| 1. |
- Andresen Bergström, Moa, 1978, et al.
(author)
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Rethinking Drug Analysis in Health Care: High-Throughput Analysis of 71 Drugs of Abuse in Oral Fluid Using Ion Mobility-High-Resolution Mass Spectrometry
- 2022
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In: Journal of Analytical Toxicology. - : Oxford University Press (OUP). - 0146-4760 .- 1945-2403. ; 46:7, s. 765-775
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Journal article (peer-reviewed)abstract
- We have identified a clinical need for a sensitive, specific, flexible, comprehensive and affordable analytical technology to efficiently detect polydrug use. In addition, the current standard practice of surveilled urine sampling is uncomfortable for the patient; hence, more patient-friendly sample collection methods are requested. To fill these needs, we have developed and validated a high-throughput liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method for the analysis of drugs of abuse (DoA) in oral fluid (OF). The method covers a panel of 71 substances including traditional DoA, prescription narcotics and new psychoactive substances (NPS), with a guaranteed limit of identification of <3 mu g/L for 87% of the analytes. Method validation showed high accuracy (>99.7%), sensitivity (>99.7%) and specificity (100%). Most analytes had a high process efficiency during the salting-out liquid-liquid extraction sample preparation and no or only a minor matrix effect during the analysis. We have implemented this method in clinical routine and present data from 18,579 OF samples collected during routine patient treatment in mainly psychiatric and addiction clinics in West Sweden between September 2020 and June 2021. Seventy-one percent of the samples were positive and a total of 41,472 DoA findings were detected. Amphetamine (27%), buprenorphine (25%), nordiazepam (18%) and alprazolam (16%) were most prevalent. New psychoactive substances were detected in 189 samples (1.0%). The occurrence of polydrug use was common; 34% of the positive samples contained three analytes or more and 12% six or more. To the best of our knowledge, this is the first method for comprehensive analysis of DoA in OF using LC-HRMS and the largest dataset published on the detection of DoA in OF. With the current complex and variable drug use pattern, this broad, cost-effective and reliable method has largely replaced immunoassay screening in urine in our laboratory.
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| 2. |
- Baginski, Steven R., et al.
(author)
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The metabolic profile of the synthetic cannabinoid receptor agonist ADB-HEXINACA using human hepatocytes, LC-QTOF-MS and synthesized reference standards
- 2023
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In: Journal of Analytical Toxicology. - : OXFORD UNIV PRESS INC. - 0146-4760 .- 1945-2403. ; 47:9, s. 826-834
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Journal article (peer-reviewed)abstract
- Synthetic cannabinoid receptor agonists (SCRAs) remain a major public health concern, with their use implicated in intoxications and drug-related deaths worldwide. Increasing our systematic understanding of SCRA metabolism supports clinical and forensic toxicology casework, facilitating the timely identification of analytical targets for toxicological screening procedures and confirmatory analysis. This is particularly important as new SCRAs continue to emerge on the illicit drug market. In this work, the metabolism of ADB-HEXINACA (ADB-HINACA, N-[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-hexyl-1H-indazole-3-carboxamide), which has increased in prevalence in the United Kingdom and other jurisdictions, was investigated using in vitro techniques. The (S)-enantiomer of ADB-HEXINACA was incubated with pooled human hepatocytes over 3 hours to identify unique and abundant metabolites using liquid chromatography-quadrupole time-of-flight mass spectrometry. In total, 16 metabolites were identified, resulting from mono-hydroxylation, di-hydroxylation, ketone formation (mono-hydroxylation then dehydrogenation), carboxylic acid formation, terminal amide hydrolysis, dihydrodiol formation, glucuronidation and combinations thereof. The majority of metabolism took place on the hexyl tail, forming ketone and mono-hydroxylated products. The major metabolite was the 5-oxo-hexyl product (M9), while the most significant mono-hydroxylation product was the 4-hydroxy-hexyl product (M8), both of which were confirmed by comparison to in-house synthesized reference standards. The 5-hydroxy-hexyl (M6) and 6-hydroxy-hexyl (M7) metabolites were not chromatographically resolved, and the 5-hydroxy-hexyl product was the second largest mono-hydroxylated metabolite. The structures of the terminal amide hydrolysis products without (M16, third largest metabolite) and with the 5-positioned ketone (M13) were also confirmed by comparison to synthesized reference standards, along with the 4-oxo-hexyl metabolite (M11). The 5-oxo-hexyl and 4-hydroxy-hexyl metabolites are suggested as biomarkers for ADB-HEXINACA consumption.
