Publications
-
Dalaker, Vivian Moe; Bjørnaas, Mari Asphjell; Øiestad, Elisabeth Leere; Brekke, Mette & Vallersnes, Odd Martin
(2026).
Covert administration of drugs in drug facilitated sexual assault: A prospective observational study from Oslo, Norway.
Forensic Science International: Reports.
14.
doi:
10.1016/j.fsir.2026.100489.
Full text in Research Archive
Show summary
Objective
To identify drugs in blood and urine samples from victims of sexual assault suspecting exposure to covert administration of drugs, and compare with substances reported taken by the victim.
Methods
We analyzed forensic blood and urine samples from patients 16 years or older presenting at the Oslo Sexual Assault Centre, Norway, suspecting exposure to covert administration of drugs in relation to the sexual assault. We recorded psychoactive substances reported taken before suspected exposure. Blood samples were analyzed for 64 drugs using ultra-high performance liquid chromatography – tandem mass spectrometry (UHPLC-MS/MS) and an automated enzymatic method for ethanol. Urine samples were analyzed for 39 drugs using liquid chromatography – tandem mass spectrometry (LC-MS/MS), and an additional nine drugs using immunoassay methods.
Results
We included 50 patients, median age 23 years, 49 were women. Median time from suspected exposure to toxicological sampling was 22 h. Drugs not reported taken were found in 17 (34%) patients, combined with drugs reported taken in nine. In 15 patients we only found drugs reported taken. Unreported drugs found in blood were cocaine in three patients, alprazolam in two, methylenedioxymethamphetamine/methylenedioxyamphetamine (MDMA/MDA) in two, tetrahydrocannabinol (THC) in one, and amphetamine in one. Unreported drugs found in urine were cocaine in eleven patients, MDMA/MDA in three, alprazolam in two, codeine in two, cannabis in one, oxazepam in one, amphetamine in one, and zolpidem in one. Gammahydroxybutyrate (GHB) was not detected in either matrix.
Conclusion
Unreported drugs were found in 34% of sexual assault victims suspecting covert administration of drugs.
-
Noreng, Line; Øiestad, Åse Marit Leere; Hansen, Frederik Andre; Røberg-Larsen, Hanne; Wilson, Steven Ray Haakon & Øiestad, Elisabeth Leere
(2026).
Toward Sustainable Clinical Analysis: Benchmarking Plastic Use in LC–MS Sample Preparation – Exemplified by Ketamine Analogues in Whole Blood.
Analytical Chemistry.
ISSN 0003-2700.
98(16),
p. 11899–11909.
doi:
10.1021/acs.analchem.5c08225.
Full text in Research Archive
-
Jamt, Ragnhild Elén Gjulem; Gjerde, Hallvard; Clausen, Grethe Brennhovd; Bache-Andreassen, Lihn & Øiestad, Elisabeth Leere
(2025).
Evaluation of DrugWipe® 6S with the WipeAlyser® reader for drug screening of drivers.
Journal of Analytical Toxicology.
ISSN 0146-4760.
49(7),
p. 442–449.
doi:
10.1093/jat/bkaf028.
Full text in Research Archive
-
Landmark, Cecilie Johannessen; Sætre, Johan; Gottås, André; Wolden, Martha; M`Quaele, Tao & Kjeldsen, Signe Flood
[Show all 12 contributors for this article]
(2025).
Pharmacokinetic variability and use of therapeutic drug monitoring of cannabidiol in patients with refractory epilepsy.
Epilepsia.
ISSN 0013-9580.
66(5),
p. 1477–1491.
doi:
10.1111/epi.18284.
Full text in Research Archive
Show summary
Objective: Cannabidiol (CBD) (Epidyolex) is a new antiseizure medication (ASM) for rare and severe epileptic syndromes. We aimed to investigate the pharmacokinetic variability of CBD to elucidate relationships between doses, serum concentrations, metabolites, and biochemical markers of toxicity by using therapeutic drug monitoring (TDM) data.
Methods: Data on serum concentrations of all ASMs, CBD, and the active metabolite 7-hydroxy-cannabidiol (7-OH-CBD) were collected (January 2022 to June 2023) at the Section for Clinical Pharmacology, National Centre for Epilepsy, Oslo University Hospital.
Results: Data from 52 patients were included: 122 serum concentration measurements (1-7 per patient); 48% female, mean age 23 (range 3-55) years. At maintenance (n = 34), the mean daily dose was 535 (SD 224) mg, that is, 10.03 (standard deviation [SD] .49) mg/kg/day, serum concentration .26 (SD .14) for CBD and .13 (SD .10) μmol/L for 7-OH-CBD. Reference ranges of .15-.50 μmol/L for CBD and .04-.25 μmol/L for 7-OH-CBD are proposed, which included 80% of measurements. There was a linear correlation between CBD dose to concentration and CBD to CBD-7-OH concentrations (r2 = .39 and .38) (p < .05). The hepatic marker alanine aminotransferase (ALT) increased on average 37%, demonstrating a moderate effect on liver function. Intra-individual coefficients of variation (CVs) were 32% (SD 17) for CBD and 48% (SD 24) for 7-OH-CBD (n = 15, ≥3 measurements). Twenty different ASMs were used: clobazam (n = 24), valproate (n = 17), and stiripentol (n = 8) were most common. The mean concentration ratio of desmethyl-clobazam/clobazam increased by 140% (7.29-17.5; p < .05) but was variable, pointing to enzyme inhibition by CBD.
Significance: This observational study with TDM data revealed extensive pharmacokinetic variability of CBD in patients with refractory epilepsy. The results demonstrate the need for close follow-up and use of TDM, including biochemical markers of toxicity, for individualized treatment with CBD.
-
Fabris, André L.; Hansen, Frederik Andre; Yonamine, Mauricio; Pedersen-Bjergaard, Stig & Øiestad, Elisabeth Leere
(2024).
An efficient and green method for the analysis of synthetic cathinones in whole blood using 96-well electromembrane extraction and LC-MS/MS.
Sustainable Chemistry and Pharmacy.
38,
p. 1–12.
doi:
10.1016/j.scp.2024.101494.
Full text in Research Archive
Show summary
Electromembrane extraction (EME) is a miniaturized technique in which charged molecules are extracted from biological samples, through a porous membrane, into an acceptor solution. This process occurs in the presence of an electric field that enables increased analyte recovery in short extraction times. Studies are being carried out to establish recommended extraction conditions for different groups of compounds based on their physicochemical properties. In this work, pre-established generic liquid membranes for the extraction of basic compounds were tested using synthetic cathinones within a wide log P range as basic model analytes. First, recommended organic solvents for the chosen analytes were evaluated in terms of recovery. The best candidates were included in an optimization study with other relevant EME conditions (voltage, extraction time, and agitation rate). All analyses were performed using a UPLC-MS/MS with the multiple reaction monitoring mode. 2-Undecanone was chosen as the liquid membrane providing the best extraction efficiency in combination with 40 V, 35 min, and 725 rpm. Validation showed r2 > 0.99 in the 1–500 ng/mL range, accuracy of ±12%, imprecision of ≤19%, 1 ng/mL as limit of quantitation, 0.1–0.5 ng/mL as limit of detection, matrix effect 97–118%, and recovery 63–110%. Among the generic liquid membranes studied in this work, 2-Undecanone was the best choice for the target basic analytes. High recoveries and low matrix effects were achieved, thus demonstrating the applicability of recommended generic liquid membranes in the 96-well plate setup and with whole blood samples. Our findings contribute to further establishing EME as an actual sample preparation technique for routine analyses that could be further explored in a commercial format.
-
Schüller, Maria; Bergh, Marianne Skov-Skov; Pedersen-Bjergaard, Stig & Øiestad, Elisabeth Leere
(2024).
Electromembrane extraction of drugs of abuse and prescription drugs from micropulverized hair.
Journal of Analytical Toxicology.
ISSN 0146-4760.
48(7),
p. 489–498.
doi:
10.1093/jat/bkae051.
Full text in Research Archive
Show summary
Hair analysis can provide chronological insights into past drug use for months to years after drug administration. In comparison to analyses from other biological matrices, such as blood and urine, sample pretreatment is often tedious and not environmental friendly. In this study, we present a more environmental friendly approach to hair analysis using micropulverized hair and electromembrane extraction for the efficient extraction of 15 drugs of abuse, prescription drugs, and metabolites from hair. The optimized extraction method, involving micropulverization, demonstrated comparable yields to the standard approach of cutting and overnight incubation. A 15-min extraction method using a commercial electromembrane extraction prototype was developed and validated according to forensic guidelines, using only 10 µL of organic solvent per sample. The final method, employing HPLC–MS–MS with a biphenyl column, exhibited good linearity, precision, and sensitivity. An AgreePrep assessment comparing the environmental impact of our method with the standard routine method, involving overnight incubation and conventional liquid–liquid extraction, was conducted. This is the first time micropulverized hair has been subjected to electromembrane extraction.
-
Bakke, Eirin; Nilsen, Mariann; Strand, Dag Helge; Øiestad, Elisabeth Leere & Høiseth, Gudrun
(2024).
Enantiomer-specific analysis of amphetamine in urine, oral fluid and blood.
Journal of Analytical Toxicology.
ISSN 0146-4760.
48(5),
p. 254–262.
doi:
10.1093/jat/bkae038.
