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  • 1.
    Bendtsen, Preben
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, Division of Preventive and Social Medicine and Public Health Science. Östergötlands Läns Landsting, Centre for Public Health Sciences, Centre for Public Health Sciences.
    Jones, AW
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Forensic Medicine.
    Impact of water-induced diuresis on excretion profiles of ethanol, urin-creatinine, and urine-osmolality. 1999In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 23, p. 565-569Article in journal (Refereed)
  • 2.
    Forsman, M.
    et al.
    National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Artillerigatan 12, SE 587 58, Linköping, Sweden.
    Nystrom, I.
    National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Artillerigatan 12, SE 587 58, Linköping, Sweden.
    Roman, M.
    National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Artillerigatan 12, SE 587 58, Linköping, Sweden.
    Berglund, L.
    National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Artillerigatan 12, SE 587 58, Linköping, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Kronstrand, Robert
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Urinary detection times and excretion patterns of flunitrazepam and its metabolites after a single oral dose2009In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 33, no 8, p. 491-501Article in journal (Refereed)
    Abstract [en]

    We investigated the excretion profiles of flunitrazepam metabolites in urine after a single dose. Sixteen volunteers received either 0.5 or 2.0 mg flunitrazepam. Urine samples were collected after 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 240, and 336 h. Samples were screened using CEDIA (300 µg/L cutoff) and quantitated using liquid chromatography-tandem mass spectrometry. The cutoff was 0.5 µg/L for flunitrazepam, N-desmethylflunitrazepam, 7-aminoflunitrazepam, 7-aminodesmethylflunitrazepam, 7-acetamidoflunitrazepam, and 7-acetamidodesmethylflunitrazepam. None of the subjects receiving 0.5 mg were screened positive, and only 23 of 102 samples from the subjects given 2.0 mg were positive with CEDIA. The predominant metabolites were 7-aminoflunitrazepam and 7-aminodesmethylflunitrazepam. For all subjects given the low dose, 7-aminoflunitrazepam was detected up to 120 h, and for two subjects for more than 240 h. Seven subjects given the high dose were positive up to 240 h for 7-aminoflunitrazepam. We conclude that the ratio 7-aminodesmethylflunitrazepam to 7-aminoflunitrazepam increased with time, independent of dose, and may be used to estimate the time of intake. For some low-dose subjects, the metabolite concentrations in the early samples were low and a chromatographic method may fail to detect the intake. We think laboratories should consider this when advising police and hospitals about sampling as well as when they set up strategies for analysis.

  • 3.
    Guerrieri, Davide
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Kjellqvist, Fanny
    Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Artillerigatan 12, SE-58758 Linkoping, Sweden.
    Kronstrand, Robert
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Artillerigatan 12, SE-58758 Linkoping, Sweden.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Artillerigatan 12, SE-58758 Linkoping, Sweden.
    Validation and Cross-Reactivity Data for Fentanyl Analogs With the Immunalysis Fentanyl ELISA2019In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 43, no 1, p. 18-24Article in journal (Refereed)
    Abstract [en]

    Every year new fentanyl analog compounds, or fentanyls, appear on the drug scene. Development of immunoassays dedicated for screening individual molecules is challenging due to the short-lived presence of these compounds on the recreational drug market. Therefore, we investigated the detecting capabilities of the immunalysis fentanyl direct enzyme-linked immunosorbent assay (ELISA) kit against fentanyl in whole blood, and determined the cross-reactivity of nine fentanyl analogs (2-fluorofentanyl, acetylfentanyl, acrylfentanyl, carfentanil, cyclopropylfentanyl, tetrahydrofuranylfentanyl, furanylfentanyl, ocfentanil, valerylfentanyl) to confirm its validity for the general screening of fentanyls. Immunalysis ELISA assay was used to test whole blood samples fortified with fentanyl on a TECAN Freedom EVOlyzer platform, according to manufacturer specifications. The kit successfully was validated for fentanyl screening with a cutoff set at 0.5 ng/mL, and all tested analogs, with the exclusion of carfentanil, were detected. The lowest cross-reactivity with the kit was obtained with furanylfentanyl (20% +/- 1, 95% confidence intervals (CI)) and 4-fluoroisobutyrfentanyl (25% +/- 1, 95% CI), while the highest was recorded using acetylfentanyl (99% +/- 11, 95% CI) and acrylfentanyl (94% +/- 10, 95% CI). Post-mortem samples containing fentanyl, acrylfentanyl, cyclopropylfentanyl, THF-fentanyl and 4-fluoroisobutyrfentanyl were screened, and sensitivity and specificity of each analog were calculated. Positive screening results were generated by all post-mortem cases containing fentanyl (n = 14), acrylfentanyl (n = 11), cyclopropylfentanyl (n = 14), tetrahydrofuranylfentanyl (n = 13) and 4-fluoroisobutyrfentanyl (n = 10). Concentration of post-mortem fentanyl samples ranged from 0.5 ng/mL (cutoff) to 230 ng/mL, while the range for analogs was 3.4-36 ng/mL (cyclopentylfentanyl), 0.76-370 ng/mL (4-fluoroisobutyrfentanyl), 0.02-12 ng/mL (acrylfentanyl) and 2-26 ng/mL (tetrahydrofuranylfentanyl). The immunalysis fentanyl direct ELISA kit was successfully validated and showed significant cross-reactivity for all tested fentanyls, except carfentanil, making it a suitable technique for fentanyl and fentanyl analogs screening.

  • 4.
    Guerrieri, Davide
    et al.
    National Board Forens Med, Department Forens Genet and Forens Toxicol, S-58758 Linkoping, Sweden.
    Rapp, Emma
    National Board Forens Med, Department Forens Genet and Forens Toxicol, S-58758 Linkoping, Sweden.
    Roman, Markus
    National Board Forens Med, Department Forens Genet and Forens Toxicol, S-58758 Linkoping, Sweden.
    Druid, Henrik
    Karolinska Institute, Sweden.
    Kronstrand, Robert
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. National Board Forens Med, Department Forens Genet and Forens Toxicol, S-58758 Linkoping, Sweden.
    Postmortem and Toxicological Findings in a Series of Furanylfentanyl-Related Deaths2017In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 41, no 3, p. 242-249Article in journal (Refereed)
    Abstract [en]

    Over the course of 4 months in 2015 and 2016, a cluster of seven fatal intoxications involving the opioid-analogue furanylfentanyl occurred in Sweden; toxicological analysis showed presence of furanylfentanyl either as the only drug or in combination with other illicit substances. Previous publications have only reported non-lethal furanylfentanyl intoxications. In the cases presented here, furanylfentanyl intoxication-alone or in combination with other drugs-was determined to be the cause of death by the responsible pathologist. All victims were young (24-37 years old) males, five of which had a well-documented history of drug abuse. Femoral blood concentration of furanylfentanyl ranged from 0.41 ng/g to 2.47 ng/g blood. Five cases presented a complex panel of drugs of abuse and prescription drugs. Moreover, in five cases the concurrent presence of pregabalin corroborates previous observations indicating pregabalin as a possible contributing factor in polydrug intoxications. We conclude that it is difficult to establish a specific lethal concentration of furanylfentanyl, due to incompletely known effects of possible pharmacokinetic and pharmacodynamic interactions with other drugs, as well as to the unknown degree of tolerance to opioids. We suggest that a full toxicological screening-to assess the possibility of drug interactions-together with segmental hair analysis regarding opioids-to estimate the level of opioid tolerance-be carried out to assist in the interpretation of cases involving synthetic opioids such as furanylfentanyl.

