Quantification was performed with a validated SPE-LC-MS method. The

    series comprise 19 deaths (83%) attributed to mixed drug intoxication, 4 deaths (17%) attributed to

    other causes of death, and no cases of unambiguous mono-intoxication with codeine. The typical

    peripheral blood concentration pattern in individual cases was

    C6G>>codeine>>norcodeine>morphine, and M3G>M6G>morphine. In matrices other than blood,

    the concentration pattern was similar, although in a less systematic fashion. Measured

    concentrations were generally lower in matrices other than blood, especially in brain and fat, and in

    particular for the glucuronides (C6G, M3G and M6G) and, to some extent, morphine. In brain tissue,

    the presumed active moieties morphine and M6G were both below the LLOQ (0.0080 mg/L and

    0.058 mg/L, respectively) in a majority of cases.

    Conclusion In general, there was a large variability in both measured concentrations and calculated

    blood/tissue concentration ratios. There was also a large variability in calculated ratios of morphine

    to codeine, C6G to codeine and norcodeine to codeine in all matrices, and CYP2D6 genotype was not

    a reliable predictor of these ratios. The different blood/tissue concentration ratios showed no

    systematic relationship with the post-mortem interval. No coherent degradation or formation

    patterns for codeine, morphine, M3G and M6G were observed upon reanalysis in peripheral blood

    after storage.

    Keywords: Forensic toxicology; codeine; toxicity; post-mortem; tissue distribution

    mailto:[email protected]

  • 21

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    O14

    Distribution of QT-prolonging drugs and metabolites between cardiac tissue and femoral blood in

    a psychiatric population

    Christian Reuss Mikkelsena, Jakob Ross Jornila, Ljubica Vukelic Andersena, Jytte Bannerb, Jørgen Bo

    Hasselstrøma

    aDepartment of Forensic Medicine, Aarhus University, DK-8200, Denmark

    bDepartment of Forensic Medicine, University of Copenhagen, DK-2100, Denmark

    Contact information (e-mail(s)): [email protected]

    Introduction The Danish forensic autopsy-based prospective study, named SURVIVE, aims at

    elucidating the causes of the increased mortality and morbidity among mentally ill patients.

    Mentally ill patients are a heavily medicated group, and many of these drugs have been found to

    prolong the QT interval of the ECG. This can lead to the ventricular arrhythmia condition Torsades de

    Pointes which can further lead to sudden cardiac death. In forensic post-mortem toxicology, blood

    concentrations are usually used for estimating a possible death by cardiac arrhythmia. However,

    animal studies and post-mortem case studies have shown that some QT-prolonging drugs (QTD) can

    be found in higher concentration in cardiac tissue when compared to peripheral blood.

    The aim of this project is to characterize the distribution of seven frequently used QTD and their

    metabolites in cardiac tissue and femoral blood to investigate, if the cardiac tissue concentration

    could be a tool for estimating cardiac arrhythmia as a potential cause of death.

    Materials and methods Among the 500 cases included in SURVIVE, cases with at least one of QTD

    reported was selected for this project. A protein precipitation method was used to extract the QTD

    from cardiac homogenate and femoral whole blood. Extracts were analysed on a UPLC-MS/MS.

    Demographic, physiological and forensic results were obtained from police, toxicology and autopsy

    reports for the descriptive analysis.

    211 cases were included in this project, 121 male and 90 female. The compound concentrations in

    whole blood and cardiac tissue were found to be statistically correlated (p0.8), one strong correlated (R^2=0.76) and one moderate correlated

    (R^2= 0.62). Across all 14 compounds the heart-to-blood ratio (HB-ratio) ranged from 0.093 to 43

    and the median HB-ratio ranged from 1.6 to 14. Each compound showed a high variance in HB-ratio

    between cases which was addressed statistically. Only age showed to be statistically significant in

    explaining the high HB-ratio variance of each compound. No difference in HB-ratios was detected

    due to extended post-mortem interval.