Full text in Research Archive
Show summary
Illegal amphetamine is usually composed of a racemic mixture of the two enantiomers (S)- and (R)-amphetamine. However, when amphetamine is used in medical treatment, the more potent (S)-amphetamine enantiomer is used. Enantiomer-specific analysis of (S)- and (R)-amphetamine is therefore used to separate legal medical use from illegal recreational use. The aim of the present study was to describe our experience with enantiomer-specific analysis of amphetamine in urine and oral fluid, as well as blood, and examine whether the distribution of the two enantiomers seems to be the same in different matrices. We investigated 1,722 urine samples and 1,977 oral fluid samples from prison inmates, and 652 blood samples from suspected drugged drivers, where prescription of amphetamine was reported. Analyses were performed using ultra high performance liquid chromatography–tandem mass spectrometry (UHPLC–MS-MS). The enantiomer separation was achieved by using a chiral column, and results from the method validation are reported. Samples containing <60% (S)-amphetamine were interpreted as representing illegal use of amphetamine. The distribution of the two enantiomers was compared between different matrices. In urine and oral fluid, the mean amount of (S)-amphetamine was 45.2 and 43.7%, respectively, while in blood, the mean amount of (S)-amphetamine was 45.8%. There was no statistically significant difference in the amount of (S)-amphetamine between urine and oral fluid samples and between urine and blood samples, but the difference was significant in blood compared to oral fluid samples (P < 0.001). Comparison of urine and oral fluid between similar populations indicated that enantiomers of amphetamine can be interpreted in the same way, although marginally higher amounts of (R)-amphetamine may occur in oral fluid. Oral fluid, having several advantages, especially during collection, could be a preferred matrix in testing for illegal amphetamine intake in users of medical amphetamine.
-
Dalaker, Vivian Moe; Furuhaugen, Håvard; Brekke, Mette; Bjørnaas, Mari Asphjell; Krpo, Maja & Øiestad, Elisabeth Leere
[Show all 7 contributors for this article]
(2024).
Drugs in blood and urine samples from victims of suspected exposure to drink spiking: A prospective observational study from Oslo, Norway.
PLOS ONE.
19(7),
p. 1–14.
doi:
10.1371/journal.pone.0306191.
Full text in Research Archive
Show summary
Objective People regularly contact emergency medicine services concerned that they have been exposed to drink spiking, i.e., exposure to drugs without their knowledge or permission. We identified drugs in blood and urine samples from patients suspecting exposure to drink spiking, with special consideration for drugs not reported taken by the patient (unreported drugs). Methods From September 2018 to May 2019, we collected blood and urine samples from patients 16 years or older presenting at an emergency clinic in Oslo, Norway, within 48 hours of suspected exposure to drink spiking. We also collected information on ethanol ingestion and drugs taken. Blood samples were analyzed for 20 classical recreational drugs using ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) and an automated enzymatic method for ethanol. Urine samples were analyzed using immunoassay methods and a specific gas chromatography mass spectrometry (GCMS) method for gammahydroxybutyrate (GHB). Results From 100 included patients (median age 24 years, 62 females), we collected 100 blood samples and 72 urine samples. Median time since exposure was 5 hours. Unreported drugs were found in 15 patients. Unreported drugs in the blood samples were clonazepam in 3, methylenedioxymethamphetamine (MDMA) in 3, amphetamine in 2, tetrahydrocannabinol (THC) in 2, tramadol in 1, cocaine in 1, and methamphetamine in 1. Unreported drugs in the urine samples were cocaine in 5, amphetamine in 4, ecstasy in 3, and cannabis in 2. Ethanol was found in 69 patients, all reporting ethanol ingestion. Median blood ethanol concentration was higher in patients with no unreported drugs detected, 1.00‰ (interquartile range (IQR) 0–1.52) vs. 0‰ (IQR 0–0.46) (p<0.001). GHB was not detected. Conclusion Unreported drugs, possibly used for drink spiking, were found in 15% of patients. Blood ethanol concentration was higher when no unreported drugs were found. GHB was not detected in any patient.
-
-
Schüller, Maria; Lucic, Ivana; Øiestad, Åse Marit Leere; Pedersen-Bjergaard, Stig & Øiestad, Elisabeth Leere
(2023).
High-throughput quantification of emerging “nitazene” benzimidazole opioid analogs by microextraction and UHPLC–MS-MS.
Journal of Analytical Toxicology.
ISSN 0146-4760.
47(9),
p. 787–796.
doi:
10.1093/jat/bkad071.
Full text in Research Archive
Show summary
Abstract Benzimidazole opioids, often referred to as nitazenes, represent a subgroup of new psychoactive substances with a recent increase in fatal overdoses in the USA and Europe. With a variety of analogs emerging on the illicit drug market, forensic laboratories are challenged to identify these potent drugs. We here present a simple quantitative approach for the determination of nine nitazene analogs, namely, clonitazene, etodesnitazene, etonitazene, etonitazepyne, flunitazene, isotonitazene, metodesnitazene, metonitazene and protonitazene in whole blood using liquid-phase microextraction and electromembrane extraction in a 96-well format and liquid chromatography–tandem mass spectrometry. Green and efficient sample preparation was accomplished by liquid-phase microextraction in a 96-well format and resulted in high extraction yields for all analytes (&gt;81%). Here, blood diluted with buffer (1:1, %v) was extracted from a donor compartment across a thin organic liquid membrane and into an aqueous acceptor solution. The acceptor solution was collected and directly injected into the analysis platform. Chromatographic separation was accomplished with a biphenyl column, allowing for a baseline separation of the structural isomers isotonitazene and protonitazene before detection by multiple reaction monitoring. Validation was performed according to Scientific Working Group of Forensic Toxicology guidelines. The calibration range was from 0.5 to 50 nM (except for protonitazene and clonitazene from 0.1 nM) with good linearity and limits of detection down to 0.01 nM. An AGREEprep assessment was performed to evaluate sample preparation greenness, with a final score of 0.71. Nitazenes represent a current threat to public health, and analytical methods that cover a wide range of these analogs are limited. Here, the described method may assist in the detection of nitazenes in whole blood and prevent these substances from being missed in postmortem investigations.
-
Schüller, Maria; McQuade, Tao Angell-Petersen; Bergh, Marianne Skov-Skov; Pedersen-Bjergaard, Stig & Øiestad, Elisabeth Leere
(2023).
Determination of tryptamine analogs in whole blood by 96-well electromembrane extraction and UHPLC-MS/MS.
Talanta Open.
7.
doi:
10.1016/j.talo.2022.100171.
Full text in Research Archive
-
-
Skaalvik, Tonje Gottenberg; Zhou, Chen; Øiestad, Elisabeth Leere; Hegstad, Solfrid; Trones, Roger & Pedersen-Bjergaard, Stig
(2023).
Conductive vial electromembrane extraction of opioids from oral fluid.
Analytical and Bioanalytical Chemistry.
ISSN 1618-2642.
415,
p. 5323–5335.
doi:
10.1007/s00216-023-04807-3.
Full text in Research Archive
Show summary
The use of oral fluid as sample matrix has gained significance in the analysis of drugs of abuse due to its non-invasive nature. In this study, the 13 opioids morphine, oxycodone, codeine, O-desmethyl tramadol, ethylmorphine, tramadol, pethidine, ketobemidone, buprenorphine, fentanyl, cyclopropylfentanyl, etonitazepyne, and methadone were extracted from oral fluid using electromembrane extraction based on conductive vials prior to analysis with ultra-high performance liquid chromatography–tandem mass spectrometry. Oral fluid was collected using Quantisal collection kits. By applying voltage, target analytes were extracted from oral fluid samples diluted with 0.1% formic acid, across a liquid membrane and into a 300 μL 0.1% (v/v) formic acid solution. The liquid membrane comprised 8 μL membrane solvent immobilized in the pores of a flat porous polypropylene membrane. The membrane solvent was a mixture of 6-methylcoumarin, thymol, and 2-nitrophenyloctyl ether. The composition of the membrane solvent was found to be the most important parameter to achieve simultaneous extraction of all target opioids, which had predicted log P values in the range from 0.7 to 5.0. The method was validated in accordance to the guidelines by the European Medical Agency with satisfactory results. Intra- and inter-day precision and bias were within guideline limits of ± 15% for 12 of 13 compounds. Extraction recoveries ranged from 39 to 104% (CV ≤ 23%). Internal standard normalized matrix effects were in the range from 88 to 103% (CV ≤ 5%). Quantitative results of authentic oral fluid samples were in accordance with a routine screening method, and external quality control samples for both hydrophilic and lipophilic compounds were within acceptable limits.
-
Skaalvik, Tonje Gottenberg; Øiestad, Elisabeth Leere; Pedersen-Bjergaard, Stig & Hegstad, Solfrid
(2023).
Determination of amphetamine enantiomers in urine by conductive vial electromembrane extraction and ultra-high performance supercritical fluid chromatography tandem mass spectrometry.
Drug Testing and Analysis.
ISSN 1942-7603.
15,
p. 909–918.
doi:
10.1002/dta.3487.