  • 5.
    Holmgren, Per
    et al.
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Carlsson, Björn
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Zackrisson, Anna-Lena
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Lindblom, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Forensic Genetics. Linköping University, Faculty of Health Sciences.
    Dahl, Marja-Liisa
    Department of Medical Sciences, Clinical Pharmacology, University Hospital, Uppsala, Sweden.
    Scordo, Maria Gabriella
    Department of Medical Laboratory Sciences and Technology, Division of Clinical Pharmacology, Karolinska Institutet, University Hospital, Stockholm, Sweden.
    Druid, Henrik
    National Board of Forensic Medicine and Department of Forensic Medicine, Karolinska Institutet, Solna, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Enantioselective analysis of citalopram and its metabolites in postmortem blood and genotyping for CYD2D6 and CYP2C192004In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 28, no 2, p. 94-104Article in journal (Refereed)
    Abstract [en]

    Citalopram, a selective serotonin reuptake inhibitor, is one of the most commonly found drugs in Swedish forensic autopsy cases. Citalopram is a racemic drug with 50:50 of the S- and R- enantiomers. Enantioselective analysis of citalopram and its metabolites desmethylcitalopram and didesmethylcitalopram were performed in femoral blood from 53 autopsy cases by a chiral high-performance liquid chromatography (HPLC) method. The mean (± standard deviation) S/R ratio for citalopram was 0.67 ± 0.25 and for desmethylcitalopram, 0.68 ± 0.20. We found increasing S/R ratios with increasing concentrations of citalopram. We also found that high citalopram S/R ratios were associated with a high parent drug-to-metabolite ratio and may be an indicator of recent intake. Citalopram is metabolized by cytochrome P450 (CYP) 3A4, 2C19, and 2D6. Genotyping for the polymorphic CYP2C19 and CYP2D6 revealed no poor metabolizers regarding CYP2C19 and only 2 (3.8%) poor metabolizers regarding CYP2D6. The presence of drugs metabolized by and/or inhibiting these enzymes in several of the cases suggests that such pharmacokinetic interactions are a more important (practical) problem than metabolic deficiency. Enantioselective analysis of citalopram and its metabolites can provide additional information when interpreting forensic toxicology results and might be a necessity in the future.

  • 6.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry.
    Elimination half-life of acetone in humans: Case reports and review of the literature2000In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 24, no 1Article in journal (Refereed)
    Abstract [en]

    Two instances of finding abnormally high concentrations of acetone in urine (0.10 g/dL and 0.052 g/dL) without any measurable amounts of ethanol (< 0.005 g/dL) or isopropanol (< 0.005 g/dL) prompted a survey of the elimination kinetics of isopropanol and its metabolite acetone in humans. In a hospital patient who had ingested denatured alcohol, the elimination half- life (t( 1/2 )) of acetone during detoxification was 27 h and not 3-5 h as reported by other workers. Several other literature reports of individuals who had ingested isopropanol as well as controlled studies after administration of moderate amounts of acetone and/or isopropanol support the notion of a long elimination half-life of 17-27 h for acetone compared with a t( 1/2 ) of 1-3 h for isopropanol.

  • 7.
    Jones, A Wayne
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Forensic Drug Profile: Cocaethylene2019In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 43, no 3, p. 155-160Article, review/survey (Refereed)
    Abstract [en]

    This article is intended as a brief review or primer about cocaethylene (CE), a pharmacologically active substance formed in the body when a person co-ingests ethanol and cocaine. Reference books widely used in forensic toxicology contain scant information about CE, even though this cocaine metabolite is commonly encountered in routine casework. CE and cocaine are equi-effective at blocking the reuptake of dopamine at receptor sites, thus reinforcing the stimulant effects of the neurotransmitter. In some animal species, the LD50 of CE was lower than for cocaine. CE is also considered more toxic to the heart and liver compared with the parent drug cocaine. The plasma elimination half-life of CE is similar to 2 h compared with similar to 1 h for cocaine. The concentrations of CE in blood after drinking alcohol and taking cocaine are difficult to predict and will depend on the timing of administration and the amounts of the two precursor drugs ingested. After an acute single dose of cocaine and ethanol, the concentration-time profile of CE runs on a lower level to that of cocaine, although CE is detectable in blood for several hours longer. A strong case can be made for adding together the concentrations of cocaine and CE in forensic blood samples when toxicological results are interpreted in relation to acute intoxication and the risk of an overdose death.

  • 8.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry.
    Heroin use by motorists in Sweden confirmed by analysis of 6-acetylmorphine in urine [1]2001In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 25, no 5, p. 353-355Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 9.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Impact of JAT publications 1981-2003: The most prolific authors and the most highly cited articles2004In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 28, no 7, p. 541-545Article in journal (Refereed)
    Abstract [en]

    The Journal of Analytical Toxicology (JAT) recently celebrated its 25th anniversary as an international periodical devoted to publishing scholarly articles in the field of analytical and forensic toxicology. Over the years many important papers spanning the entire field of chemical toxicology have appeared in JAT. One way to assess the usefulness of these papers is by looking at the number of times they subsequently become cited in the reference lists of papers published in other peer-reviewed journals including JAT itself (self-citations). The Thomson Institute for Scientific Information (ISI), headquartered in Philadelphia, PA, has produced a citation database containing all JAT articles published between 1981 through 2003 (N = 2254). This database was used to gather information about the most prolific authors of articles appearing in JAT, the most highly cited articles, the inter-relationships between co-authors, and the countries where the work originated. The person listed most frequently as an author was E.J. Cone, who authored or co-authored 69 papers that attracted a total of 1432 citations, giving a citation impact of 20.76. However, the most highly cited article in JAT was a solo-author work from 1981 by M.E. Jolley describing a fluorescence polarization immunoassay for the analysis of therapeutic drugs in plasma, which was cited 184 times. Working and writing in teams can boost the output of scientific articles as exemplified by the Institut de Médecine Légale in Strasbourg with P. Kintz as the driving force. Kintz and his associates produced the most collaborative work published in JAT. Citation analysis is being increasingly used to evaluate the importance of scientific articles and the journals where these works are published (e.g., impact factors). This article has identified JAT's scientific elite as evidenced by the most prolific authors and the most highly cited papers.

  • 10.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry.
    JAT's impact factor: Room for improvement?2002In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 26Article in journal (Refereed)
  • 11.
    Jones, A Wayne
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Letter: Elimination half-lives of benzoylecgonine and MDMA in an apprehended driver2008In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 32, no 2, p. 197-198Article in journal (Other academic)
    Abstract [en]

    n/a

  • 12.
    Jones, A Wayne
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Letter: Hirsch-index for winners of TIAFT's mid-career achievement award2008In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 32, no 4, p. 327-328Article in journal (Other academic)
  • 13.
    Jones, A Wayne
    Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Linköping University, Faculty of Health Sciences.
    Letter to the editor: Body mass index and blood-alcohol calculations2007In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 31, no 3, p. 177-178Article in journal (Other academic)
    Abstract [en]

    Alcohol tops the list of psychoactive substances encountered in police investigations of crimes such as mugging, murder, sexual assault, and especially impaired driving. Accordingly, the need often arises to interpret a person`s blood-alcohol concentration (BAC) in relation to the degree of alcohol influence and the amount of alcohol consumed. Such calculations are usually done with the aid of so-called “know your limit” or blood-alcohol charts, and more recently, several computer programs have been developed for this purpose.

  • 14.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry.
    Reference limits for urine/blood ratios of ethanol in two successive voids from drinking drivers2002In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 26, no 6, p. 333-339Article in journal (Refereed)
    Abstract [en]

    Specimens of venous whole blood and two successive urinary voids were collected from 450 individuals apprehended for driving under the influence of alcohol in Sweden. The first specimen of urine (UAC-1) was obtained as soon as possible after arrest, and the second void (UAC-2) was collected about 60 min later (mean 66 min, range 30-130). A specimen of venous blood was drawn approximately 30 min after the first urine sample was collected. Ethanol was determined in blood and urine by headspace gas chromatography, a method with high analytical precision (coefficient of variation ~1%). The mean UAC for the first void was 2.60 g/L (range 0.21-5.35) compared with 2.40 g/L (range 0.16-5.50) in the second void. The mean concentration of alcohol in venous blood (BAC) was 1.97 g/L (range 0.08-4.57). The concentrations of ethanol in the two voids of urine were highly correlated (r = 0.97, residual standard deviation [SD] 0.22 g/L). The UAC and BAC results were also highly correlated, r = 0.958 (residual SD 0.28 g/L) for the first void and r = 0.978 (residual SD 0.21 g/L) for the second void. The concentration of ethanol in the first void (UAC-1) was higher than the second void (UAC-2) in 383 (87%) instances, decreasing by 0.23 g/L/h on average. In 57 instances (13%), UAC-1 was less or equal to UAC-2 with a mean increase of 0.19 g/L. When BAC exceeded 0.5 g/L (N = 429), the mean UAC-1/BAC ratio was 1.345 with 95% reference limits of 0.968 and 1.72, which agreed well with median (2.5th and 97.5th percentiles) of 1.325 (0.938 and 1.79). For the second void, the mean UAC-2/BAC ratio was 1.221 with 95% reference limits of 0.988 and 1.45 and with a median (2.5th and 97.5th percentiles) of 1.226 (0.997 and 1.46). These reference limits are appropriate to use when a person's venous BAC needs to be estimated with reasonable scientific certainty from the concentration determined in specimens of urine.