    Conclusion In this project, we present the distribution of frequent used QTD’s in the SURVIVE

    population between cardiac tissue and femoral blood.

    mailto:[email protected]

  • 22

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    O15

    Comparison of antidepressiva concentrations in different post mortem media

    Åse Marit Leere Øiestada, Ritva Karinena, Sidsel Rogdea, Kari Beate Boye Eldora, Gerd Wenche

    Brochmanna, Marianne Arnestada, Elisabeth Leere Øiestada, Mariana Dadalto Peresa, Lena

    Kristoffersena, and Vigdis Vindenesa

    aNorwegian Institute of Public Health, Domain for Forensic Sciences, Oslo, Norway

    Contact information (e-mail(s)): [email protected]

    Introduction Analyses of concentrations of different compounds in alternative media to blood or

    urine can improve the understanding of the ante mortem concentrations. In Norway, alternative

    media are mostly used when blood and urine are not available. Several studies comparing different

    media can be found in the literature, but for many compounds the knowledge available for

    interpretation of the results is sparse at best, thus making interpretation difficult. More studies are

    therefore needed, and we have initiated a study aiming to compare concentrations in six different

    media; i.e. peripheral blood, cardiac blood, pericardial fluid, vitreous humour, and two different

    muscles – m vastus lateralis and m psoas. We wish to compare concentrations for a large number of

    drugs and medicinal products in different sampling media, collected in connection with medicolegal

    autopsies.

    Aim The aim of the project is to study how other media than blood/urine can be of use in potential

    intoxication deaths, accidents, and when the deceased’s treatment compliance is questioned.

    Materials and methods So far we have included almost 160 forensic autopsy cases in which intake

    of drugs were suspected. All six media were collected on the same day and were analysed using

    validated GC-MS, LC-MS or UHPLC-MS/MS methods. Care was taken to analyse all media from each

    case on the same series to minimise differences in concentrations due to experimental factors.

    Result We here present results from cases where antidepressants were found.

  • 23

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    O16

    Testosterone levels in forensic cases compared to testosterone levels in long-acting replacement

    therapy with intramuscular testosterone undecanoate

    Yvonne Looda, Bertil Ekmanb, Jeanette Wahlbergb, Johan Ahlnera

    aNational Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Artillerigatan 12, S-587 58

    Linköping, Sweden and Department of Medical and Health Sciences, Linköping University, S-581 85 Linköping, Sweden. bDepartment of Endocrinology and Department of Medical and Health Sciences, Linköping University, S-581 85 Linköping,

    Sweden.

    Contact information (e-mail(s)): [email protected]

    Introduction Testosterone is the most important endogenous anabolic androgenic steroid (AAS) in

    men and next to nandrolone the most frequently abused AAS. The use of AAS is prohibited in

    Sweden since 1999. Testosterone is therapeutically used in the treatment of hypogonadism in men

    and in cross-sex hormone treatment of biological female transsexual individuals to develop and

    maintain male secondary sex characteristics. Determination of AAS in forensic cases and doping

    controls is mainly performed in urine and detection of exogenous testosterone administration is

    complex to discriminate from the state of normality or testosterone levels achieved by conventional

    replacement therapy.

    Aim To study urinary testosterone levels detected in forensic cases comparing to testosterone levels

    in standard treatment with testosterone undecanoate.

    Subjects Forensic cases (n=1155), males with hypogonadism (n=23) and transsexuals with male

    identity (n=15) at the Department of Endocrinology in Linköping and a healthy control group of men

    (n=32) were investigated.

    Methods A national forensic database was used to retrieve toxicological analytical results. Peak and

    trough values of urinary testosterone were measured during testosterone treatment by GC-MS.