Full text in Research Archive
Show summary
Separation and quantification of amphetamine enantiomers are commonly used to distinguish between consumption of prescription amphetamine (mostly S ‐amphetamine) and illicit forms of the drug (racemate). In this study, electromembrane extraction with prototype conductive vials was combined with ultra‐high performance supercritical fluid chromatography (UHPSFC‐MS/MS) to quantify R ‐ and S ‐amphetamine in urine. Amphetamine was extracted from 100 μL urine, diluted with 25 μL internal standard solution and 175 μL 130 mM formic acid, across a supported liquid membrane (SLM) consisting of 9 μL of a 1:1(w/w) mixture of 2‐nitrophenyloctyl ether (NPOE) and bis(2‐ethylhexyl)phosphite (DEHPi) into an acceptor phase containing 300 μL 130 mM formic acid. The extraction was facilitated by the application of 30 V for 15 min. Enantiomeric separation was achieved using UHPSFC‐MS/MS with a chiral stationary phase. The calibration range was 50–10,000 ng/mL for each enantiomer. The between‐assay CV was ≤5%, within‐assay CV ≤ 1.5%, and bias within ±2%. Recoveries were 83%–90% (CV ≤ 6%), and internal standard corrected matrix effects were 99–105 (CV ≤ 2%). The matrix effects ranged from 96% to 98% (CV ≤ 8%) when not corrected by the internal standard. The EME method was compared with a chiral routine method that employed liquid–liquid extraction (LLE) for sample preparation. Assay results were in agreement with the routine method, and the mean deviation between methods was 3%, ranging from −21% to 31%. Finally, sample preparation greenness was assessed using the AGREEprep tool, which resulted in a greenness score of 0.54 for conductive vial EME, opposed to 0.47 for semi‐automated 96‐well LLE.
-
Øiestad, Elisabeth Leere; Øiestad, Åse Marit Leere; Middelkoop, Gerrit; Brochmann, Gerd-Wenche; Thaulow, Cecilie Hasselø & Vindenes, Vigdis
(2022).
Comparative Study of Postmortem Concentrations of Benzodiazepines and Z-Hypnotics in Several Different Matrices.
Journal of Analytical Toxicology.
ISSN 0146-4760.
47(3),
p. 287–298.
doi:
10.1093/jat/bkac106.
Full text in Research Archive
Show summary
Abstract Benzodiazepines and z-hypnotics are detected in the majority of fatal overdose cases in Norway, often in combination with other drugs of abuse, and their concentrations in peripheral blood (PB) might be important to elucidate the cause of death. In some forensic autopsies, PB is however not available. The aim of the present study was to compare concentrations of benzodiazepines and z-hypnotics in five alternative matrices to assess whether these concentrations are comparable to concentrations in PB. A total of 109 forensic autopsy cases were included. PB, cardiac blood (CB), pericardial fluid (PF), psoas muscle (PM), lateral vastus muscle (LVM) and vitreous humor (VH) from each case were analyzed using ultra high performance liquid chromatography tandem mass spectrometry. We were able to detect clonazepam, 7-aminoclonazepam, flunitrazepam, 7-aminoflunitrazepam, nitrazepam, 7-aminonitrazepam, diazepam, nordiazepam, oxazepam, alprazolam, midazolam, zopiclone and zolpidem in all the analyzed matrices. Concentrations measured in VH were generally much lower than those of PB for all compounds except zopiclone. 7-Amino metabolite concentrations were high compared to the parent compounds, although less so for the muscle samples. Concentrations of the parent nitrobenzodiazepines in muscles were higher than those in PB, but for the other compounds, concentrations in muscle showed good correspondence with PB. Both CB and PF were viable alternative matrices for PB, although a larger variation and a tendency for higher concentrations in PF were observed. This study shows that CB, PM, LVM and PF can give comparable concentrations to PB for benzodiazepines and z-hypnotics, while VH was less suitable. The concentrations in alternative matrices must, however, be interpreted carefully.
-
Mestad, Ingrid Oksavik; Gjelstad, Astrid; Pedersen-Bjergaard, Stig & Øiestad, Elisabeth Leere
(2021).
Green and sustainable drug analysis – Combining microsampling and microextraction of drugs of abuse.
Sustainable Chemistry and Pharmacy.
24.
doi:
10.1016/j.scp.2021.100517.
Full text in Research Archive
Show summary
A novel method combining microsampling of whole blood containing drugs of abuse with 96-well liquid solution microextraction (Parallel Artificial Liquid Membrane Extraction, PALME) and analysis by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was evaluated. Different donor solutions, supported liquid membranes and acceptor solutions were tested, and the most promising set-up was validated. The method included common classes of drugs of abuse, such as opioids, amphetamines, cocaine, benzodiazepines and z-hypnotics. Extraction recoveries above 70% were found for 13 of the compounds, while the last four compounds had recoveries of 10–58%. THC was not extracted with the current method. A linear calibration model was found for all drugs but morphine. Limits of quantitation were between 1 and 5 ng/mL and inter-day precision and accuracy was within 20% for all compounds except for morphine and zopiclone that had a CV of 25% at LOQ. All matrix effects were within 78–123%. Samples were stable for 14 days except for zopiclone and zolpidem. With low-cost, high sample throughput, semi-automated miniaturized sample preparation in combination with dried blood microsamples, and an Eco-Scale score of 78, the proposed method fulfills green chemistry principles.
-
Skaalvik, Tonje Gottenberg; Øiestad, Elisabeth Leere; Trones, Roger; Pedersen-Bjergaard, Stig & Hegstad, Solfrid
(2021).
Determination of psychoactive drugs in serum using conductive vial electromembrane extraction combined with UHPLC-MS/MS.
Journal of chromatography. B.
ISSN 1570-0232.
1183.
doi:
10.1016/j.jchromb.2021.122926.
Full text in Research Archive
Show summary
Conductive vial electromembrane extraction (EME) with prototype equipment was applied for the first time to extract lipophilic basic drugs from serum. With this equipment, traditional platinum electrodes were replaced with sample and acceptor vials made from a conductive polymer, making the electrodes fully integrated and disposable. EME was combined with UHPLC-MS/MS, and a method to determine selected psychoactive drugs (alimemazine, amitriptyline, atomoxetine, clomipramine, doxepin, duloxetine, fluvoxamine, levomepromazine, nortriptyline and trimipramine) and metabolites (desmethyl clomipramine and desmethyl doxepin) in serum was developed, optimized, and validated. Extractions were carried out with 50 V for 15 min from serum samples (100 µL) diluted 1:3 with formic acid (0.1% v/v), using 2-nitrophenyl octyl ether as the supported liquid membrane (SLM), and formic acid (0.1% v/v, 300 µL) as acceptor phase.
Using conductive vial EME, the extraction of lipophilic drugs reached exhaustive or near-exhaustive conditions, with recoveries in the range 75–117%. The method demonstrated excellent accuracy and precision, with bias within ± 6%, and intra- and inter-day CVs ranging 0.9 – 6% and 2 – 6%, respectively. In addition, acceptor phases were completely free of glycerophosphocholines. EME-UHPLC-MS/MS was successfully applied in determination of psychoactive drugs in 30 patient samples, and the results were in agreement with the current hospital routine method at St. Olav University Hospital (Trondheim, Norway).
Obtaining comparable results to well-established routine methods is highly important for future implementation of EME into routine laboratories. These results thus serve as motivation for further advancing the EME technology. Until now, EME has been carried out with laboratory-build equipment, and the introduction of commercially available standardized equipment is expected to have a positive impact on future research activity.
-
Schüller, Maria; Tran, Kim Tu Thi; Øiestad, Elisabeth Leere & Pedersen-Bjergaard, Stig
(2021).
Membrane-based liquid-phase microextraction of basic pharmaceuticals – A study on the optimal extraction window.
Journal of Chromatography A.
ISSN 0021-9673.
1664(462769).
doi:
10.1016/j.chroma.2021.462769.
Full text in Research Archive
Show summary
The present paper defines the optimal extraction window (OEW) for three-phase membrane-based liquid-phase microextraction (MP-LPME) in terms of analyte polarity (log P), and anchors this to existing theories for equilibrium partitioning and kinetics. Using deep eutectic solvents (DES) as supported liquid membranes (SLM), we investigated how the OEW was affected by ionic-, hydrogen bond and π-π interactions between the SLM and analyte. Eleven basic model analytes in the range -0.4 < log P < 5.0 were extracted by MB-LPME in a 96-well format. Extraction was performed from 250 µL standard solution in 25 mM phosphate buffer (pH 7.0) into 50 µL of 10 mM HCl acceptor solution (pH 2.0) with mixtures of coumarin, camphor, DL-menthol, and thymol, with and without the ionic carrier di(2-ethylhexyl) phosphate (DEHP), as the SLM. The OEW with pure DES was in the range 2 < log P < 5, and low SLM aromaticity was favorable for the extraction of non-polar analytes. Here, extraction recoveries up to 98% were obtained. Upon addition of DEHP to the SLMs, the OEW shifted to the range -0.5 < log P < 2, and a combination of 5% DEHP and moderate aromaticity resulted in extraction recoveries up to 80% for the polar analytes. Extraction with ionic carrier was inefficient for the non-polar analytes, due to excessive trapping in the SLM. The results from our study show that LPME performs optimally in a relatively narrow log P-window of ≈ 2–3 units and that the OEW is primarily affected by ionic carrier and aromaticity.
-
Pettersen, Siren; Øiestad, Åse Marit Leere; Rogde, Sidsel; Brochmann, Gerd-Wenche; Øiestad, Elisabeth Leere & Vindenes, Vigdis
(2021).
Distribution of tetrahydrocannabinol and cannabidiol in several different postmortem matrices.
Forensic Science International.
ISSN 0379-0738.
329:111082,
p. 1–7.
doi:
10.1016/j.forsciint.2021.111082.