  • 15.
    Jones, A Wayne
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Review of Caffeine-Related Fatalities along with Postmortem Blood Concentrations in 51 Poisoning Deaths2017In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 41, no 3, p. 167-172Article, review/survey (Refereed)
    Abstract [en]

    Publications reporting concentrations of caffeine in postmortem blood were reviewed if the cause of death was attributed to overdosing (poisoning) with drugs. Age and gender of the deceased, the manner of death (accident, suicide or undetermined) and types of co-ingested drugs were evaluated in relation to the concentrations of caffeine in blood (N = 51). The mean age (+/- SD) of the victims was 39 +/- 17.8 years (range 18-84 years) and most were female (N = 31 or 61%). The difference in mean age ofmales (42 +/- 17.2 years) and females (37 +/- 18.3 years) was not statistically significant (t = 0.811, P = 0.421). The mean (+/- SD), median and range of caffeine concentrations in postmortem blood were 187 +/- 96mg/L (180mg/L) and 33-567mg/L, respectively. The median concentration of caffeine in males (161mg/L) was not significantly different from that of females (182mg/L), z = 1.18, P = 0.235. There was no correlation between the age of the deceased and the concentration of caffeine in postmortem blood (R-2 = 0.026, P amp;gt; 0.05). Manner of death was classified as suicide in 51% of cases (median blood-caffeine 185mg/L), accidental in 16% (median 183mg/L) or undetermined in 33% (median 113mg/L). The median concentration of caffeine in blood was lower when manner of death was undetermined compared with suicide or accidental (P = 0.023). Although other drugs, including ethanol, antidepressants, antipsychotics, benzodiazepines and/or ephedrine, were often identified in postmortem blood, the predominant psychoactive substance was caffeine. The deceased had ingested caffeine in tablet or powder form and it does not seem likely that toxic concentrations of caffeine can be achieved from over-consumption of caffeinated beverages alone.

  • 16.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry.
    Time-adjusted urine/blood ratios of ethanol in drinking drivers [1]2003In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 27, no 3, p. 167-168Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 17.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Eklund, A.
    National Board for Forens Medicine.
    Kronstrand, Robert
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Concentration-Time Profiles of Gamma-Hydroxybutyrate in Blood After Recreational Doses are Best Described by Zero-Order Rather Than First-Order Kinetics2009In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 33, no 6, p. 332-335Article in journal (Refereed)
    Abstract [en]

    The recreational drug gamma-hydroxybutyrate (GHB) has a short plasma elimination half-life (t(1/2)) reported to be about 30-50 min. However, this represents a terminal half-life and therefore might not necessarily apply after large (abuse) doses are taken. Clinical studies with sodium oxybate (sodium salt of GHB) suggest that zero-order rather than first-order kinetics are more appropriate to describe post-peak concentration-time (C-T) profiles. We report the case of a 23-year-old male found unconscious by the police and a blood sample contained 100 mg/L GHB and 0.14 g% ethanol. On regaining consciousness the man admitted drinking alcohol about 6 h earlier but claimed that his drink must have been spiked with GHB. The police wanted to know how much GHB had been administered to account for the man's clinical condition. A back-calculation for 6 h, assuming a GHB half-life of 40 min, gives a very high concentration in blood of approximately 900 mg/L, which would probably have proven fatal. Back-calculating using zero-order kinetics and a proposed elimination rate of 18 mg/L per hour leads to a GHB concentration of 208 mg/L, which is much more realistic. Toxicologists should not arbitrarily apply the principles of first-order kinetics after abuse doses of drugs, when zero-order or saturation kinetics (Michaelis-Menten) are more appropriate.

  • 18.
    Jones, A Wayne
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Gladh, Sven-Ake
    National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Norup Windberg, Charlotte
    University of Copenhagen, Denmark.
    Stybe Johansen, Sys
    University of Copenhagen, Denmark.
    Stability of gamma-Hydroxybutyrate in Blood Samples from Impaired Drivers after Storage at 4A degrees C and Comparison of GC-FID-GBL and LC-MS-MS Methods of Analysis2015In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 39, no 4, p. 294-299Article in journal (Refereed)
    Abstract [en]

    The stability of gamma-hydroxybutyrate (GHB) was determined in 50 blood samples from impaired drivers after storage at 4A degrees C for up to 12 months. GHB was determined in whole blood by gas chromatography-flame ionization detector (GC-FID) after conversion into gamma-butyrolactone (GBL) and results were compared with LC-MS-MS. Both analytical methods showed a linear response (R-2 greater than 0.99) to GHB concentrations from 2 to 250 mg/kg. The mean decrease in concentration after storage was 4.8 mg/kg, with extreme changes of +13 mg/kg or -29 mg/kg. Results by the GC-FID-GBL method (y-variate) and the LC-MS-MS method (x-variate) were highly correlated (R-2 = 0.974). The regression equation was y = 0.85x + 2.2 and residual standard deviation (SD) was 7.8 mg/kg. The y-intercept (2.2 mg/kg) was not significantly different from zero (P greater than 0.05), although the slope of the regression line (0.85) differed from unity (P less than 0.001), indicating a proportional bias of 15%. The LC-MS-MS method tended to give higher results than the GC-FID-GBL method. The mean difference (bias) was 12 mg/kg (P less than 0.001). The SD of individual differences was 11.3 mg/kg and 95% limits of agreement were -11 to +33 mg/kg. The results of this study show that concentrations of GHB in whole blood are stable during storage at 4A degrees C for up to 6 months.

  • 19.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Holmgren, A
    National Board for Forensic Medicine, Sweden .
    Concentration Ratios of Methamphetamine to Amphetamine in Blood Can Help to Distinguish Use of Methamphetamine from Various Mixtures of the Two Stimulants2012In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 36, no 9, p. 634-637Article in journal (Refereed)
    Abstract [en]

    Using a forensic toxicology database, the authors investigated cases of driving under the influence of drugs (DUID) if methamphetamine (MA) was identified in the blood samples (N 9,310). The concentrations of MA and amphetamine (AM) in blood were determined after liquidliquid extraction by gas chromatographymass spectrometry at limits of quantitation of 0.03 mg/L for both stimulants. In 814 cases, AM was negative in blood and MA was positive at mean (median) and highest concentrations of 0.19 mg/L (0.11 mg/L) and 3.4 mg/L, respectively. Both amines were present in blood in 8,496 cases at concentrations of 0.54 mg/L (0.35 mg/L) and 10.4 mg/L for AM and 0.41 mg/L (0.22 mg/L) and 5.6 mg/L for MA. However, the correlation between AM and MA was low and insignificant (r 0.13) in the whole material. The coefficient of correlation increased to r 0.41 (P 0.001) when the MA/AM concentration ratio was 1. When MA/AM ratios were selected at intervals of 1.0 (e.g., 3.0 and 4.0 up to 9.0 and 10.0), the correlation between AM and MA was r 0.99 (P 0.001). Such cases represent the use of MA without contamination from AM, and the mean (median) and highest concentrations of this secondary amine in blood of DUID suspects were 0.72 mg/L (0.56 mg/L) and 4.2 mg/L, respectively.