    Results Urinary testosterone were by mean significantly higher in the forensic cases (380 ± 397

    ng/mg creatinine) compared to the patient group (62 ± 60 ng/mg creatinine) and controls (33 ± 26

    ng/mg creatinine). The mean T/E ratio was 53 in the forensic cases, 24 in the patients and 1.1 in the

    controls. Peak urinary testosterone, 7-14 days after injection, (1.4-548 ng/mg creatinine) were

    significantly lower compared to the concentrations measured in the forensic cases (10.4-3620 ng/mg

    creatinine). No significant differences were found in trough testosterone levels in treated patients

    comparing to controls.

    Conclusion It seems reliable to discriminate between abuse of testosterone and conventional

    replacement therapy by the significantly higher urinary testosterone concentrations achieved after

    illegal testosterone administration.

  • 24

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    O17

    Reference values of Lithium in post-mortem blood

    Carl Söderberg, Emma Wernvik, Anna Jönsson, Henrik Druid

    National Board of Forensic Medicine, Linköping, Sweden

    Contact information (e-mail(s)): [email protected]

    Introduction The main recipients of lithium, people diagnosed with bipolar disorder, show an

    increased mortality in both natural and unnatural causes of death. Based on international data

    persons diagnosed with bipolar disorder comprise 2.3-9.6 % of all suicidal deaths. In cases of suicide

    among those suffering from bipolar disorder, 17-53 % are due to fatal intoxications. Diagnosing fatal

    intoxications is often challenging in the forensic pathological setting, particularly when the reference

    information needed to evaluate the concentration of a drug is lacking or scarce.

    The aim of this study was to establish post-mortem femoral blood reference concentrations of

    lithium, providing both fatal and “normal” concentrations.

    Materials and methods In Sweden, forensic autopsies are performed in unnatural and obscure

    deaths. This study included all autopsies, in which lithium was found during 1992-2010. Lithium was

    not included in the regular drug screen, but analysed upon request using flame photometry, ion-

    selective electrode detection or atomic absorption spectrophotometry. Each case was evaluated

    according to an established strategy, with strict inclusion and exclusion criteria followed by a multi-

    observer manual review. Included cases were classified as single intoxications (Group A), multi drug

    intoxications (Group B) or control (Group C). The control group only included cases where death by

    intoxication and ante-mortem incapacitation by drugs were ruled out.

    Results During the study period, toxicological analysis of femoral blood samples was performed in

    93,623 autopsies. Lithium was found in 124 (< 1 %) of these. After application of inclusion and

    exclusion criteria and the subsequent manual review, 21 cases were included in the study (Group A,

    n=4; Group B, n=7; Group C, n=10). The femoral blood lithium concentrations in Group A (median

    2.69 mmol/l) and Group B (median 2.10 mmol/l) were significantly different (p=0.01) compared to

    Group C (median 0.2 mmol/l). There were, however no statistically significant difference between

    the concentrations in Group A and Group B.

    Conclusion Although a relatively small number of cases met the inclusion criteria in this study, we

    believe that the presented post-mortem concentrations may be used as a reference when

    interpreting toxicological results involving lithium.

    mailto:[email protected]

  • 25

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    O18

    Beta-hydroxybutyrate and the post mortem diagnosis of ketoacidosis

    Elli Tyrkköa, Anna Jönssona, Robert Kronstranda

    aThe National Board of Forensic Medicine, Linköping, Sweden

    Contact information (e-mail(s)): [email protected]

    Introduction Ketoacidosis, resulting from increased blood beta-oxidative ketone bodies caused by

    alcoholism (alcoholic ketoacidosis, AKA) or diabetes (diabetic ketoacidosis, DKA), is a pathological

    condition that features in many fatalities. The analyses of beta-hydroxybutyrate (BHB), acetone, and

    glucose are essential for identification and differentiation between AKA, DKA and hyperosmolar

    hyperglycaemic state (HHS). The analysis of BHB in blood by GC-MS was introduced in 2013 at the

    laboratory of forensic toxicology in Linköping, Sweden. This study aims at evaluating how the

    analysis of BHB assists in identification of the conditions causing ketoacidosis.