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| 15. |
- Cherma Yeste, Maria Dolores, et al.
(author)
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Use of Lisdexamfetamine or Amphetamine? Interpretation of Chiral Amphetamine Analyses
- 2022
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In: Journal of Analytical Toxicology. - : OXFORD UNIV PRESS INC. - 0146-4760 .- 1945-2403. ; 46:1, s. 10-16
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Journal article (peer-reviewed)abstract
- Amphetamine is frequently detected in forensic toxicological cases. Differentiating between the two isomers of amphetamine (d-amphetamine and l-amphetamine) and determining their relative proportion are fundamental to correctly interpret the results of toxicological analyses. The aim of this study was to examine the profile of amphetamine as well as storage stability of the isomers in authentic samples from patients chronically treated with lisdexamfetamine (LDX), the most prescribed medical amphetamine product in Sweden. Blood and urine samples were collected from 18 patients. The samples were analyzed with an achiral (racemate) method for quantification of amphetamine and with a chiral method to determine the proportion of each isomer of amphetamine. The median daily dose of LDX was 40 mg (range, 20-70 mg). The median amphetamine concentration was 0.06 mu g/g (range, 0.02-0.15 mu g/g) in blood and 6 mu g/mL (range, 1-22 mu g/mL) in urine. Only d-amphetamine was found in the blood and urine samples from the included patients. Furthermore, no formation of l-amphetamine occurred during the storage for 3 months at 4 degrees C, 9 months at -20 degrees C and three freeze-thaw cycles. The results from this study may be helpful in the interpretation of whether the source of identified amphetamine in biological samples is from LDX drug intake or not.
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| 16. |
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| 17. |
- DeFreitas, Laura, et al.
(author)
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Fast and Sensitive Method for the Determination of 17 Designer Benzodiazepines in Hair by Liquid Chromatography-Tandem Mass Spectrometry
- 2022
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In: Journal of Analytical Toxicology. - : OXFORD UNIV PRESS INC. - 0146-4760 .- 1945-2403. ; 46:8, s. 852-859
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Journal article (peer-reviewed)abstract
- In recent years, identification and analysis of designer benzodiazepines have become a challenge in forensic toxicology. These substances are analogs of the classic benzodiazepines, but their pharmacology is not well known, and many of them have been associated with overdoses and deaths. As a result, there has been a surge in efforts to develop analytical methods to determine these compounds in different biological samples. Our aim was to develop and validate a fast, sensitive and specific method for determining 17 designer benzodiazepines (adinazolam, clobazam, clonazolam, delorazepam, deschloroetizolam, diclazepam, etizolam, flualprazolam, flubromazepam, flubromazolam, flunitrazolam, N-desmethylclobazam, nifoxipam, nitrazolam, meclonazepam, pyrazolam and zolazepam) in hair by liquid chromatography-tandem mass spectrometry (LC-MS-MS). Hair samples were decontaminated and pulverized, and a 20 mg aliquot was incubated in methanol in an ultrasound bath (1 h, 25 degrees C). The supernatant was evaporated and reconstituted in 200 mu L of mobile phase, and the extracts were filtered (nano-filter vials) before injection into LC-MS-MS. All analytes were eluted from the chromatographic column in 8 min, and two multiple-reaction monitoring (MRM) transitions were used to identify each compound. The limits of quantification were 5 or 25 pg/mg depending on the analyte, and the calibration functions were linear to 200 pg/mg. Imprecision was <19.2% (n = 15), and bias was from -13.7 to 18.3% (n = 15). All the analytes yielded high extraction efficiencies >70% and displayed ion suppression between -62.8% and -23.9% (n = 10). The method was applied to 19 authentic cases. Five samples were positive for flualprazolam ( 200 pg/mg) and/or etizolam (47.4-88.5 pg/mg). In conclusion, the present validated method has proven to be fast, sensitive, specific and capable of determining 17 designer benzodiazepines in hair using LC-MS-MS.