  • 20.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Holmgren, A
    Kugelberg, FC
    Gamma-hydroxybutyrate concentrations in the blood of impaired drivers, users of illicit drugs, and medical examiner cases2007In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 31, no 9, p. 566-572Article in journal (Refereed)
    Abstract [en]

    Gamma-hydroxybutyrate (GHB) was determined in blood samples from impaired drivers, people arrested for petty drug offenses (non-traffic cases), and GHB-related deaths. The method of analysis involved conversion of GHB into gamma-butyrolactone and determination of the latter by gas chromatography with a flame ionization detector, and with gamma-valerolactone as the internal standard. The mean and median concentrations of GHB in blood from impaired drivers (N = 473) were 90 and 84 mg/L, respectively, and offenders were predominantly men (96%) with an average age of 26 year (range 15-50 year). In 185 cases, GHB was the only drug present in blood at mean and median concentrations of 92 and 86 mg/L, respectively. People arrested for petty drug offenses (N = 1061) had slightly higher GHB concentrations in their blood: median 118 mg/L for men and 111 mg/L for women. In GHB-related deaths (N = 33), the mean and median concentrations were considerably higher: 307 mg/L and 190 mg/L, respectively, and the highest was 2200 mg/L. The typical signs of drug influence noted by the arresting police officers included sedation, agitation, slurred speech, irrational behaviour, jerky movements, and spitting. The short elimination half-life of GHB means that the concentrations in blood decrease rapidly and are probably a lot lower than at the time of driving, which was 30-90 min earlier.

  • 21.
    Jones, A Wayne
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Holmgren, A.
    Natl Board Forens Toxicol, Div Forens Toxicol, S-58758 Linkoping, Sweden.
    Kugelberg, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Toxicol, Div Forens Toxicol, S-58758 Linkoping, Sweden.
    Busardo, F. P.
    Sapienza Univ Rome, Italy.
    Relationship Between Postmortem Urine and Blood Concentrations of GHB Furnishes Useful Information to Help Interpret Drug Intoxication Deaths2018In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 42, no 9, p. 587-591Article in journal (Refereed)
    Abstract [en]

    This article reports the concentrations of gamma-hydroxybutyrate (GHB) in femoral blood and bladder urine in a case series of drug intoxication deaths (N = 37). GHB was determined in blood (B-GHB) and urine (U-GHB) by a GC-FID-GBL method and 30 mg/L was used as a cut-off concentration for reporting positive results. The mean (median) and range of GHB concentrations in bladder urine were 2,818 mg/L (1,900 mg/L) and 120-13,000 mg/L, respectively. These concentrations were appreciably higher than those in femoral blood, 637 mg/L (260 mg/L) and 30-9,200 mg/L, respectively. Urine/blood ratios of GHB were highly variable (mean 8.99, median 5.33 and range 0.16-29.3). GHB is rapidly metabolized and cleared from the bloodstream, whereas there is no metabolism occurring in the urinary bladder. In five autopsy cases, U-GHB was lower than B-GHB, which suggests that these individuals died before equilibration of the drug in all body fluids and tissues. In the other 32 deaths, U-GHB was higher than B-GHB, sometimes appreciably higher, which points towards a longer survival time after intake or administration of GHB. The analysis of urine extends the window of detection of GHB by several hours compared with blood samples, depending in part on when the bladder was last voided before death. Furthermore, the urinary concentration of GHB gives a hint about the concentration in blood during the time that the urine was produced in the kidney and stored in the bladder since the previous void.

  • 22.
    Jones, A Wayne
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Holmgren, Anita
    Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, SE-58758 Linkoping, Sweden .
    Concentrations of Cocaine and Benzoylecgonine in Femoral Blood from Cocaine-Related Deaths Compared with Venous Blood from Impaired Drivers2014In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 38, no 1, p. 46-51Article in journal (Refereed)
    Abstract [en]

    The concentrations of cocaine and its major metabolite benzoylecgonine (BZE) were determined in femoral blood from 132 cocaine-related deaths and compared with venous blood from 988 apprehended drivers. Cocaine and BZE were determined by solid-phase extraction and isotope dilution gas chromatographymass spectrometry with limits of quantitation of 0.02 mg/L for both substances. Significantly more men (9598) than women (25) abused cocaine, although their mean age was about the same (2930 years). Mean age (SD) of cocaine-related deaths was 29 7 years, which was not significantly different from 30 8 years in traffic cases (P 0.05). The median concentration of cocaine in blood in 61 fatalities was 0.10 mg/L compared with 0.06 mg/L in traffic cases (P 0.001). In drug intoxication deaths, the median concentration of cocaine was 0.13 mg/L (N 25), which was not significantly different from 0.09 mg/L (N 36) in other causes of death. Cocaine-related deaths mostly involved mixed drug intoxications including co-ingestion of heroin, cannabis, amphetamines as well as legal drugs, such as benzodiazepines and/or ethanol. The concentrations of cocaine in blood from living and deceased persons overlapped, which makes it infeasible to predict toxicity from the analytical toxicology results alone.

  • 23.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Holmgren, Anita
    Nationall Board of Forensic Medicine.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Blood Methadone Concentrations in Living and Deceased Persons: Variations Over Time, Subject Demographics, and Relevance of Coingested Drugs2012In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 36, no 1, p. 12-18Article in journal (Refereed)
    Abstract [en]

    n/a

  • 24.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Holmgren, Anita
    Department of Forensic Genetics and Forensic Toxicology National Board of Forensic Medicine, Linköping.
    Kugelberg, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology.
    Driving under the influence of opiates: Concentration relationships between morphine, codeine, 6-acetyl morphine, and ethyl morphine in blood2008In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 32, no 4, p. 265-272Article in journal (Refereed)
    Abstract [en]

    Morphine and codeine are frequently identified in blood samples from impaired drivers. But whether these opiates reflect the use of prescription analgesics or abuse of the illicit drug heroin (diacetyl morphine) is not always obvious. Opiates, either alone or together with other drugs, were determined in 2573 blood specimens from impaired drivers by sensitive and specific methods of analysis. The specific metabolite of heroin 6-acetyl morphine (6-AM) was quantifiable in only 52 cases (2%) at mean, median, and highest concentrations of 0.015, 0.010, and 0.10 mg/L, respectively. The mean, median, and highest concentrations of morphine were 0.046, 0.03, and 1.13 mg/L, respectively (N = 2029). The corresponding concentrations of codeine (N = 1391) were 0.047, 0.01, and 2.40 mg/L. Ethyl morphine was identified in 63 cases at a mean concentration of 0.055 mg/L (median 0.03 mg/L). When 6-AM was present in urine (N = 324), the mean morphine/codeine ratio in blood was 7.5 (median 6.7), and this important ratio was less than unity in only two cases. This study finds compelling evidence that ∼90% of apprehended drivers in Sweden with morphine and codeine in their blood had used heroin.

  • 25.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry.
    Hylén, L
    Svensson, E
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Helander, A
    Storage of specimens at 4°C or addition of sodium fluoride (1%) prevents formation of ethanol in urine inoculated with Candida albicans1999In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 23, p. 333-336Article in journal (Refereed)
  • 26.
    Kronstrand, Robert
    et al.
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology. Linköping University, Faculty of Health Sciences.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology. Linköping University, Faculty of Health Sciences.
    Dizdar (Dizdar Segrell), Nil
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Faculty of Health Sciences.
    Larsson, Göran
    Sahlgrenska University Hospital, Department of Clinical Chemistry and Transfusion Medicine, Göteborg, Sweden.
    Quantitative Analysis of Desmethylselegiline, Methamphetamine, and Amphetamine in Hair and Plasma from Parkinson Patients on Long-Term Selegiline Medicatio2003In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 27, no 3, p. 135-141Article in journal (Refereed)
    Abstract [en]

    Hair and plasma from patients on long-term selegiline medication were analyzed to evaluate the relationships between plasma and hair melanin concentrations and the incorporation of the selegiline metabolites methamphetamine and amphetamine in hair, and to evaluate hair analyses for determining compliance in medication. Analyses were performed on both the whole hairs, as well as pigmented and non-pigmented hairs from gray-haired patients. Melanin was quantitated by spectrophotometry, and metabolites were quantitated by gas chromatography-mass spectrometry. Concentrations in pigmented and non-pigmented hairs differed significantly for both methamphetamine (p < 0.01) and amphetamine (p < 0.02), with mean concentration ratios being 3.69 ± 1.88 and 2.95 ± 1.16 for methamphetamine and amphetamine, respectively. Segmental analysis indicated that some patients had not been compliant with medication. We concluded that the incorporation of methamphetamine and amphetamine into hair of single individuals shows a preference for pigmented hairs over white hairs and that segmental analysis of hair may he useful when measuring compliance with medication.