Full text in Research Archive
Show summary
Cannabis is the most widely used illicit substance worldwide. A limited number of studies have investigated whether tetrahydrocannabinol (THC) and cannabidiol (CBD) can be detected in other postmortem matrices than blood and urine. The aim of this study was to investigate the distribution of THC and CBD in several different postmortem matrices. Concentrations in peripheral blood were compared to those in cardiac blood, pericardial fluid, psoas muscle, vastus lateralis muscle, and vitreous humor. A total of 39 postmortem forensic autopsy cases were included. THC and CBD were analyzed using gas chromatography-mass spectrometry. We were able to detect both THC and CBD in most of the analyzed matrices. For vitreous humor, however, only approximately 50% of the cases were available for analysis, and only two were found to be positive. Median concentrations in peripheral blood were 0.0040 (0.00042–0.056) mg/L for THC and 0.0013 (0–0.023) mg/L for CBD. The concentration ratios between pericardial fluid and cardiac blood compared to peripheral blood were< 1 for both THC and CBD for the majority of the cases. For THC, a median ratio of 0.60 (0.063–7.2) and 0.65 (0.068–4.8) were found for pericardial fluid and cardiac blood, respectively, compared to peripheral blood, whereas for CBD the corresponding median ratios were 0.40 (0.010–1.9) and 0.80 (0.017–2.4). The THC concentrations in psoas muscle and vastus lateralis muscle were high compared to those in peripheral blood in several cases, and large variations in the muscles to peripheral blood concentration ratios were seen. This was also the case for CBD. Our study shows that THC and CBD can be detected in postmortem matrices other than peripheral blood, and results from other matrices might provide important information in forensic cases where peripheral blood is not available. However, vitreous humor was not suitable for detecting neither THC nor CBD.
-
Hansen, Frederik; Øiestad, Elisabeth Leere & Pedersen-Bjergaard, Stig
(2020).
Bioanalysis of pharmaceuticals using liquid-phase microextraction combined with liquid chromatography–mass spectrometry.
Journal of Pharmaceutical and Biomedical Analysis.
ISSN 0731-7085.
189,
p. 1–12.
doi:
10.1016/j.jpba.2020.113446.
Full text in Research Archive
-
Seljetun, Kristin Opdal; Vindenes, Vigdis; Øiestad, Elisabeth Leere; Brochmann, Gerd-Wenche; Eliassen, Elin & Moe, Lars
(2020).
Determination of anticoagulant rodenticides in faeces of exposed dogs and in a healthy dog population.
Acta Veterinaria Scandinavica (AVS).
ISSN 0044-605X.
62(1),
p. 1–9.
doi:
10.1186/s13028-020-00531-5.
Full text in Research Archive
Show summary
Background Exposure to anticoagulant rodenticides (ARs) in dogs is among the most common causes of poisoning in small animal practice, but information about toxicokinetic of these rodenticides in dogs is lacking. We analysed blood and faeces from five accidentally exposed dogs and 110 healthy dogs by reversed phase ultra-high performance liquid chromatography-tandem mass spectrometry. The aim of the study was to estimate elimination of brodifacoum, bromadiolone and difenacoum after acute exposure, calculate the half-lives of these rodenticides in dogs, estimate faecal elimination in a litter of puppies born, and further to identify the extent of AR exposure in a healthy dog population. Results Three dogs were included after single ingestions of brodifacoum; two dogs ingested bromadiolone and one dog ingested difenacoum. Maximum concentrations in faeces were found after day 2–3 for all ARs. The distribution half-lives were 1–10 days for brodifacoum, 1–2 days for bromadiolone and 10 days for difenacoum. Brodifacoum and difenacoum had estimated terminal half-lives of 200–330 days and 190 days, respectively. In contrast, bromadiolone had an estimated terminal half-life of 30 days. No clinical signs of poisoning or coagulopathy were observed in terminal elimination period. In blood, the terminal half-life of brodifacoum was estimated to 8 days. Faeces from a litter of puppies born from one of the poisoned dogs were examined, and measurable concentrations of brodifacoum were detected in all samples for at least 28 days after parturition. A cross-sectional study of 110 healthy domestic dogs was performed to estimate ARs exposure in a dog population. Difenacoum was detected in faeces of one dog. Blood and faecal samples from the remaining dogs were negative for all ARs. Conclusions Based on the limited pharmacokinetic data from these dogs, our results suggest that ARs have a biphasic elimination in faeces using a two-compartment elimination kinetics model. We have shown that faecal analysis is suitable and reliable for the assessment of ARs exposure in dogs and a tool for estimating the AR half-lives. Half-lives of ARs could be a valuable indicator in the exposed dogs and provides important information for veterinarians monitoring AR exposure and assessment of treatment length in dogs.
-
Hansen, Frederik; Santigosa-Murillo, Elia; Payan, Maria Ramos; Munoz, Maria; Øiestad, Elisabeth Leere & Pedersen-Bjergaard, Stig
(2020).
Electromembrane extraction using deep eutectic solvents as the liquid membrane.
Analytica Chimica Acta.
ISSN 0003-2670.
1143,
p. 109–116.
doi:
10.1016/j.aca.2020.11.044.
Full text in Research Archive
Show summary
In this work, we investigated for the first time hydrophobic deep eutectic solvents (DES) as supported liquid membrane (SLM) for electromembrane extraction (EME). Camphor, coumarin, DL-menthol, and thymol were used as non-ionic DES components. Different DESs compositions were tested, to study systematically the importance of hydrogen bonding and dispersion/aromatic interactions during mass transfer across the SLM. Unexpectedly, mixtures of coumarin and thymol were highly efficient SLMs, and provided exhaustive or near-exhaustive extraction of non-polar bases, non-polar acids, and polar bases. SLMs with such performance for both bases and acids, in a large polarity window, are not found in current literature. The SLMs were highly aromatic, very strong hydrogen bonding donors, and moderately strong hydrogen bonding acceptors. Aromatic (π type) interactions were apparently very important for transfer of bases, while hydrogen bonding were dominant for acids. EME of six polar basic drugs from plasma, with a coumarin and thymol mixture as SLM, and combined with UHPLC-MS/MS analysis, was evaluated to test the potential for analytical applications. Plasma was diluted 1:1 with phosphate buffer pH 2.0. Calibration curves were linear in the therapeutic ranges (0.970 < R2 < 0.999), recoveries ranged between 47 and 93%, and repeatability was within 1.6–10.7% RSD. The clean-up efficiency was excellent and no matrix effects from plasma were seen. Presence of trace levels of coumarin in the acceptor phase was however found to cause some ion enhancement. Based on the current work, we foresee more research on the use of DES in EME.
-
-
Hansen, Frederik; Kuban, Pavel; Øiestad, Elisabeth Leere & Pedersen-Bjergaard, Stig
(2020).
Electromembrane extraction of highly polar bases from biological samples – Deeper insight into bis(2-ethylhexyl) phosphate as ionic carrier.
Analytica Chimica Acta.
ISSN 0003-2670.
1115,
p. 23–32.
doi:
10.1016/j.aca.2020.04.027.
Full text in Research Archive
-
Hansen, Frederik; Jaghl, Mohamad Fadi; Øiestad, Elisabeth Leere; Jensen, Henrik; Pedersen-Bjergaard, Stig & Huang, Chuixiu
(2020).
Impact of ion balance in electromembrane extraction.
Analytica Chimica Acta.
ISSN 0003-2670.
1124,
p. 129–136.
doi:
10.1016/j.aca.2020.05.039.
Full text in Research Archive
-
Seljetun, Kristin Opdal; Sandvik, Morten; Vindenes, Vigdis; Eliassen, Elin; Øiestad, Elisabeth Leere & Madslien, Knut Ivar Engesæter
[Show all 7 contributors for this article]
(2020).
Comparison of anticoagulant rodenticide concentrations in liver and feces from apparently healthy red foxes.
Journal of Veterinary Diagnostic Investigation.
ISSN 1040-6387.
32(4),
p. 560–564.
doi:
10.1177/1040638720927365.
Full text in Research Archive
Show summary
Exposure of wildlife and domestic animals to anticoagulant rodenticides (ARs) is a worldwide concern, but few methods exist to determine residue levels in live animals. Traditional liver detection methods preclude determining exposure in live wildlife. To determine the value of assessing AR exposure by fecal analysis, we compared fecal and liver residues of ARs in the same animals. We collected liver and fecal samples from 40 apparently healthy red foxes (Vulpes vulpes) potentially exposed to ARs, and quantified brodifacoum, bromadiolone, coumatetralyl, difenacoum, difethialone, and flocoumafen residues by liquid chromatography–tandem mass spectrometry. Residues of ARs were detected in 53% of the fecal samples and 83% of the liver samples. We found good concordance between AR residues in feces and liver for coumatetralyl, difenacoum, and difethialone. Bromadiolone occurred in significantly greater frequency in livers compared to feces, but no significant difference in concentration between feces and liver in individual foxes could be detected. Brodifacoum displayed a significant difference in concentration and occurrence of positive samples between liver and feces. Our findings demonstrate that fecal analysis of ARs provides a feasible and valuable non-lethal means of determine AR exposure in live wildlife.
-
Piskackova, Hana Bavlovic; Øiestad, Elisabeth Leere; Vanova, Nela; Lengvarska, Julia; Štěrbová-Kovaříková, Petra & Pedersen-Bjergaard, Stig
(2020).
Electromembrane extraction of anthracyclines from plasma: Comparison with conventional extraction techniques.
Talanta: The International Journal of Pure and Applied Analytical Chemistry.
ISSN 0039-9140.
223.
doi:
10.1016/j.talanta.2020.121748.