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| 18. |
- Elenstal, Emily, et al.
(author)
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Intralipid as a matrix additive for evaluating hyperlipidemic postmortem blood
- 2023
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In: Journal of Analytical Toxicology. - : OXFORD UNIV PRESS INC. - 0146-4760 .- 1945-2403. ; 47:6, s. 529-534
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Journal article (peer-reviewed)abstract
- Postmortem whole blood samples can differ greatly in quality where hyperlipemia is a frequent variable that can influence the results of analytical methods. The aim of this study was to investigate the influence of lipemia on postmortem analysis as well as demonstrate the usage of Intralipid in comparison to pooled postmortem lipids as matrix additives for meaningful evaluation and validation of hyperlipidemic postmortem samples. Hyperlipidemic blood samples were simulated by adding different concentrations of Intralipid or pooled authentic postmortem lipids to bovine whole blood. The hyperlipidemic blood samples were spiked with 14 benzodiazepines and five sedative and antianxiety drugs (alprazolam, clonazepam, 7-aminoclonazepam, diazepam, flunitrazepam, 7-aminoflunitrazepam, hydroxyzine, lorazepam, midazolam, nitrazepam, 7-aminonitrazepam, nordazepam, oxazepam, propiomazine, dihydropropiomazine, temazepam, triazolam, zolpidem and zopiclone). Samples were prepared with liquid-Liquid extraction followed by ultra-high performance liquid chromatography-mass spectrometry. The effects of lipemia on the recovery of analytes and internal standards (ISs) were evaluated to determine the effect of, and any differences between, the two additives. Lipemia was found to cause major interference when quantifying the analytes. For most analytes, the ISs could compensate for analyte losses. However, the most hydrophilic analytes (7-amino metabolites), together with the most lipophilic analytes (propiomazine and dihydropropiomazine), were greatly affected by lipemia (<50% recovery), and the IS could not compensate for analyte losses. In general, lower analyte recoveries were observed for samples with Intralipid as a lipemic additive in comparison to those containing pooled postmortem lipids. Both Intralipid and pooled postmortem lipids showed marked effects on the analytical results. Intralipid gave a good indication of the effects of lipemia and could be a useful tool for making a meaningful evaluation of hyperlipidemic postmortem samples during the method development and validation.
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| 19. |
- Faniband, Moosa, et al.