    Materials and methods In the Swedish forensic toxicology and pathology database we identified all

    cases including a BHB analysis, the term “acidosis”, and the ICD9 codes 250C (diabetes with coma)

    and/or 276C (disorders in acid-base balance), for two time periods, 2012-2013 and 2014-2015. The

    AKA, DKA and HHS cases were identified and scrutinized.

    Results The total number of identified cases was 241. The number of cases with AKA as the

    immediate cause of death increased from 5 to 19 between 2012-2013 and 2014-2015. The number

    of BHB analyses increased from 11 to 49 during these time periods. The results from the BHB

    analyses supported the diagnosis of AKA in 18 of the total number of 19 cases reported in 2014-

    2015. The number of DKA cases decreased by 10% (from 93 to 84) between 2012-2013 and 2014-

    2015. The toxicological findings support the diagnosis of HHS in 20 cases in each time period.

    However, HHS was mentioned in the death certificate in only 4 of these 40 cases. The most common

    cause of death assigned in these cases was diabetes with coma.

    Conclusion The study shows that the diagnosis of AKA remarkably benefits from the analysis of BHB.

    Therefore, the analysis of BHB is strongly recommended in cases, where glucose is low and acetone

    is positive in either blood or urine, and there is no other competing cause of death. Analysis of BHB

    also aids in differentiation of DKA from HHS, as acetone might be negative in blood in some cases.

    We also found that HHS is clearly an under-identified condition.

    Keywords beta-hydroxybutyrate, alcoholic ketoacidosis, diabetic ketoacidosis, hyperosmolar

    hyperglycaemic state

  • 26

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    O19

    Deaths attributed to 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (α-PVP)

    Robert Kronstranda

    aNational Board of Forensic Medicine, Linköping, Sweden

    Contact information (e-mail(s)): [email protected]

    Introduction The psychoactive substance 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone or α-PVP emerged

    on the European market around 2011. It is a cathinone without substitutions on the phenyl ring

    structure. The toxidromes commonly encountered after ingestion of cathinones are mainly of

    sympathomimetic and hallucinogenic character with a risk of excited delirium and life-threatening

    cardiovascular effects. Reported severe side-effects from α-PVP are tachycardia, hypertension,

    hyperthermia, and rhabdomyolysis. Since 2011, α-PVP has been a fairly common finding in both

    cases from the living and the dead even after it was scheduled February 1st 2013.

    Materials and methods To investigate the occurrence of acute fatal toxicity of α-PVP a database

    search was performed. All cases found positive for α-PVP between 2011 and 2015 were included.

    The ante-mortem and post mortem findings in cases of fatal intoxication were evaluated.

    Results The search resulted in 641 positive findings in the living and 22 positive findings in autopsy

    cases. There was a steep increase in positive cases with a peak of 221 and 9 cases during 2014. Ten

    of the autopsy cases were signed out as fatal intoxications by the medical examiner. Of these, one

    was unrelated to α-PVP, 7 had α-PVP as contributing, and two had α-PVP as the primary cause of

    death. The first case involved a 43 year old male that after having injected α-PVP was found

    unconscious by a friend. Arriving at hospital he was still unconscious, had tachypnea and was

    shaking. He presented with brain edema, brain haemorrhages and an examination of the brain

    revealed severe anoxic brain injury and life support was stopped one day after arrival. The femoral

    blood concentration of α-PVP was 0.008 µg/g which seem low but can partly be explained by

    metabolism during supportive treatment. The second case was not witnesses and the autopsy

    revealed moderate brain edema, pulmonary congestion, lung emphysema and needle marks. The

    femoral blood concentration of α-PVP was 0.04 µg/g. Among the other deaths one showed signs of

    excited delirium with excitation, confusion, and hyperthermia but died from multiple injuries after a

    fall from a six story building.