  • 27.
    Kronstrand, Robert
    et al.
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Andersson, Maria Choi
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Larson, Göran
    Sahlgrenska University Hospital, Department of Clinical Chemistry and Transfusion Medicine, Göteborg, Sweden.
    Incorporation of Selegiline Metabolites into Hair after Oral Selegiline Intake2001In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 25, no 7, p. 594-601Article in journal (Refereed)
    Abstract [en]

    We have previously shown that melanin in human hair has a great impact on the incorporation of codeine into hair. The present study on 10 subjects was performed to investigate whether or not these findings could also be extrapolated to other therapeutic drugs. We chose selegiline because it metabolizes to two commonly abused central stimulants, methamphetamine and amphetamine. The results would therefore also be of interest when studying the intake of such drugs and their incorporation into human hair. Selegiline and metabolites were determined by gas chromatography-mass spectrometry, total melanin by spectrophotometry, and pyrroletricarboxylic acid by high-performance liquid chromatography with ultraviolet detection. Our results show strong positive exponential relationships (y = ex) between melanin and the metabolites, which for methamphetamine improved by normalizing for plasma area under the curve. We conclude that the major metabolites of selegiline can be detected in hair up to four weeks after a single oral dose and that the incorporation closely relates to the melanin contents.

  • 28.
    Kronstrand, Robert
    et al.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Jones, A Wayne
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Concentration Ratios of Codeine-to-Morphine in Plasma after a Single Oral Dose (100 mg) of Codeine Phosphate2001In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 25, no 6, p. 486-487Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 29.
    Kronstrand, Robert
    et al.
    RMV Linköping.
    Nyström, Ingrid
    RMV Linköping.
    Andersson, Malin
    RMV Linköping.
    Gunnarsson, Lina
    RMV Linköping.
    Hägg, Staffan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Josefsson, Martin
    RMV Linköping.
    Ahlner, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology .
    Urinary Detection Times and Metabolites/Parent Compound ratios After a Single Dose of Buprenorphine2008In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 32, no 8, p. 586-593Article in journal (Refereed)
    Abstract [en]

       

  • 30.
    Kronstrand, Robert
    et al.
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Nyström, Ingrid
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Josefsson, Martin
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Hodgins, Sheilagh
    Department of Psychology, Université de Montréal, Québec, Canada.
    Segmental Ion Spray LC-MS-MS Analysis of Benzodiazepines in Hair of Psychiatric Patients2002In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 26, no 7, p. 479-484Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to develop a liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for the analysis of benzodiazepines in human hair. The method was tested by analyzing hair samples from forensic and clinical psychiatric patients where benzodiazepines had been prescribed during hospitalization and after care. Hair samples were obtained at discharge from the clinic and then after six months. Two-centimeter segments of the hair samples (10–30 mg) were washed once with isopropanol, three times with phosphate buffer, and again with isopropanol, dried, weighed, and digested with proteinase K before solid-phase extraction with BondElut Certify columns. Diazepam, nordiazepam, oxazepam, alprazolam, OH-alprazolam, nitrazepam, 7-aminonitrazepam, flunitrazepam, 7-aminoflunitrazepam, clonazepam, and 7-aminoclonazepam were quantitated in MRM mode using one transition for each analyte and deuterated internal standard. The calibration range was 0.125–5 ng/mg for diazepam, nordiazepam, and oxazepam and 0.025–1.0 ng/mg for the other compounds. In the hair samples analyzed, diazepam, flunitrazepam, nitrazepam, and clonazepam was detected together with their metabolites. Alprazolam was not detected in any sample. Segmental hair analysis revealed differences in drug deposition in hair before and after release from psychiatric treatment. Both increases and decreases of hair drug concentrations were seen after release even though the prescribed dose was the same. This was taken as an indication of noncompliance during the after-care period. We conclude that the extraction and LC-MS-MS procedures were adequate to detect benzodiazepines in hair and that the results indicated that segmental hair analysis might provide retrospective information about medication intake.

  • 31.
    Kronstrand, Robert
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Roman, Markus
    Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Andersson, Mikael
    Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Eklund, Arne
    Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Toxicological Findings of Synthetic Cannabinoids in Recreational Users2013In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 37, no 8, p. 534-541Article in journal (Refereed)
    Abstract [en]

    In recent years, several synthetic cannabinoid compounds have become popular recreational drugs of abuse because of their psychoactive properties. This paper presents toxicological findings of synthetic cannabinoids in whole blood from some cases of severe intoxication including quantitative data from recreational users and a fatal intoxication. Samples were analyzed by liquid chromatography-tandem mass spectrometry in a scheduled multiple reaction mode after a basic liquid extraction. Twenty-nine synthetic cannabinoids were included in the method. In our data set of similar to 3000 cases, 28% were found positive for one or more synthetic cannabinoid(s). The most common finding was AM-2201. Most of the analytes had median concentrations of andlt;0.5 ng/g in agreement with other published data. The emerging drugs MAM-2201 (n = 151) and UR-144 (n = 181) had mean (median) concentrations of 1.04 (0.37) and 1.26 (0.34), respectively. The toxicity of the synthetic cannabinoids seems to be worse than that of natural cannabis, probably owing to the higher potency and perhaps also to the presence of several different cannabinoids in the smoked incense and the difficulties of proper dosing. The acute toxic effects may under certain circumstances contribute to death.

  • 32.
    Kronstrand, Robert
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Roman, Markus
    Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Dahlgren, Maria
    Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Thelander, Gunilla
    Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Wikström, Maria
    Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Druid, Henrik
    Department of Forensic Medicine, National Board of Forensic Medicine, Linköping, Sweden;Department of Oncology–Pathology, Karolinska Institutet, Stockholm, Sweden.
    A Cluster of Deaths Involving 5-(2-Aminopropyl)Indole(5-IT)2013In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 37, no 8, p. 542-546Article in journal (Refereed)
    Abstract [en]

    During 2012, the designer drug 5-(2-aminopropyl)indole emerged in Sweden, and became available at different web sites under the name 5-IT or 5-API. This compound is an indole derivative and a positional isomer of alpha-methyltryptamine. In this paper, we report the pathology and toxicology from 15 deaths involving 5-IT. Routine postmortem toxicology was performed in femoral blood, using a targeted screening for pharmaceuticals and drugs of abuse with liquid chromatography time-of-flight technology, and positive results were quantified using chromatographic techniques. For 5-IT, a new method was developed using ultra-high-performance liquid chromatography and tandem mass spectrometry. In 11 cases, intoxication was the cause of death. Two cases were signed out as causa ignota, and they were considered to be natural deaths. All determinations of 5-IT were performed in femoral blood and the concentrations ranged from 0.7 to 18.6 mg/g. Two cases had 5-IT as the only drug identified, while the others presented with other psychotropic drugs or medications in the blood as well. Shortly after this series of deaths, 5-IT was scheduled as a hazardous substance according to the regulation Certain Goods Dangerous to Health on 18 September 2012 prohibiting the handling and selling of the drug. Since then, no positive cases have been found.

  • 33.
    Kronstrand, Robert
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linköping, Sweden.
    Roman, Markus
    National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linköping, Sweden.
    Thelander, Gunilla
    National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linköping, Sweden.
    Eriksson, Anders
    Section of Forensic Medicine, Department of Community Medicine and Rehabilitation, Umeå University, Umeå, Sweden.
    Unintentional Fatal Intoxications with Mitragynine and O-Desmethyltramadol from the Herbal Blend Krypton2011In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 35, no 4, p. 242-247Article in journal (Refereed)
    Abstract [en]

    The leaves of Kratom, a medicinal plant in Southeast Asia, have been used as an herbal drug for a long time. At least one of the alkaloids present in Kratom, mitragynine, is a mu-receptor agonist. Both Kratom and an additional preparation called Krypton are available via the internet. It seems to consist of powdered Kratom leaves with another mu-receptor agonist, O-desmethyltramadol, added. O-Desmethyltramadol is an active metabolite of tramadol, a commonly prescribed analgesic.We present nine cases of intoxication, occurring in a period of less than one year, where both mitragynine and O-desmethyltramadol were detected in the postmortem blood samples. Neither tramadol nor N-desmethyltramadol was present in these samples, which implies that the ingested drug was O-desmethyltramadol. The blood concentrations of mitragynine, determined by ultra-performance liquid chromatography-tandem mass spectrometry, ranged from 0.02 to 0.18 µg/g, and O-desmethyltramadol concentrations, determined by gas chromatography with nitrogen-specific detection, ranged from 0.4 to 4.3 µg/g. We believe that the addition of the potent mu-receptor agonist O-desmethyltramadol to powdered leaves from Kratom contributed to the unintentional death of the nine cases presented and conclude that intake of Krypton is not as harmless as it often is described on internet websites.