Full text in Research Archive
Show summary
Electromembrane extraction (EME) of the polar zwitterionic drugs, anthracyclines (ANT, doxorubicin, daunorubicin and its metabolite daunorubicinol), from rabbit plasma was investigated. The optimized EME was compared to conventional sample pretreatment techniques such as protein precipitation (PP) and liquid-liquid extraction (LLE), mainly in terms of extraction reliability, recovery and matrix effect. In addition, phospholipids profile in the individual extracts was evaluated. The extracted samples were analyzed using UHPLC-MS/MS with electrospray ionization in positive ion mode. The method was validated within the concentration range of 0.25–1000 ng/mL for all tested ANT. Compared with PP and LLE, the EME provided high extraction recovery (more than 80% for all ANT) and excellent sample clean-up (matrix effect were 100 ± 10% with RSD values lower than 4% for all ANT). Furthermore, only negligible amounts of phospholipids were detected in the EME samples. Finally, practical applicability of EME was proved by analysis of plasma samples taken from a pilot in vivo study in rabbits. Consistent results were obtained when using both EME and LLE to extract the plasma prior to the analysis, which further confirmed high reliability of EME. This study clearly showed that EME is a simple, rapid, repeatable technique for extraction of ANT from plasma and it is an up to date alternative to routine conventional extraction techniques.
-
Bretteville-Jensen, Anne Line; Burdzovic, Jasmina; Gjersing, Linn; Øiestad, Elisabeth Leere & Gjerde, Hallvard
(2019).
Identification and Assessment of Drug-User Groups Among Nightlife Attendees: Self-Reports, Breathalyzer-Tests and Oral Fluid Drug Tests.
European Addiction Research.
ISSN 1022-6877.
25(2),
p. 93–102.
doi:
10.1159/000497318.
Full text in Research Archive
Show summary
Background and Objectives: Even though nightlife studies with potentially intoxicated participants provide the much needed information on drug use, they face additional methodological challenges. This study aimed to explore the utility of such studies by (i) classifying nightlife attendees based on their self-reported drug use and by (ii) examining whether these classifications were meaningful when assessed against other sources of data, including oral fluid drug tests. Methods: Self-reported questionnaires, oral fluid samples and blood alcohol concentration readings were collected in a sample of 1,085 nightlife patrons recruited outside 12 popular nightclubs in Oslo, Norway, in 2014. Patrons were classified using multiple approaches, including latent class analysis. Group differences were examined by logistic regression models. Results: Participants were classified into 5 mutually exclusive groups: 2 among current non-users (“Never-users”; “Previous users”), 2 among current users (“Multiple drugs”; “Cannabis mainly”) and one “Incomplete information” group. Meaningful differences across these groups were observed. For instance, positive tests for any illicit drug were more common in “Multiple drugs” group than in “Cannabis mainly” (62.7 vs. 29.1%, adjusted OR [aOR] 3.77 [2.42–5.84]) or “Incomplete information” groups (62.7 vs. 34.4%, aOR 2.46 [1.26–4.79]). Despite their self-declared non-use, illicit substances were detected in oral fluids of “Never-users” (13.1%; 95% CI 9.9–17.2) and “Previous users” (7.9%; 95% CI 5.1–12.1). Conclusions: Despite some discrepancies between self-reports and biological tests, self-reports proved both suitable and useful in identification of substantively different drug-user typologies, potentially informing targeted policy responses. Still, methodological challenges associated with onsite studies of illicit drug use should be further explored.
-
Ask, Kristine Skoglund; Lid, Marthe; Øiestad, Elisabeth Leere; Pedersen-Bjergaard, Stig & Gjelstad, Astrid
(2019).
Liquid-phase microextraction in 96-well plates - calibration and accurate quantification of pharmaceuticals in human plasma samples.
Journal of Chromatography A.
ISSN 0021-9673.
1602,
p. 117–123.
doi:
10.1016/j.chroma.2019.06.013.
Full text in Research Archive
-
Øiestad, Elisabeth Leere; Krabseth, Hege-Merete; Huestis, Marilyn A.; Skulberg, Andreas & Vindenes, Vigdis
(2019).
Interpreting oral fluid drug results in prisoners: monitoring current drug intake and detection times for drugs self-administered prior to detention.
Forensic Toxicology.
ISSN 1860-8965.
37(1),
p. 59–74.
doi:
10.1007/s11419-018-0434-9.
Full text in Research Archive
Show summary
Purpose: Although urine is the most common matrix for prisoner drug testing, oral fluid offers a possible alternative. Identifying new drug intake by a prisoner results in negative sanctions. Detection times in oral fluid after chronic drug intake may be extended. Within the prison, admission population is chronic drug users. Our aim was to investigate detection windows for drugs of abuse in oral fluid from prisoners. Methods: Nineteen frequent drug-abusing prisoners provided oral fluid and urine at admission and each morning thereafter for 9 consecutive days. Results: The most positive findings were for amphetamine/methamphetamine, cannabis and benzodiazepines. Maximum detection times in oral fluid were ≥ 9 days for diazepam, methadone and methamphetamine, with corresponding urinary detection times of ≥ 9, 7 and 6 days, respectively. Maximum oral fluid detection times were 9 days for clonazepam, 8 for oxazepam, 3 for amphetamine and nitrazepam, and 2 for tetrahydrocannabinol, with positive urinary detection times of 8, ≥ 9, 5, 7 and ≥ 9 days, respectively. Cocaine, morphine and 6-acetylmorphine were all positive only 1 day in oral fluid; cocaine and morphine were positive 1 and 2 days, respectively, in urine, while 6-acetylmorphine was not detected in urine. Conclusion: We confirmed oral fluid as a viable matrix for monitoring drugs of abuse in prisoners. Windows of detection for benzodiazepines and amphetamines were up to 1 week, which is an important consideration for evaluating oral fluid drug testing results. Some likely new drug exposures were observed based on urine and oral fluid drug results, but there were few data to guide these interpretations.
-
-
Seljetun, Kristin Opdal; Eliassen, Elin; Madslien, Knut; Viljugrein, Hildegunn; Vindenes, Vigdis & Øiestad, Elisabeth Leere
[Show all 7 contributors for this article]
(2019).
Prevalence of anticoagulant rodenticides in faeces of wild red foxes (Vulpes vulpes) in Norway.
Journal of Wildlife Diseases.
ISSN 0090-3558.
55(4),
p. 834–843.
doi:
10.7589/2019-01-027.
Full text in Research Archive
Show summary
High occurrence of anticoagulant rodenticides (ARs) in wildlife is a rising concern, with
numerous reports of secondary exposure through predation. Because of widespread distribution of the
red fox (Vulpes vulpes), they may act as sentinels for small mammal-hunting predators in rural,
suburban, and urban areas. No AR surveillance in wild mammals with analyses of residues in feces has
been conducted throughout a single country. We collected 163 fecal samples from presumed healthy
red foxes from 18 out of 19 counties in Norway. The foxes were shot during regular hunting between
January and December 2016 and samples collected directly after death. Fecal samples were analyzed
for six ARs: brodifacoum, bromadiolone, coumatetralyl, difenacoum, difethialone, and flocoumafen. We
detected ARs in 54% (75/139) of the animals. Brodifacoum was most frequently detected (46%; 64/139),
followed by coumatetralyl (17%; 23/139), bromadiolone (16%; 22/139), difenacoum (5%; 7/139),
difethialone (1%; 2/139), and flocoumafen (1%; 2/139). More than one substance was detected in 40%
(30/75) of the positive foxes, and 7% (5/75) of these animals were exposed to four different ARs. There
were no statistically significant seasonal, age, or sex differences in foxes after exposure to one AR
compound. We found a significant difference in occurrence of brodifacoum and coumatetralyl in foxes
from different geographical areas. These findings demonstrate fecal analyses as a valuable method of
detecting AR exposure in red foxes. We suggest using direct fecal sampling with analyses as a method to
evaluate the occurrence of ARs in live endangered wildlife in connection with radio tagging or collaring
operations.
-
Vårdal, Linda; Øiestad, Elisabeth Leere; Gjelstad, Astrid; Jensen, Henrik & Pedersen-Bjergaard, Stig
(2019).
Electromembrane extraction with solvent modification of the acceptor solution: improved mass transfer of drugs of abuse from human plasma.
Bioanalysis.
ISSN 1757-6180.
11(8),
p. 755–771.
doi:
10.4155/bio-2018-0308.
Full text in Research Archive
-
Kvello, Anne Marte Sjursen; Andersen, Jannike Mørch; Øiestad, Elisabeth Leere; Steinsland, Synne; Aase, Audun & Mørland, Jørg
[Show all 7 contributors for this article]
(2019).
A monoclonal antibody against 6-acetylmorphine protects female mice offspring from adverse behavioral effects induced by prenatal heroin exposure.
Journal of Pharmacology and Experimental Therapeutics.
ISSN 0022-3565.
368(1),
p. 106–115.
doi:
10.1124/jpet.118.251504.
Full text in Research Archive
-
-
-
Ask, Kristine Skoglund; Øiestad, Elisabeth Leere; Pedersen-Bjergaard, Stig & Gjelstad, Astrid
(2018).
Dried blood spots and parallel artificial liquid membrane extraction – A simple combination of microsampling and microextraction.
Analytica Chimica Acta.
ISSN 0003-2670.
1009,
p. 56–64.
doi:
10.1016/j.aca.2018.01.024.
Full text in Research Archive
-
Øiestad, Åse Marit Leere; Berg, Thomas; Eliassen, Elin; Wiklund, Tony; Sand, Ketil & Øiestad, Elisabeth Leere
(2018).