    Conclusion In conclusion, among the 22 findings of α-PVP in autopsy cases 10 were intoxications and

    7 had α-PVP as contributing or primary cause of death.

    mailto:[email protected]

  • 27

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    O20

    An increase in fentanyl-related deaths during the winter 2015/2016

    Gunilla Thelandera and Robert Kronstranda

    aThe National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linköping, Sweden

    Contact information (e-mail(s)): [email protected]

    Introduction A sudden increase in fentanyl positive cases prompted us to investigate this further.

    The aim of our study was to show the Swedish situation of fentanyl-related deaths and describe the

    demographics, circumstances, and post mortem findings.

    Material and methods Autopsy cases from 2015 to March 2016 with positive findings of fentanyl

    were reviewed regarding concentrations, cause of death, age, gender, location in Sweden and

    availability of fentanyl in different forms.

    Results We found a significant increase in deaths related to fentanyl from December 2015 and

    onwards. Many of the decedents had a history of drug abuse and several cases indicated frequent

    poly-drug use. Prior to December no more than 5 cases were seen per month 2015 (mean= 3 cases).

    During December we encountered 22 fatal intoxications, in January 2016 there were 16 and in

    February 8 fentanyl deaths. The preliminary figure for March is 9; however cause of death has not

    been assigned to all cases yet. Of these decedents 85 % were male and the median age was 34 years.

    Geographically, the cases were from all regions of the country. During December to February, the

    most common forms of fentanyl were powder, nasal sprays, and tablets even though a few cases of

    transdermal patches were seen. The blood concentrations of fentanyl (December to February)

    revealed; range 0.06-142 ng/g, median 18 ng/g and mean 26 ng/g.

    Conclusion The increased availability of fentanyl has generated a large peak of fentanyl-related

    deaths in Sweden. The data suggest that the fentanyl derived, not from pharmaceutical fentanyl, but

    from illegal sources.

  • 28

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    O21

    Trends in fatal poisonings by prescription drugs in Finland since 2000

    Ilkka Ojanperäa

    aDepartment of Forensic Medicine, University of Helsinki and Forensic Toxicology Unit, National Institute for Health and

    Welfare, Helsinki, Finland

    Contact information (e-mail(s)): [email protected]

    Introduction The present paper reviews the trends in fatal poisonings by prescription drugs in

    Finland during 2000 – 2013.

    Materials and methods The post-mortem toxicology database included for each case the forensic

    pathologist's referral, laboratory analysis results, and information extracted from the death

    certificate issued by forensic pathologist. The prevalences of fatal prescription drug poisonings were

    based on the most important single drug finding in each fatality, as stated in the death certificate.

    Results The number of fatal poisonings due to drugs during the period 2000 – 2013 has varied from

    450 to 600 cases. The annual number of poisonings by antipsychotics has stabilized at 60 cases after

    the withdrawal of promazine that still caused tens of poisonings 2000 – 2003. Quetiapine and

    levomepromazine formed the major part of antipsychotics poisonings in 2013. The annual number

    of antidepressant poisonings averaged 120 cases during 2000 – 2009, but since then the number has

    steadily declined to 80 cases. In 2013, amitriptyline and venlafaxine were the most frequent major

    antidepressant drugs but bupropion was on the increase in 2013 and should be carefully monitored.

    The annual number of poisonings by prescription opioids has steadily increased from 50 to 200 cases

    during 2000 – 2011 and, since then, decreased to 160 cases in 2013. Buprenorphine and tramadol

    formed the major part of opioid poisonings in 2013. The proportion of prescription opioids from all

    drug poisonings was 33% in 2013, as opposed to only 9.5% in 2000. The annual number of

    poisonings by hypnotics and sedatives since 2000 has varied from 40 to 80 cases; being 65 cases in

    2013. Pregabalin was associated with the highest number of poisonings among hypnotics and

    sedatives, with 26 cases in 2013.