  • 34.
    Kronstrand, Robert
    et al.
    National Board of Forensic Medicine.
    Roman, Markus
    National Board of Forensic Medicine.
    Thelander, Gunilla
    National Board of Forensic Medicine.
    Eriksson, Anders
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Forensic Medicine.
    Unintentional fatal intoxications with mitragynine and O-Desmethyltramadol from the herbal blend krypton2011In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 35, no 4, p. 242-247Article in journal (Refereed)
    Abstract [en]

    The leaves of Kratom, a medicinal plant in Southeast Asia, have been used as an herbal drug for a long time. At least one of the alkaloids present in Kratom, mitraynine, is a mu-receptor agonist. Both Kratom and an additional preparation called Krypton are available via the internet. It seems to consist of powdered Kratom leaves with another mu-receptor agonist, O-desmethyltramadol added. O-desmethyltramadol is an acitve metabolite of tramadol, a commonly prescribed analgesic. We present nine cases of intoxication, occurring in a period of less than one year, where both mitragynine and O-desmethyltramadol were detected in the postmortem blood samples. neither tramadol nor N-desmethyltramadol was present in these samples, which implies that the ingested drug was O-desmethyltramadol. The blood concentrations of mitragynine, determined by ultra-performance liquid chromatography-tandem mass spectrometry, ranged from 0.02 to 0.18 μg/g, and O-desmethyltramadol concentrations, determined by gas chromatogtraphy with nitrogen-specific detection, ranged from 0.4 to 4.3 μg/g. We believe that the addition of the potent mu-receptor agonist O-desmethyltramadol to powdered leaves from Kratom contributed to the unintentional death of the nine cases presented and conclude that intake of Krypton is not as harmless as it often is described on internet websites.  

  • 35.
    Kronstrand, Robert
    et al.
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences.
    Seldén, Tor
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Josefsson, M
    National Board Forensic Medicine .
    Analysis of buprenorphine, norbuprenorphine, and their glucuronides in urine by liquid chromatography-mass spectrometry2003In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 27, no 7, p. 464-470Article in journal (Refereed)
    Abstract [en]

    Buprenorphine is used for the treatment of chronic pain and also in treatment of heroin addiction as an alternative to methadone. As the availability of buprenorphine increases, so does the risk for abuse and the pressure on forensic and clinical laboratories to analyze for it. Buprenorphine and its dealkylated metabolite are excreted in urine, almost exclusively as glucuronides. The aim of the present study was to evaluate electrospray liquid chromatography tandem mass spectrometry (LC-MS-MS) for the rapid screening and quantitation of buprenorphine and its metabolites in urine. Three approaches were evaluated: (1) direct injection of diluted urine for measurement of glucuronides, (2) direct injection of diluted urine after enzymatic hydrolysis for the quantitation of buprenorphine and norbuprenorphine, and (3) quantitation of buprenorphine and norbuprenorphine after enzymatic hydrolysis and solid-phase extraction (SPE). One hundred six samples were subjected to procedure 1 and, when positive, further quantitated using procedure 2. Only samples with low analyte concentrations (< 20 microg/L) were subject to SPE. Concentrations of buprenorphine and norbuprenorphine in patients (N = 16) ranged between 31 and 1080 microg/L and 48-2050 microg/L, respectively. In suspected abusers (N = 33), the ranges were 2.3-796 microg/L and 5.0-2580 microg/L. In four of the authentic samples, both the buprenorphine and norbuprenorphine concentrations were below the 20- micro g/L cutoff. We concluded that LC-MS-MS analysis of the glucuronides provided an adequate screening method, but that the direct method for quantitation sometimes had to be complemented with a concentration by SPE, providing increased sensitivity, thus lowering the cutoff from 20 to 1 microg/L urine.

  • 36.
    Kronstrand, Robert
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. National Board of Forensic Medicine, Linköping, Sweden.
    Thelander, G.
    National Board of Forensic Medicine, Linköping, Sweden.
    Lindstedt, D.
    National Board of Forensic Medicine, Linköping, Sweden.
    Roman, M.
    National Board of Forensic Medicine, Linköping, Sweden.
    Kugelberg, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. National Board of Forensic Medicine, Linköping, Sweden.
    Fatal intoxications associated with the designer opioid AH-79212014In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 38, no 8, p. 599-604Article in journal (Refereed)
    Abstract [en]

    AH-7921 (3,4-dichloro-N-[(1-dimethylamino) cyclohexylmethyl] benzamide) is a designer opioid with similar to 80% of morphines m-agonist activity. Over a 6-month period, we encountered nine deaths where AH-7921 was involved and detected in blood from the deceased. Shortly after the last death, on August 1 2013, AH-7921 was scheduled as a narcotic and largely disappeared from the illicit market in Sweden. AH-7921 was measured by a selective liquid chromatography- MS-MS method and the concentrations of AH-7921 ranged from 0.03 to 0.99 mu g/g blood. Six of our cases had other drugs of abuse on board and most had other medications such as benzodiazepines, antidepressants and analgesics. However, the other medicinal drugs encountered were present in postmortem therapeutic concentrations and unlikely to have contributed to death. In addition to the parent compound, we identified six possible metabolites where two N-demethylated dominated and four mono-hydroxylated were found in trace amounts in the blood. In conclusion, deaths with AH-7921 seem to occur both at low and high concentrations, probably a result of different tolerance to the drug. Hence, it is reasonable to assume that no sharp dividing line exists between lethal and non-lethal concentrations. Further, poly-drug use did not seem to be a major contributing factor for the fatal outcome.

  • 37.
    Kugelberg, Fredrik
    et al.
    Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Druid, Henrik
    Division of Forensic Medicine, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Carlsson, Björn
    Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Ahlner, Johan
    Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Bengtsson, Finn
    Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Postmortem redistribution of the enantiomers of citalopram and its metabolites: an experimental study in rats2004In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 28, no 8, p. 631-637Article in journal (Refereed)
    Abstract [en]

    A rat model was used to study if postmortem redistribution of the S- and R-enantiomers of citalopram (CIT) and its metabolites demethylcitalopram (DCIT) and didemethylcitalopram (DDCIT) occurs after three different subcutaneous dosing procedures with racemic CIT. Two groups underwent chronic administration (20 mg/kg daily) using osmotic pumps. After 10 days, 1 of these groups received an acute-on-chronic drug challenge with a single injection of 100 mg/kg. The third group received the single 100 mg/kg dose only. Heart blood and brain samples were collected antemortem and 1, 3, or 24 h postmortem for enantioselective HPLC analysis. Increased postmortem blood drug and metabolite concentrations compared with corresponding antemortem concentrations were observed in all groups (p < 0.05 to p < 0.001). At 24 h after death, the ratios between postmortem and antemortem blood concentrations were around 3–4 for CIT as well as for the metabolites. In the brain, no major differences between antemortem and postmortem drug and metabolite concentrations were observed. The enantiomeric (S/R) concentrations ratios of CIT and metabolites in blood and brain were of similar magnitude before and after death. No differences between antemortem and postmortem parent drug-to-metabolite (P/M) ratios for CIT/DCIT in blood were observed. Finally, this animal model demonstrates that the S- and R-enantiomers of CIT and its metabolites were redistributed to the same extent postmortem.