Separation of isomers of new psychoactive substances and isotope-labeled amphetamines using UHPSFC-MS/MS and UHPLC-MS/MS.
Journal of Liquid Chromatography & Related Technologies.
ISSN 1082-6076.
41(7),
p. 391–400.
doi:
10.1080/10826076.2017.1388818.
Full text in Research Archive
-
Vårdal, Linda; Wong, Gladys; Øiestad, Åse Marit Leere; Pedersen-Bjergaard, Stig; Gjelstad, Astrid & Øiestad, Elisabeth Leere
(2018).
Rapid determination of designer benzodiazepines, benzodiazepines, and Z-hypnotics in whole blood using parallel artificial liquid membrane extraction and UHPLC-MS/MS.
Analytical and Bioanalytical Chemistry.
ISSN 1618-2642.
410(20),
p. 4967–4978.
doi:
10.1007/s00216-018-1147-y.
Full text in Research Archive
-
Øiestad, Åse Marit Leere; Karinen, Ritva Anneli; Rogde, Sidsel; Nilsen, Stian; Eldor, Kari Beate Boye & Brochmann, Gerd-Wenche
[Show all 11 contributors for this article]
(2018).
Comparative study of postmortem concentrations of antidepressants in several different matrices.
Journal of Analytical Toxicology.
ISSN 0146-4760.
42(7),
p. 446–458.
doi:
10.1093/jat/bky030.
Full text in Research Archive
Show summary
Peripheral blood (PB) is considered to be the golden standard for measuring postmortem drug concentrations. In several cases, PB is however not available, but information regarding drug findings might still be crucial in order to determine the cause of death. Antidepressants are frequently detected in postmortem samples from forensic toxicology cases, but the literature investigating concentrations in other matrices than peripheral and heart blood is limited. We here describe a study for comparison of concentrations for a large number of different drugs in six different matrices. A total of 173 postmortem cases were included in the study material. The results from 44 cases with findings of antidepressants (amitriptyline/nortriptyline, citalopram, mianserin, mirtazapine, paroxetine, sertraline, trimipramine and venlafaxine) are presented in this article. Concentrations in peripheral and cardiac blood (CB), pericardial fluid (PF), two muscle samples and vitreous humour (VH) are compared. Ratios between concentrations in different matrices have also been compiled from available literature. All the investigated antidepressants were detected in all different matrices, and comparable concentration levels were found in the different matrices with a few exceptions. Concentrations in VH were generally lower than in the other matrices, and in a few cases with low concentrations in blood the antidepressants were not detected in VH. For most of the cases, ratios of 0.5–2 were found between concentration in PB and that in the other matrices. Some deviant concentrations where however found. This study shows that CB, PF, muscle and VH can provide important indications of the corresponding concentrations in PB when PB is not available.
-
Vårdal, Linda; Øiestad, Elisabeth Leere; Gjelstad, Astrid & Pedersen-Bjergaard, Stig
(2018).
Electromembrane extraction of substances with weakly basic properties: A fundamental study with benzodiazepines.
Bioanalysis.
ISSN 1757-6180.
10(10),
p. 769–781.
doi:
10.4155/bio-2018-0030.
Full text in Research Archive
-
Vevelstad, Merete; Øiestad, Elisabeth Leere; Nerem, Elisabeth; Arnestad, Marianne & Bogen, Inger Lise
(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 Metabolism And Disposition.
ISSN 0090-9556.
45(12),
p. 1326–1335.
doi:
10.1124/dmd.117.077263.
Full text in Research Archive
-
Valen, Anja; Øiestad, Elisabeth Leere; Strand, Dag Helge; Skari, Ragnhild Margrete & Berg, Thomas
(2017).
Determination of 21 drugs in oral fluid using fully automated supported liquid extraction and UHPLC-MS/MS.
Drug Testing and Analysis.
ISSN 1942-7603.
9(5),
p. 808–823.
doi:
10.1002/dta.2045.
Full text in Research Archive
-
Vallersnes, Odd Martin; Persett, Per Sverre; Øiestad, Elisabeth Leere; Karinen, Ritva Anneli; Heyerdahl, Fridtjof & Hovda, Knut Erik
(2017).
Underestimated impact of novel psychoactive substances: laboratory confirmation of recreational drug toxicity in Oslo, Norway.
Clinical Toxicology.
ISSN 1556-3650.
55(7),
p. 636–644.
doi:
10.1080/15563650.2017.1312002.
Full text in Research Archive
Show summary
Context: Recreational drug toxicity is frequent. Availability of new psychoactive substances is steadily increasing. However, data with verified analyses from clinical settings are limited. To evaluate the impact of novel psychoactive substances (NPS) on recreational drug toxicity in Oslo, Norway, we analysed samples from a selection of patients. Methods: All the patients presenting with recreational drug toxicity at the Oslo Accident and Emergency Outpatient Clinic (OAEOC) and at the Oslo University Hospital (OUH) were registered from April through September 2014. Oral fluid samples were collected at the OAEOC. Blood samples were collected at the OUH. The samples were screened using ultra-high performance liquid chromatography – tandem mass spectrometry (UHPLC-MS/MS). Results: Nine hundred and sixty-four cases were included, 841 (87.2%) at the OAEOC and 123 (12.8%) at the OUH. A total of 55 oral fluid samples (OAEOC) and 103 blood samples (OUH) could be analysed. NPS were not clinically suspected in any of the screened cases. At the outpatient clinic, the most commonly found substances were clonazepam in 42/55 (76.4%) cases, amfetamines in 40/55 (72.7%) and heroin in 39/55 (70.9%). In seven (12.7%) cases NPS were detected: 4-methylamfetamine in three cases, dimethyltryptamine in two, methylone in one, and N,N-dimethyl-3,4-methylenedioxyamfetamine in one. Among the hospital patients, the most commonly found substances were clonazepam in 51/103 (49.5%) cases, amfetamines in 48/103 (46.6%), heroin in 31/103 (30.1%), and diazepam in 30/103 (29.1%). In five (4.9%) cases NPS were detected: JWH-210 in two cases, AM-2201 in two, and 5-EAPB in one. Conclusion: NPS were clinically not suspected, though found in eight percent of cases. Still, the vast majority of patients treated for recreational drug toxicity in Oslo have taken classical drugs. Management of these patients should be based on their clinical condition. However, it is highly important to be alert to atypical presentations possibly resulting from unsuspected drugs. This is an Accepted Manuscript of an article published by Taylor & Francis Group in Clinical Toxicology on 13/04/2017, available online: http://www.tandfonline.com/10.1080/15563650.2017.1312002
-
Vårdal, Linda; Gjelstad, Astrid; Huang, Chuixiu; Øiestad, Elisabeth Leere & Pedersen-Bjergaard, Stig
(2017).
Efficient discrimination and removal of phospholipids during electromembrane extraction from human plasma samples.
Bioanalysis.
ISSN 1757-6180.
9(8),
p. 631–641.
doi:
10.4155/bio-2017-0027.
Full text in Research Archive
-
Hjelmeland, Knut Johan; Gustavsen, Ingebjørg G.; Øiestad, Elisabeth Leere; Øiestad, Åse Marit Leere; Høiseth, Gudrun & Mørland, Jørg
(2017).
Zopiclone concentrations in oral fluid and blood after, administration of therapeutic doses of zopiclone.
Forensic Science International.
ISSN 0379-0738.
278,
p. 177–183.
doi:
10.1016/j.forsciint.2017.07.004.
Full text in Research Archive
-
Vårdal, Linda; Askildsen, Hilde- Merete; Gjelstad, Astrid; Øiestad, Elisabeth Leere; Edvardsen, Hilde Marie Erøy & Pedersen-Bjergaard, Stig
(2017).
Parallel artificial liquid membrane extraction of new psychoactive substances in plasma and whole blood.
Journal of chromatography. B.
ISSN 1570-0232.
1048,
p. 77–84.
doi:
10.1016/j.jchromb.2017.02.010.
Full text in Research Archive
-
-
Kvello, Anne Marte Sjursen; Andersen, Jannike Mørch; Øiestad, Elisabeth Leere; Mørland, Jørg & Bogen, Inger Lise
(2016).
Pharmacological Effects of a Monoclonal Antibody against
6-Monoacetylmorphine upon Heroin-Induced Locomotor Activity
and Pharmacokinetics in Mice.
Journal of Pharmacology and Experimental Therapeutics.
ISSN 0022-3565.
358(2),
p. 181–189.
doi:
10.1124/jpet.116.233510.
Full text in Research Archive
-
-
Øiestad, Elisabeth Leere; Øiestad, Åse Marit Leere; Gjelstad, Astrid & Karinen, Ritva Anneli
(2016).
Oral fluid drug analysis in the age of new psychoactive substances.
Bioanalysis.
ISSN 1757-6180.
8(7),
p. 691–710.
doi:
10.4155/bio-2015-0027.
Full text in Research Archive
Show summary
Oral fluid has become an important matrix for drugs of abuse analysis. These days the applicability is challenged by the fact that an increasing number of new psychoactive drugs are coming on the market. Synthetic cannabinoids and synthetic cathinones have been the main drug classes, but the diversity is increasing and other drugs like piperazines, phenethylamines, tryptamines, designer opioids and designer benzodiazepines are becoming more prevalent. Many of the substances are very potent, and low doses ingested will lead to low concentrations in biological media, including oral fluid. This review will highlight the phenomenon of new psychoactive substances and review methods for oral fluid drug testing analysis using on-site tests, immunoassays and chromatographic methods.