    Conclusion When the number of fatal poisonings was divided by the associated sales using the

    number of defined daily doses (summed from years 2005, 2009 and 2013), the following prescription

    drugs possessed the highest risk of fatal poisonings in descending order of risk: methadone,

    dextropropoxyphene, levomepromazine, doxepin, chlorprothixene, oxycodone, amitriptyline,

    trimipramine, tramadol, morphine, bupropion, clomipramine, propranolol, quetiapine, fentanyl,

    codeine, and pregabalin. Buprenorphine was not evaluated because of the frequency of illicit

    trafficking associated with the drug.

  • 29

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    O22

    Re-offending in drug-related crimes in Sweden, 1993 – 2013

    Johan Ahlnera, Anita Holmgrena, A. Wayne Jonesa

    aNational Board of Forensic Medicine and Institution of Medicine and Care, Linköping University, Linköping, Sweden

    Contact information (e-mail(s)): [email protected]

    Introduction The National Laboratory of Forensic Toxicology in Linköping receives annually ~30 000

    suspected cases of illegal drug use along with ~12 500 cases of driving under the influence of drugs.

    Our statistics show that during the period 1993-2013 over 600 000 drug-related cases were

    registered and toxicological analysis of blood and/or urine samples were performed.

    Materials and methods Information about all cases of illegal drug use or driving under the influence

    of drugs were extracted from a national forensic toxicology database (TOXBASE) for scrutiny. The

    database contained a personal identification number, age, and sex of the suspect and results of a

    comprehensive toxicological analysis of blood and urine for licit and illicit drugs.

    Results During the period 1993-2013 around 630 000 cases were registered at our laboratory. We

    found that 80% of those arrested were repeat offenders, that is, the same suspect appeared at least

    once before in the database. We found that 503 260 positive cases belonged to only 88 067 different

    individuals, which makes an average of 5.7 arrests per person. The central stimulant amphetamine

    was the most commonly encountered illicit drug, followed by abuse of cannabis/marijuana. Among

    reoffenders more than 87 % were men. One individual had been arrested 154 times over the 21 year

    study period and in one year he was arrested on 21 occasions. Around 300 different individuals were

    arrested at least 50 times each.

    Conclusion Reoffending frequency was high in people arrested in Sweden for use of illegal drugs or

    driving under the influence of drugs. This probably reflects an increased activity by the police

    authorities and ineffectiveness of the legal sanctions for those convicted of such drug-related

    crimes. Much might be gained by sentencing to a mandatory treatment programme for substance

    abuse disorder rather than monetary fines or short terms of imprisonment.

  • 30

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    O23

    Experiences in an EU project “Strengthening and modernizing the forensic services in Kosovo”

    Ilpo Rasanena

    aNational Institute for Health and Welfare (THL), Helsinki, Finland

    Contact information (e-mail(s)): [email protected]

    Introduction A consortium formed by the National Institute for Health and Welfare (THL) and the

    University of Helsinki implemented an EU funded project “Strengthening and modernizing the

    forensic services in Kosovo” starting in February 2014. Later, the project received a one-year

    extension and will continue until February 2017. The project team consists of a team leader (410

    working days) and a key expert II (220 working days), as well as several short term experts

    implementing the training programme.

    The purpose of the project is to strengthen and modernize the forensic services at the Department

    of Forensic Medicine (DFM) in Pristina by enhancing its technical and administrative capacity.

    Materials and methods The terms of reference of the project were written in the EU Office in

    Kosovo. After the inception period, it was found that the goals of the project were set too high

    compared to the current status of DFM. In the inception report, the project team evaluated the

    current status of DFM and presented the training needs and a proposal for the new equipment

    purchased by the project. These issues were sharpened during the project.