  • 38.
    Kugelberg, Fredrik
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Kingbäck, Maria
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Carlsson, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Druid, H
    Rättsmedicin KI.
    Early-phase postmortem redistribution of the enantiomers of citalopram and its demethylated metabolites in rats2005In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 29, no 4, p. 223-228Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate the early-phase postmortem redistribution of the enantiomers of citalopram (CIT) and its metabolites demethylcitalopram (DCIT) and didemethylcitalopram (DDCIT) in a rat model. Furthermore, we wanted to examine the role of the lungs as a reservoir of postmortem drug release and to investigate the influence of storage temperature (21°C vs. 4°C) on postmortem changes. Rats were administered a single CIT dose of 100 mg/kg (s.c.), and heart blood and lung samples were collected antemortem and 15 min postmortem for enantioselective high-performance liquid chromatographic analysis. About three times higher blood drug and metabolite levels were observed in the postmortem rats than in the antemortem rats (p < 0.0001). Refrigeration at 4°C did not prevent, but significantly reduced, the postmortem increase in heart blood CIT levels as compared to the concentrations in the rats stored at 21°C (p < 0.05). The lung drug concentrations were lower postmortem than antemortem (p < 0.05). The enantiomeric (S/R) concentration ratios of CIT and metabolites in blood and lungs were of similar magnitude before and after death. The parent-drug-to- metabolite ratios for CIT/DCIT were unchanged after death. In conclusion, this study shows that heart blood CIT and metabolite levels increase rapidly after death. Further, a fall in postmortem CIT concentrations in the lungs was observed, indicating that the lungs seemed to represent one major source of drug release during early-phase postmortem redistribution.

  • 39.
    Lennestål, Roland
    et al.
    Umeå.
    Asplund, Cay
    Umeå.
    Nilsson, Mats
    Umeå.
    Lakso, Hans-Åke
    Umeå.
    Mjörndal, Tom
    Umeå.
    Hägg, Staffan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Serum levels of olanzapine in a non-fatal overdose2007In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 31, no 2, p. 119-121Article in journal (Refereed)
    Abstract [en]

    Olanzapine is a widely used second generation antipsychotic drug. Case reports of intoxications have been published, but reports in the literature of non-fatal intoxications of olanzapine containing repeated measurements of serum levels are scarce. Therefore, this case of non-fatal olanzapine intoxication is presented, in which 19 blood samples were drawn during 2 weeks. The highest (initial) measured value was estimated at 800 μg/L. This patient ingested 550 mg of olanzapine resulting in clinical signs of intoxication, including seizures. Because the patient was found the day after the intoxication, the initial concentration had probably been higher. The pharmacokinetics of olanzapine has been described as linear and dose-proportional throughout the therapeutic dosing range. Large overdoses, however, have been described to show non-linear pharmacokinetics. In this study's series of serum concentrations, a two-phase elimination was seen, with an initial elimination half-life of about 24 h during the first 3 days, followed by a second phase with a half-life of about 2.5 days. The patient in this case recovered completely. Because the elimination time after intoxication can be considerably longer than expected, it is recommended that the patient's serum concentrations after intoxication be monitored.

  • 40.
    Lennestål, Roland
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Lakso, Hans-Åke
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Nilsson, Mats
    Mjörndal, Tom
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Urine monitoring of diazepam abuse: new intake or not?2008In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 32, no 6, p. 402-407Article in journal (Refereed)
    Abstract [en]

    Testing for drugs-of-abuse in urine is requested for multiple reasons, including legal and workplace policies. Two cases were studied in which there was a suspicion that the patients continued to abuse diazepam, because of repeatedly positive urine samples. In these cases, diazepam metabolites were measured in urine samples by gas or liquid chromatography coupled to mass spectrometry. The concentrations of diazepam metabolites were subsequently creatinine correlated. Very long elimination times were found in the described cases. None of them had in fact ingested diazepam again during the study period. By the use of pharmacogenetic typing, one of the subjects was found to have a slow metabolism for CYP2C9 as well as for CYP2C19. In the second case, there was a possible drug interaction between diazepam and zolpidem.

  • 41.
    Nilsson, Gunnel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Kugelberg, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Kronstrand, Robert
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Quantitative Analysis of Zopiclone, N-desmethylzopiclone, Zopiclone N-oxide and 2-Amino-5-chloropyridine in Urine Using LC-MS-MS2014In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 38, no 6, p. 327-334Article in journal (Refereed)
    Abstract [en]

    A simple LC-MS/MS method was validated to allow determination of zopiclone (ZOP), Ndesmethylzopiclone (NDZOP), zopiclone N-oxide (ZOPNO) and 2-amino-5 chloropyridine (ACP) in urine at concentrations up to 3000 ng/mL within 3.5 min. This method was used for quantitative analysis of the analytes in authentic urine samples obtained 10 h after oral administration of zopiclone (Imovane®) and in aliquots of the same urine samples after different storage conditions. Additionally, pH of each studied urine sample was measured over time. The results showed that formation of ACP occurred at elevated pH and/or temperature by degradation of ZOP, NDZOP and ZOPNO. This method was also applied to samples obtained from two female victims of drug-facilitated assault. One sample had been exposed to long-term storage conditions at different temperatures and at pH>8.2, which resulted in high concentrations of ACP. The other sample, which was exposed to pH <6.5, showed no formation of ACP. ACP is formed both from ZOP and from its metabolites NDZOP and ZOPNO depending on the pH of the urine, time of storage and/or the temperature conditions. For correct interpretation in forensic cases ZOP, its major metabolites and ACP should be analyzed. When ACP is identified in urine the concentrations of ZOP, NDZOP and ZOPNO should be interpreted with great caution.

  • 42.
    Nordgren, Helena K
    et al.
    Karolinska Institutet.
    Holmgren, Per
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Liljeberg, Paula
    Karolinska Institutet.
    Eriksson, Nadja
    Karolinska Institutet.
    Beck, Olof
    Karolinska Institutet.
    Application of direct urine LC-MS-MS analysis for screening of novel substances in drug abusers2005In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 29, no 4, p. 234-239Article in journal (Refereed)
    Abstract [en]

    A newly developed liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was used to study 3000 human urine samples from 3 different populations for 23 analytes covering phenylethylamines, benzylpiperazine, and non-benzodiazepine hypnotics. Direct injection of urine and LC-MS-MS with rapid chromatography and atmospheric pressure chemical ionization was used in the screening step. The cutoff levels were chosen to be at the limit of detection for most analytes to identify as many positive samples as possible. Typically one ion transition was monitored from the pseudo-molecular ions in the multiple reaction monitoring mode. Of the 797 positive screening findings, 518 (65%) were confirmed by a second LC-MS-MS analysis including solid-phase extraction. Confirmed analytical findings included 22 cases positive for N-benzylpiperazine, 88 for 3,4-methylenedioxy-N-methylamphetamine and metabolites, 4 for 1-phenyl-2-butylamine, 24 for zolpidem and metabolites, 118 for zopiclone and metabolites, and 1 for zaleplon. In conclusion, LC-MS-MS was found to be a robust alternative for drugs of abuse screening, offering high sensitivity compared with immunochemical screening methodology.

  • 43.
    Nyström, Ingrid
    et al.
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Trygg, Tomas
    Woxler, Per
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Kronstrand, Robert
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Quantitation of R-(−)- and S-(+)-Amphetamine in Hair and Blood by Gas Chromatography-Mass Spectrometry: An Application to Compliance Monitoring in Adult-Attention Deficit Hyperactivity Disorder Treatment2005In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 29, no 7, p. 682-688Article in journal (Refereed)
    Abstract [en]

    Amphetamine has been used in Attention Deficit Hyperactivity Disorder (ADHD), narcolepsy, and as an appetite suppressant either as the racemate or in different proportions of its enantiomers. In Linköping, Sweden, the Department for Drug Dependence has successfully treated drug abusers also diagnosed with Adult ADHD with Metamina® [S-(+)-amphetamine]. Because of the high risk of relapse into drug abuse, a strategy involving the analysis of amphetamine enantiomers in blood and hair was investigated for the assessment of compliance as well as abstinence from street amphetamine. Four patients were included: one patient was treated with racemic amphetamine, and three with Metamina. Blood and hair samples were obtained as a part of the treatment. A basic extraction of the analytes into iso-octane was used. Hair was dissolved in sodium hydroxide before extraction. Chiral derivatization was performed by reaction with S-(−)-N-(trifluoroacetyl)prolyl chloride. Quantitation of R-(−)- and S-(+)-amphetamine was performed by gas chromatography-mass spectrometry in selected ion monitoring. Both blood and hair sample results showed good compliance for patients 1 and 2. Patient 3 and 4 showed different percentages of S-(+)-amphetamine in hair together with varying total concentrations, suggesting intake of additional racemic illicit amphetamine. During treatment, these patients also showed other signs of noncompliance, and one was temporarily withdrawn from treatment. We conclude that the method is suitable to detect therapeutic concentrations of R-(−)- and S-(+)-amphetamine in both blood and hair and that hair reveals noncompliance not shown by concentrations or enantiomer ratios in blood.