(author)
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Biomarkers of Exposure to Pyrimethanil After Controlled Human Experiments
- 2019
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In: Journal of Analytical Toxicology. - : Oxford University Press (OUP). - 1945-2403 .- 0146-4760. ; 43:4, s. 277-283
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Journal article (peer-reviewed)abstract
- Pyrimethanil (PYM) is a fungicide used pre- and post-harvest on many crops. It has a low acute toxicity but is of toxicological concern because of its antiandrogenic properties. The aim of the current work was to investigate some metabolism and estimate elimination kinetics of PYM in humans after experimental oral and dermal exposure. A liquid chromatography triple quadrupole mass spectrometry (LC-MS-MS) method was developed and validated for the analysis of PYM and its metabolite 4-hydroxypyrimethanil (OH-PYM) in human urine. The method was applied to analyze urine obtained from two volunteers experimentally exposed to PYM. The elimination of OH-PYM seemed to follow first-order kinetics and a two-phase excretion. After the oral exposure, the elimination half-life of OH-PYM in the rapid phase was 5 and 3 h for the female and male volunteer, respectively. In the slower phase, it was 15 h in both volunteers. After the dermal exposure, the half-life in the rapid phase was 8 h in both volunteers. In the slower phase, it was 30 and 20 h, respectively. About 80% of the oral dose was recovered as urinary OH-PYM in both volunteers. The dermal dose recovered as urinary OH-PYM was 9.4% and 19%, in the female and male volunteer, respectively. OH-PYM was mainly found as a conjugate of sulfonate and glucuronic acid. No free PYM was found. The analytical method showed good within-run, between-run and between-batch precision with a coefficient of variation between 6% and 12%. A limit of detection of 0.1 ng/mL and a limit of quantification of 0.4 ng/mL were achieved for both the analytes. The method was applied to biomonitor PYM exposure in populations in Sweden. OH-PYM was detected in nearly 50% and 96% of samples from the environmentally and occupationally exposed populations, respectively.
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| 20. |
- Faniband, Moosa, et al.
(author)
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LC-MS-MS Analysis of Urinary Biomarkers of Imazalil Following Experimental Exposures.
- 2015
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In: Journal of Analytical Toxicology. - : Oxford University Press (OUP). - 1945-2403 .- 0146-4760. ; 39:9, s. 691-697
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Journal article (peer-reviewed)abstract
- Imazalil (IMZ) is a fungicide used in the cultivation of vegetables, such as cucumbers, in green houses or post-harvest on fruit to avoid spoilage due to fungal growth. Agricultural workers can be occupationally exposed to IMZ and the general public indirectly by the diet. The purpose of this study was to develop and validate an LC-MS-MS method for the analysis of IMZ in human urine. The method used electrospray ionization and selected reaction monitoring in the positive mode. Excellent linearity was observed in the range 0.5-100 ng/mL. The limit of detection of the method was 0.2 ng/mL, and the limit of quantitation 0.8 ng/mL. The method showed good within-run, between-run and between-batch precision, with a coefficient of variation <15%. The method was applied to analyze urine samples obtained from two human volunteers following experimental oral and dermal exposure. The excretion of IMZ seemed to follow a two-compartment model and first-order kinetics. In the oral exposure, the elimination half-life of IMZ in the rapid excretion phase was 2.6 and 1.9 h for the female and the male volunteer, respectively. In the slower excretion phase, it was 7.6 and 13 h, respectively. In the dermal exposure, the excretion seemed to follow a single-compartment model and first-order kinetics. The elimination half-life was 10 and 6.6 h for the female and the male volunteer, respectively. Although the study is limited to two volunteers, some information on basic toxicokinetics and metabolism of IMZ in humans is presented.
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| 21. |
- Forsman, M., et al.
(author)
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Urinary detection times and excretion patterns of flunitrazepam and its metabolites after a single oral dose
- 2009
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In: Journal of Analytical Toxicology. - 0146-4760 .- 1945-2403. ; 33:8, s. 491-501
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Journal article (peer-reviewed)abstract
- 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.
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| 22. |
- Guerrieri, Davide, et al.
(author)
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Postmortem and Toxicological Findings in a Series of Furanylfentanyl-Related Deaths
- 2017
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In: Journal of Analytical Toxicology. - : OXFORD UNIV PRESS INC. - 0146-4760 .- 1945-2403. ; 41:3, s. 242-249
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Journal article (peer-reviewed)abstract
- 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.
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| 23. |
- Guerrieri, Davide, et al.
(author)
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Validation and Cross-Reactivity Data for Fentanyl Analogs With the Immunalysis Fentanyl ELISA
- 2019
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In: Journal of Analytical Toxicology. - : OXFORD UNIV PRESS INC. - 0146-4760 .- 1945-2403. ; 43:1, s. 18-24
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Journal article (peer-reviewed)abstract
- 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.