    My main role in the project was to develop the laboratory for toxicology in DFM. The laboratory was

    founded in 2006 by the United Nations when also the new building of DFM was build. The personnel

    of the laboratory consist of a laboratory manager, a chemist and a toxicologist. In 2014, the

    analytical equipment of the laboratory consists of immunoassay (ELISA) equipment, a CO-oximeter,

    an HS-GC and two GC-MS instruments.

    The autopsy rate in Kosovo is very low, being approximately 300-350 cases annually, compared with

    the population of about 1.7 million. The laboratory has received samples from about 250 autopsy

    cases annually. Only qualitative screenings were performed before the project started. My goal was

    to develop new methods and to exploit the quantitative methods used in Helsinki for alcohols,

    carbon monoxide and most common drugs of abuse (opiates, amphetamines, cannabis,

    benzodiazepines and cocaine), as well as for individual therapeutic drugs. However, for example the

    lack of reference standards and the difficulty to purchase them complicated the goal considerably.

    Conclusion Developing the laboratory operation has been challenging, such as many other parts of

    the project as well. I have encountered a multitude of surprises and setbacks during the project that

    I could not imagine take place in the 2000s. All things seem to be more difficult in developing

    countries.

    The training programme has been implemented fairly successfully. The challenges, difficulties and

    major achievements of the project will be discussed.

  • 31

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    Participants

    Johan Ahlner The National Board of Forensic Medicine, Sweden Aðalheiður Dóra Albertsdóttir University of Iceland Ingeborg Amundsen Folkehelseinstituttet, Norway Ljubica Vukelic Andersen Department of Forensic Medicine, Aarhus University, Denmark Nina Zacho Andersen University of Copenhagen, Denmark Mette Findal Andreasen Department of Forensic Medicine, Aarhus University, Denmark Marianne Arnestad Norwegian Institute of Public Health, Norway Liliana Bachs Norwegian Institute of Public Health, Norway Eirin Bakke Norwegian Institute of Public Health, Norway Jesper Berggreen Department of Forensic Medicine, Aarhus University, Denmark Willy Bjørklund Thermo Fisher Scientific, Sweden Jenny Button Chiron / CAS Referensmaterial AB, Norway Søren Dalby Bruker Daltonics, Denmark Petur Dalsgaard University of Copenhagen, Denmark Henrik Druid Rättsmedicinalverket, Norway Anne Dyrdal Waters A/S, Denmark Elin Eliassen Institute of Public Health, Norway Eva Ericsson The National Board of Forensic Medicine, Sweden Tina Eriksen Syddansk University, Denmark Liselotte Frantzen Department of Forensic Medicine, Aarhus University, Denmark Jens Glastrup MSCi ApS, Denmark Per Ole M. Gundersen St. Olavs Hospital, Trondheim University Hospital, Norway Kristin Irene Gaare Institute of Public Health, Norway Solveig Sif Halldorsdottir University of Iceland An-Magritt Haneborg Institute of Public Health, Norway Jakob Hansen Department of Forensic Medicine, Aarhus University, Denmark Tore Hardlei Department of Forensic Medicine, Aarhus University, Denmark Jørgen Bo Hasselstrøm Department of Forensic Medicine, Aarhus University, Denmark Solfrid Hegstad St. Olavs Hospital, Trondheim University Hospital, Norway Niels Bjerre Holm University of Copenhagen, Denmark Gudrun Høiseth Institute of Public Health, Norway Pernilla Haage The National Board of Forensic Medicine, Sweden Gerd Jakobsson The National Board of Forensic Medicine, Sweden Brian Sonne Jensen Department of Forensic Medicine, Aarhus University, Denmark Mogens Johannsen Department of Forensic Medicine, Aarhus University, Denmark Sys Johansen University of Copenhagen, Denmark Unni Johansen Institute of Public Health, Norway Anna Johansson The National Board of Forensic Medicine, Sweden Jakob Ross Jornil Department of Forensic Medicine, Aarhus University, Denmark Martin Josefsson The National Board of Forensic Medicine, Sweden Aino Kankaanpää National Institute for Health and Welfare, Helsinki, Finland Inge Korup Department of Forensic Medicine, Aarhus University, Denmark Robert Kronstrand The National Board of Forensic Medicine, Sweden Fredrik Kugelberg The National Board of Forensic Medicine, Sweden Susan Marie Jøker Lambertsen Department of Forensic Medicine, Aarhus University, Denmark Veronica Horpestad Liane Institute of Public Health, Norway Sofia Lindahl St. Olavs Hospital, Trondheim University Hospital, Norway Lone Lindal University of Southern Denmark