-
Vevelstad, Merete; Øiestad, Elisabeth Leere; Bremer, Sara; Bogen, Inger Lise; Zackrisson, Anna-Lena & Arnestad, Marianne
(2016).
Is toxicity of PMMA (paramethoxymethamphetamine) associated with cytochrome P450 pharmacogenetics?
Forensic Science International.
ISSN 0379-0738.
261,
p. 137–147.
doi:
10.1016/j.forsciint.2016.02.027.
Full text in Research Archive
-
Gjerde, Hallvard; Nordfjærn, Trond; Bretteville-Jensen, Anne Line; Edland-Gryt, Marit; Furuhaugen, Håvard & Karinen, Ritva Anneli
[Show all 7 contributors for this article]
(2016).
Comparison of drugs used by nightclub patrons and criminal offenders in Oslo, Norway.
Forensic Science International.
ISSN 0379-0738.
265,
p. 1–5.
doi:
10.1016/j.forsciint.2015.12.029.
Full text in Research Archive
Show summary
The aim of this study was to investigate psychoactive drug use among nightclub patrons by analysing samples of oral fluid and compare with findings in blood samples from criminal suspects. We hypothesized that the profile of illicit drug use among nightclub patrons is different from what we observe in those forensic cases. Research stations were established outside nine popular nightclubs with different profiles and patron-characteristics in downtown Oslo. Data and sample collection was conducted on Fridays and Saturdays in March and May 2014. Individuals and groups who entered defined recruitment zones from 23:00 to 03:30 were invited to participate in this voluntary and anonymous study. Oral fluid was collected using the Intercept Oral Fluid Sampling Device. Methanol was added to increase the recovery of cannabinoids from the device. Sample preparation was performed using liquid–liquid extraction with ethyl acetate/heptane (4:1) after adding internal standards, ammonium carbonate buffer pH 9.3 and Triton X100. The first 80 samples were analysed for 122 substances, which included psychoactive medicinal drugs, classical illicit drugs and new psychoactive substances (NPS). Based on the findings and discussions with police and customs authorities, the remaining oral fluid samples were analysed for 46 substances. Among the 500 samples collected during the study period, we found illicit drugs in 25.4% and medicinal drugs in 4.2% of the samples. The most prevalent substances were: cocaine 14.6%, THC 12.4%, amphetamine/methamphetamine 2.8%, diazepam 1.2% and clonazepam 1.0%. Various NPS were found in 1.4% of the samples. The prevalence of drugs in blood samples from criminal suspects were for cocaine 3.4%, THC 34.7%, amphetamine/methamphetamine 37.0%, diazepam 12.0%, and clonazepam 29.3%. Multi-drug use was more common among criminal suspects (41.3%) than among club patrons (6.8%). The results showed that the drug use pattern among nightclub patrons was substantially different from the drug use pattern manifested by individuals apprehended by the police suspected for criminal conduct.
-
-
-
Nordal, Kristin; Øiestad, Elisabeth Leere; Enger, Asle; Christophersen, Asbjørg S. & Vindenes, Vigdis
(2015).
Detection Times of Diazepam, Clonazepam, and Alprazolam in Oral Fluid Collected From Patients Admitted to Detoxification, After High and Repeated Drug Intake.
Therapeutic Drug Monitoring.
ISSN 0163-4356.
37(4),
p. 451–460.
doi:
10.1097/FTD.0000000000000174.
Full text in Research Archive
-
Karinen, Ritva Anneli; Tuv, Silja Skogstad; Øiestad, Elisabeth Leere & Vindenes, Vigdis
(2015).
Concentrations of APINACA, 5F-APINACA, UR-144 and its degradant product in blood samples from six impaired drivers compared to previous reported concentrations of other synthetic cannabinoids.
Forensic Science International.
ISSN 0379-0738.
246,
p. 98–103.
doi:
10.1016/j.forsciint.2014.11.012.
Full text in Research Archive
-
Gottås, André; Ripel, Åse; Boix, Fernando; Vindenes, Vigdis; Mørland, Jørg & Øiestad, Elisabeth Leere
(2015).
Determination of dopamine concentrations in brain extracellular fluid using microdialysis with short sampling intervals, analyzed by ultra high performance liquid chromatography tandem mass spectrometry.
Journal of pharmacological and toxicological methods.
ISSN 1056-8719.
74,
p. 75–79.
doi:
10.1016/j.vascn.2015.06.002.
Full text in Research Archive
-
Karinen, Ritva Anneli; Vindenes, Vigdis; Hasvold, Inger; Olsen, Kirsten Midtbøen; Christophersen, Asbjørg S. & Øiestad, Elisabeth Leere
(2015).
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 Testing and Analysis.
ISSN 1942-7603.
7(7),
p. 634–644.
doi:
10.1002/dta.1733.
Full text in Research Archive
Show summary
Quantitative determination of anti-epileptic drug concentrations is of great importance in forensic toxicology cases. Although the drugs are not usually abused, they are important post-mortemcaseswhere the question of both lack of compliance and accidental
or deliberate poisoningmight be raised. In addition these drugs can be relevant for driving under the influence cases. A reversed phase ultra-performance liquid chromatography-tandem mass spectrometry method has been developed for the quantitative analysis of the anti-epileptic compounds carbamazepine, carbamazepine-10,11-epoxide, gabapentin, lamotrigine, levetiracetam,
oxcarbazepine, 10-OH-carbazepine, phenobarbital, phenytoin, pregabalin, and topiramate in whole blood, using 0.1mL sample volume with methaqualone as internal standard. Sample preparation was a simple protein precipitation with acetonitrile and methanol. The diluted supernatant was directly injected into the chromatographic system. Separation was performed on an Acquity UPLC® BEH Phenyl column with gradient elution and a mildly alkaline mobile phase. The mass spectrometric detection wasperformed inpositive ionmode, except for phenobarbital, andmultiple reactionmonitoringwas used for drugquantification.
The limits of quantification for the different anti-epileptic drugs varied from0.064 to 1.26mg/L in blood, within-day and day-to-day relative standard deviations from2.2 to 14.7%except for phenobarbital. Between-day variation for phenobarbitalwas 20.4% at the concentration level of 3.5mg/L. The biases for all compounds were within ±17.5%. The recoveries ranged between 85 and 120%. The correctedmatrix effectswere 88–106% and 84–110%in ante-mortemand post-mortemwhole blood samples, respectively.
-
-
Vindenes, Vigdis; Enger, Arve; Nordal, Kristin; Johansen, Unni; Christophersen, Asbjørg S. & Øiestad, Elisabeth Leere
(2014).
Very long detection times after high and repeated intake of heroin and methadone, measured in oral fluid :.
Scandinavian Journal of Forensic Science.
ISSN 1503-9552.
20(2),
p. 34–41.
doi:
10.2478/sjfs-2014-0004.
Full text in Research Archive
-
Lund, Hilde Marie Erøy; Karinen, Ritva Anneli; Moan, Inger Synnøve; Øiestad, Elisabeth Leere; Christophersen, Asbjørg S & Gjerde, Hallvard
(2014).
Use of alcohol and drugs among health professionals in Norway: a study using data from questionnaires and samples of oral fluid.
Journal of Occupational Medicine and Toxicology.
9.
doi:
10.1186/1745-6673-9-8.
Full text in Research Archive
-
Øiestad, Elisabeth Leere; Karinen, Ritva Anneli; Christophersen, Asbjørg S.; Vindenes, Vigdis & Bachs, Liliana Casulleras
(2014).
Analyses of Beverage Remains in Drug Rape Cases Revealing Drug Residues - The Possibility of Contamination from Drug Concentrated Oral Fluid or Oral Cavity Contained Tablets.
Journal of Forensic Sciences.
ISSN 0022-1198.
59(1),
p. 208–210.
doi:
10.1111/1556-4029.12270.
Full text in Research Archive
-
Gottås, André; Boix, Fernando; Øiestad, Elisabeth Leere; Vindenes, Vigdis & Mørland, Jørg
(2014).
Role of 6-monoacetylmorphine in the acute release of striatal dopamine induced by intravenous heroin.
International Journal of Neuropsychopharmacology.
ISSN 1461-1457.
17(9),
p. 1357–1365.
doi:
10.1017/S1461145714000169.
Full text in Research Archive
-
Tuv, Silja Skogstad; Krabseth, Hege-Merete; Karinen, Ritva Anneli; Olsen, Kirsten Midtbøen; Øiestad, Elisabeth Leere & Vindenes, Vigdis
(2014).
Prevalence of synthetic cannabinoids in blood samples from Norwegian drivers suspected of impaired driving during a seven weeks period.
Accident Analysis and Prevention.
ISSN 0001-4575.
62,
p. 26–31.
doi:
10.1016/j.aap.2013.09.009.
Full text in Research Archive
-
-
-
Eibak, Lars Erik; Rasmussen, Knut Einar; Øiestad, Elisabeth Leere; Pedersen-Bjergaard, Stig & Gjelstad, Astrid
(2014).
Parallel electromembrane extraction in the 96-well format.
Analytica Chimica Acta.
ISSN 0003-2670.
828,
p. 46–52.
doi:
10.1016/j.aca.2014.04.038.
Full text in Research Archive
-
Lund, Hilde Marie Erøy; Gjerde, Hallvard; Courtade, Sandra Monica Bach de; Øiestad, Elisabeth Leere & Christophersen, Asbjørg S
(2013).