  • 44.
    Reis, Margareta
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Aamo, T.
    Ahlner, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology.
    Druid, H.
    Reference concentrations of antidepressants. A compilation of postmortem and therapeutic levels2007In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 31, no 5, p. 254-264Article in journal (Refereed)
  • 45.
    Roman, M.
    et al.
    National Board for Forensic Medicine.
    Kronstrand, Robert
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Lindstedt, D.
    National Board for Forensic Medicine.
    Josefsson, M.
    National Board for Forensic Medicine.
    Quantitation of seven low-dosage antipsychotic drugs in human postmortem blood using LC-MS-MS2008In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 32, no 2, p. 147-155Article in journal (Refereed)
    Abstract [en]

    In forensic toxicology, antipsychotic drugs are of considerable interest because of their abuse potential and their involvement in intoxications and suicides. In recent years, several new drugs dosed at low levels have entered the market and have put further demands on assays used. The aim of this work was to develop a validated liquid chromatography-tandem mass spectrometry assay for the quantitation of the low-dosage antipsychotic drugs buspirone, fluphenazine, flupenthixol, perphenazine, risperidone, ziprasidone, and zuclopenthixol in human postmortem blood. After liquid-liquid extraction using methyl t-butyl ether, compounds were separated on a Zorbax SB-CN column. Calibration curves were linear in the range 0.8-100 microg/L (r > 0.998) for all drugs. Both within- and between-day coefficients of variation were lower than 25% for all drugs at the LOQ, and extraction recoveries ranged between 58 and 112%. The possible presence of matrix effects was closely investigated. Fifty-four authentic samples were analyzed within the routine postmortem investigation, which resulted in the diagnosis of three fatal intoxications. Even though only a few intoxications were identified, the assay may present valuable information on suicidal deaths in psychotic patients where a true negative result implies noncompliance and a higher susceptibility for suicide. Without a sensitive enough method, this conclusion cannot be drawn. Therefore, we believe that antipsychotic drugs must be measured not only in toxic concentrations but also in therapeutic levels in postmortem cases

  • 46.
    Vikingsson, Svante
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Josefsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Identification of AKB-48 and 5F-AKB-48 Metabolites in Authentic Human Urine Samples Using Human Liver Microsomes and Time of Flight Mass Spectrometry2015In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 39, no 6, p. 426-435Article in journal (Refereed)
    Abstract [en]

    The occurrence of structurally related synthetic cannabinoids makes the identification of unique markers of drug intake particularly challenging. The aim of this study was to identify unique and abundant metabolites of AKB-48 and 5F-AKB-48 for toxicological screening in urine. Investigations of authentic urine samples from forensic cases in combination with human liver microsome (HLM) experiments were used for identification of metabolites. HLM incubations of AKB-48 and 5F-AKB-48 along with 35 urine samples from authentic cases were analyzed with liquid chromatography quadrupole tandem time of flight mass spectrometry. Using HLMs 41 metabolites of AKB-48 and 37 metabolites of 5F-AKB-48 were identified, principally represented by hydroxylation but also ketone formation and dealkylation. Monohydroxylated metabolites were replaced by di- and trihydroxylated metabolites within 30 min. The metabolites from the HLM incubations accounted for on average 84% (range, 67-100) and 91% (range, 71-100) of the combined area in the case samples for AKB-48 and 5F-AKB-48, respectively. While defluorinated metabolites accounted for on average 74% of the combined area after a 5F-AKB-48 intake only a few identified metabolites were shared between AKB-48 and 5F-AKB-48, illustrating the need for a systematic approach to identify unique metabolites. HLMs in combination with case samples seem suitable for this purpose.

  • 47.
    Vikingsson, Svante
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, S-58758 Linkoping, Sweden.
    Rautio, Tobias
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Wallgren, Jakob
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Åstrand, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Watanabe, Shimpei
    Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, S-58758 Linkoping, Sweden.
    Dahlén, Johan
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Wohlfarth, Ariane
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, S-58758 Linkoping, Sweden.
    Konradsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Wu, Xiongyu
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Kronstrand, Robert
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, S-58758 Linkoping, Sweden.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, S-58758 Linkoping, Sweden.
    LC-QTOF-MS Identification of Major Urinary Cyclopropylfentanyl Metabolites Using Synthesized Standards2019In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 43, no 8, p. 607-614Article in journal (Refereed)
    Abstract [en]

    Cyclopropylfentanyl is a fentanyl analog implicated in 78 deaths in Europe and over 100 deaths in the United States, but toxicological information including metabolism data about this drug is scarce. The aim of this study was to provide the exact structure of abundant and unique metabolites of cyclopropylfentanyl along with synthesis routes. In this study, metabolites were identified in 13 post-mortem urine samples using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Samples were analyzed with and without enzymatic hydrolysis, and seven potential metabolites were synthesized in-house to provide the identity of major metabolites. Cyclopropylfentanyl was detected in all samples, and the most abundant metabolite was norcyclopropylfentanyl (M1) that was detected in 12 out of 13 samples. Reference materials were synthesized (synthesis routes provided) to identify the exact structure of the major metabolites 4-hydroxyphenethyl cyclopropylfentanyl (M8), 3,4-dihydroxyphenethyl cyclopropylfentanyl (M5) and 4-hydroxy-3-methoxyphenethyl cyclopropylfentanyl (M9). These metabolites are suitable urinary markers of cyclopropylfentanyl intake as they are unique and detected in a majority of hydrolyzed urine samples. Minor metabolites included two quinone metabolites (M6 and M7), not previously reported for fentanyl analogs. Interestingly, with the exception of norcyclopropylfentanyl (M1), the metabolites appeared to be between 40% and 90% conjugated in urine. In total, 11 metabolites of cyclopropylfentanyl were identified, including most metabolites previously reported after hepatocyte incubation.

  • 48.
    Wikström, M
    et al.
    National Board of Forensic Medicine.
    Holmgren, Per
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Ahlner, Johan
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    A2 (N-benzylpiperazine) a new drug of abuse in Sweden2004In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 28, no 1, p. 67-70Article in journal (Refereed)
    Abstract [en]

    N-Benzylpiperazine was tested in the beginning of the 1970s as a possible antidepressant drug. However, in both animal and human studies, it was shown to possess amphetamine-like properties, and any further studies were stopped. In a forensic autopsy case in 1999, we found a substance so far unknown to us in the chromatogram of our method used for amphetamines. We could swiftly identify this compound as N-benzylpiperazine because of information given to us by a newly formed network comprising, among others, customs and the police. Since then, we have found N-benzylpiperazine in several cases, among them 11 cases from a number of prisons.

  • 49.
    Wikström, Maria
    et al.
    National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linköping, Sweden.
    Thelander, Gunilla
    National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linköping, Sweden.
    Dahlgren, Maria
    National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linköping, Sweden.
    Kronstrand, Robert
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linköping, Sweden.
    An Accidental Fatal Intoxication with Methoxetamine2013In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 37, no 1, p. 43-46Article in journal (Refereed)
    Abstract [en]

    This paper reports an unintentional death involving the administration of methoxetamine [2-(3-methoxyphenyl)-2-(ethylamino)-cyclohexanone] and offers some reference values from living drug abusers. Methoxetamine is a new recreational drug with a similar structure to ketamine. The deceased was a 26-year-old male with a history of drug abuse; he was found lying on the floor in his apartment. Several red-line plastic bags were found, one of which was labeled 2-(3-methoxyphenyl)-2-(ethylamino)-cyclohexanone and another labeled Haze. In four cases from living subjects with unknown doses, concentrations of methoxetamine were found from 0.13 to 0.49 g/g. In three of the cases, the blood samples also contained natural or synthetic cannabinoids. In the autopsy case, a considerably higher concentration of methoxetamine, 8.6 g/g, was found in femoral blood. In addition, tetrahydrocannabinol and the three different synthetic cannabinoids AM-694, AM-2201, and JWH-018, were present in femoral blood. The circumstances and the high femoral blood concentration of methoxetamine point toward an unintentional, acute fatal intoxication with methoxetamine, although the presence of the three synthetic cannabinoids may have contributed to the death.

1 - 49 of 49
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