  • 32

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    Christian Lindholst Department of Forensic Medicine, Aarhus University, Denmark Kristian Linnet University of Copenhagen, Denmark Yvonne Lood The National Board of Forensic Medicine, Sweden Samuel Mesihää University of Helsinki, Finland Gerrit J Middelkoop FHI Christian Reuss Mikkelsen Department of Forensic Medicine, Aarhus University, Denmark Sisse Elle Mikkelsen Department of Forensic Medicine, Aarhus University, Denmark Peter Milland Bruker Daltonics, Denmark Christian Brinch Mollerup University of Copenhagen, Denmark Kirstine Lykke Nielsen Department of Forensic Medicine, Aarhus University, Denmark Louise Stride Nielsen Department of Forensic Medicine, Aarhus University, Denmark Gunnel Nilsson The National Board of Forensic Medicine, Sweden Andrea Carolina Noble University of Copenhagen, Denmark Ilkka Ojanperä University of Helsinki, National Institute Health & Welfare, Finland Mads Lundgren Petersen Agilent Technologies, Sweden Emma Rapp The National Board of Forensic Medicine, Sweden Ilpo Rasanen University of Helsinki, National Institute Health & Welfare, Finland Brian Schou Rasmussen University of Copenhagen, Denmark Nina Ringquist The National Board of Forensic Medicine, Sweden Ingrid Rosendal Department of Forensic Medicine, Aarhus University, Denmark Tim Salbert Advanced Chemistry Development Germany GmbH Mette-Lise Simonsen Department of Forensic Medicine, Aarhus University, Denmark Tina Slots Department of Forensic Medicine, Aarhus University, Denmark Dag Helge Strand Institute of Public Health, Norway Lena Ström The National Board of Forensic Medicine, Sweden Eva Sædder Department of Forensic Medicine, Aarhus University, Denmark Carl Söderberg National Board of Forensic Medicine, Sweden Lauri Saastamoinen Sigma-Aldrich subsidiary of Merck, England Helena Tell The National Board of Forensic Medicine, Sweden Rasmus Telving Department of Forensic Medicine, Aarhus University, Denmark Lone Støvring Rattenborg Department of Forensic Medicine, Aarhus University, Denmark Cecilie Thaulow Institute of Public Health, Norway Gunilla Thelander The National Board of Forensic Medicine, Sweden Svava Thordardottir University of Iceland Inga Dahl Sigma-Aldrich subsidiary of Merck, Denmark Elli Tyrkkö The National Board of Forensic Medicine, Sweden Jenni Viinamäki University of Helsinki, Finland Svante Vikingsson Linköping University, Sweden Denise Wallworth Sigma-Aldrich subsidiary of Merck, England Linda Widar Chiron / CAS Referensmaterial AB, Sweden Ariane Wohlfarth The National Board of Forensic Medicine, Sweden Åse Marit Leere Øiestad Institute of Public Health, Norway

  • 33

    AARHUS

    UNIVERSITY

    HEALTH

    DEPARTMENT OF FORENSIC MEDICINE

    Welcome to Trondheim in 2017!

    3rd annual NAFT meeting and general assembly

    De Department of Clinical Pharmacology St. Olavs Hospital - Trondheim University Hospital, Norway


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