A Norwegian Study of the Suitability of Hair Samples in Epidemiological Research of Alcohol, Nicotine and Drug Use.
Journal of Analytical Toxicology.
ISSN 0146-4760.
37(6),
p. 362–368.
doi:
10.1093/jat/bkt038.
Full text in Research Archive
-
Øiestad, Elisabeth Leere; Johansen, Unni; Christophersen, Asbjørg S & Karinen, Ritva Anneli
(2013).
Screening of synthetic cannabinoids in preserved oral fluid by UPLC-MS/MS.
Bioanalysis.
ISSN 1757-6180.
5(18),
p. 2257–2268.
doi:
10.4155/bio.13.182.
Full text in Research Archive
-
-
Gjerde, Hallvard; Christophersen, Asbjørg S; Normann, Per Trygve; Assum, Terje; Øiestad, Elisabeth Leere & Mørland, Jørg
(2013).
Norwegian roadside survey of alcohol and drug use by drivers (2008-2009).
Traffic Injury Prevention.
ISSN 1538-9588.
14(5),
p. 443–452.
doi:
10.1080/15389588.2012.728016.
Full text in Research Archive
Show summary
Objective: To examine alcohol and drug use among random drivers in different regions of Norway by analyzing oral fluid, compare drivers in urban and rural areas, compare with results from the roadside survey in southeastern Norway in 2005–2006, and roughly estimate the prevalence of driving with blood drug concentrations above the new Norwegian legislative limits among random drivers. This roadside survey was part of the European DRUID (Driving Under the Influence of Drugs, Alcohol and Medicines) Project.
Methods: Drivers were selected for a voluntary and anonymous study using a stratified multistage cluster sampling procedure in collaboration with the Mobile Police Service. Samples of oral fluid were taken using the Statsure Saliva Sample (Statsure Diagnostic Systems, Framingham, MA), and the drivers’ gender, age, and nationality were recorded. Samples of oral fluid were analyzed for alcohol or drugs, for a total 28 psychoactive substances.
Results: One hundred eighty-four roadside survey sessions were conducted and 10,004 drivers were asked to participate. The refusal rate was 5.8 percent. Psychoactive substances were found in 4.8 percent of the 9410 oral fluid samples analyzed. Alcohol was detected in 0.3 percent, medicinal drugs in 3.2 percent, and illegal drugs in 1.5 percent of the samples. Illegal drugs were significantly more frequently detected in samples from southeastern Norway including the capital Oslo, whereas medicinal drugs were more frequently detected in samples from southeastern Norway excluding Oslo. Illegal drugs were significantly more frequently detected in samples from drivers in urban areas than in rural areas, though there were no significant differences for alcohol and medicinal drugs. Medicinal drugs were most commonly found in samples collected during the daytime on weekdays (3.8%), and illegal drugs were most commonly found in samples collected during late night on weekdays or weekends (2.8%–3.2%). The most commonly found substances were the sleeping agent zopiclone (1.4%), the main active substance in cannabis tetrahydrocannabinol (1.1%), and the sedative drug diazepam (0.7%). The prevalence of driving with drug concentrations above the Norwegian legislative limits for blood was estimated to be about 0.2 percent for alcohol, 0.6 percent for illegal drugs, and about 1.3 percent for medicinal drugs.
Conclusions: The incidence of drink driving was very low, though driving after using psychoactive illegal or medicinal drugs was more frequent.
Supplemental materials are available for this article. Go to the publisher's online edition of Traffic Injury Prevention to view the supplemental file.
-
Karinen, Ritva Anneli; Johnsen, Lene; Andresen, Wenche; Christophersen, Asbjørg S.; Vindenes, Vigdis & Øiestad, Elisabeth Leere
(2013).
Stability Study of Sixteen Synthetic Cannabinoids of Aminoalkylindole Type in Whole Blood, Stored in Venoject® Evacuated Glass Tubes.
Journal of Forensic Toxicology & Pharmacology.
ISSN 2325-9841.
2(1).
doi:
10.4172/2325-9841.1000106.
Full text in Research Archive
-
Wangberg, Lise Storhaug; Enger, Arve; Hjelmeland, Knut Johan; Øiestad, Elisabeth Leere & Vindenes, Vigdis
(2012).
Prolonged excretion of 7-aminoclonazepam in urine after repeated ingestion of clonazepam: A case report.
Forensic Science International.
ISSN 0379-0738.
222(1-3),
p. e33–e35.
doi:
10.1016/j.forsciint.2012.06.018.
Full text in Research Archive
-
-
View all works in NVA
-
-
-
-
-
Seljetun, Kristin Opdal; Vindenes, Vigdis; Brochmann, Gerd-Wenche; Eliassen, Elin; Øiestad, Elisabeth Leere & Moe, Lars
(2020).
Perinatal transmission of an anticoagulant rodenticide in a dog.
Clinical Toxicology.
ISSN 1556-3650.
58,
p. 535–536.
Full text in Research Archive
-
-
-
-
Ask, Kristine Skoglund; Øiestad, Elisabeth Leere; Pedersen-Bjergaard, Stig & Gjelstad, Astrid
(2016).
Parallel Artificial Liquid Membrane Extraction - En ny metode for fjerning av fosfolipider.
Full text in Research Archive
-
Hjelmeland, Knut Johan; Gustavsen, Ingebjørg G.; Øiestad, Elisabeth Leere; Øiestad, Åse Marit Leere & Mørland, Jørg
(2016).
COMPARISION OF ZOPICLONE CONCENTRATIONS IN
BLOOD AND ORAL FLUID.
Full text in Research Archive
-
-
-
-
Vårdal, Linda; Øiestad, Elisabeth Leere; Seip, Knut Fredrik; Gjelstad, Astrid & Pedersen-Bjergaard, Stig
(2015).
Development of Stable, Selective, and
Efficient Artificial Liquid Membranes for Electromembrane Extraction (EME).
Full text in Research Archive
-
Gjerde, Hallvard; Christophersen, Asbjørg S.; Øiestad, Elisabeth Leere & Vindenes, Vigdis
(2014).
Bruk av biologiske prøver til kartlegging av rusmiddelbruk.
Full text in Research Archive
-
Øiestad, Elisabeth Leere; Krabseth, Hege-Merete; Skulberg, Andreas & Vindenes, Vigdis
(2013).
Elimination of drugs of abuse in oral fluid from prison inmates compared to urine samples.
Full text in Research Archive
-
-
Øiestad, Elisabeth Leere; Karinen, Ritva Anneli; Tuv, Silja Skogstad; Bachs, Liliana & Vindenes, Vigdis
(2013).
Syntetiske cannabinoider - påvisning i blod og spytt.
Full text in Research Archive
-
Edvardsen, Hilde Marie Erøy; Gjerde, Hallvard; Moan, Inger Synnøve; Øiestad, Elisabeth Leere & Christophersen, Asbjørg S
(2013).
Er helsepersonell i Norge på jobb i rus eller bakrus?
Full text in Research Archive
-
Lund, Hilde Marie Erøy; Gjerde, Hallvard; Øiestad, Elisabeth Leere & Christophersen, Asbjørg S.
(2013).
Rusmiddelbruk blant helsepersonell på jobb i Norge.
Full text in Research Archive
-
Vevelstad, Merete; Vege, Åshild; Arnestad, Marianne; Bogen, Inger Lise & Øiestad, Elisabeth Leere
(2018).
Para-methoxymethamphetamine (PMMA): A study of risk factors for fatal intoxication with emphasis on metabolite pattern and CYP genetics.
Universitetet i Oslo.
Full text in Research Archive
Show summary
PMMA (para-methoxymethamphetamine) is, for unknown reasons, more toxic than MDMA (ecstasy). This thesis assessed risk factors for a fatal PMMA intoxication, with emphasis on CYP enzyme genetics, PMMA metabolite pattern, and active metabolites. This was accomplished by analyzing blood samples from fatal PMMA intoxications and non-fatal PMMA abuse cases for CYP genotypes, PMMA, and relevant metabolites, and by studies using human liver microsomes (HLM). During 2010-2012, 27 fatal PMMA intoxications were registered in Norway. The CYP2D6 enzyme was vital for the formation of most metabolites. We found no association between CYP2D6, 2C9, 2C19, or 3A5 enzyme genotypes and fatal outcome. PMMA was partly metabolized to the reactive catechol dihydroxymethamphetamine in HLM, but in lower amounts than formed from MDMA. The main risk factors were high/repeated doses of PMMA, concomitant use of (meth)amphetamine or heroin, unattended sleep, and unwitting intake of PMMA. Witnessed signs of poisoning were severe hyperthermia, convulsions, respiratory failure, unconsciousness, and cardiac arrest, attributable to a pronounced increase in serotonin and noradrenalin neurotransmission.
-
Lund, Hilde Marie Erøy; Øiestad, Elisabeth Leere; Christophersen, Asbjørg S.; Gjerde, Hallvard & Pedersen-Bjergaard, Stig
(2015).
Using biological samples to study the use of alcohol and drugs in cohorts.
Universitetet i Oslo.
Full text in Research Archive
-
Gottås, Andre; Mørland, Jørg; Boix, Fernando; Øiestad, Elisabeth Leere & Vindenes, Vigdis
(2014).
Pharmacokinetics of heroin and heroin metabolites and its relation to the striatal dopaminergic response in a rat model.
Universitetet i Oslo.
ISSN 9788282647984.
Full text in Research Archive
-
View all works in NVA
Published
Mar. 28, 2014 12:48 PM
- Last modified
Jan. 22, 2021 8:54 AM