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| 24. |
- Gundersen, Per Ole M., et al.
(author)
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Metabolite Profiling of Ortho-, Meta- and Para-Fluorofentanyl by Hepatocytes and High-Resolution Mass Spectrometry
- 2020
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In: Journal of Analytical Toxicology. - : Oxford University Press. - 0146-4760 .- 1945-2403. ; 44:2, s. 140-148
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Journal article (peer-reviewed)abstract
- New psychoactive substances are emerging on the illegal drug market. Synthetic opioids including fentanyl analogues are of special concern due to their high potency. This indicates the possibility of low drug concentrations in vivo and calls for sensitive analytical methods and identification of the most appropriate analytical targets. In this study the in vitro metabolism of ortho-, meta- and para-fluorofentanyl, three fluorinated derivatives of fentanyl, has been investigated using human hepatocytes and compared to the results from an authentic human urine sample. Based on knowledge on the metabolism of similar fentanyl analogues N-dealkylation and hydroxylation was hypothesized to be the most central pathways. The three fluorofentanyl isomers were incubated with pooled human hepatocytes at 1, 3 and 5 h. Liquid chromatography quadrupole time of flight mass spectrometry operating in data-dependent mode was used to analyse the hepatocyte samples, as well as the hydrolysed and non-hydrolysed authentic urine sample. Data were analysed by a targeted approach with a database of potential metabolites. The major metabolite formed in vitro was the N-dealkylation product norfluorofentanyl. In addition various hydroxylated metabolites, a N-oxide, dihydrodiol metabolites and a hydroxymethoxy metabolite were found. In total, 14 different metabolites were identified for each fluorofentanyl isomer. In the authentic urine sample, three metabolites were detected in addition to the ortho-fluorofentanyl parent compound, with hydroxymethoxy metabolite having the highest abundance followed by norfluorofentanyl and a metabolite hydroxylated on the ethylphenyl ring. This in vitro study showed that the metabolic pattern for ortho-, meta-, and para-fluorofentanyl was close to those previously reported for other fentanyl analogues. We suggest that the hydroxymethoxy metabolite and the metabolite hydroxylated on the ethylphenyl ring should be the metabolites primarily investigated in further studies to determine the most appropriate marker for intake of fluorofentanyl derivatives in urine drug screening for human subjects.
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| 25. |
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| 26. |
- Holmgren, Per, et al.
(author)
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Enantioselective analysis of citalopram and its metabolites in postmortem blood and genotyping for CYD2D6 and CYP2C19
- 2004
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In: Journal of Analytical Toxicology. - : Oxford University Press (OUP). - 0146-4760 .- 1945-2403. ; 28:2, s. 94-104
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Journal article (peer-reviewed)abstract
- 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.
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| 27. |
- Jakobsson, Gerd, et al.
(author)
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Heroin-Related Compounds and Metabolic Ratios in Postmortem Samples Using LC-MS-MS
- 2021
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In: Journal of Analytical Toxicology. - : Oxford University Press. - 0146-4760 .- 1945-2403. ; 45:3, s. 215-225
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Journal article (peer-reviewed)abstract
- Analysis of postmortem samples with the presence of morphine can sometimes be challenging to interpret. Tolerance complicates interpretation of intoxications and causes of death due to overlap in therapeutic and fatal concentrations. Determination of metabolites and metabolic ratios can potentially differentiate between abstinence, continuous administration, and perhaps time of administration. The purpose of this study was to (a) develop and validate a method for quantitation of morphine-3 beta-D-glucuronide, morphine-6 beta-D-glucuronide, normorphine, codeine-6 beta-D-glucuronide, norcodeine, codeine, 6-acetylmorphine, and ethylmorphine in urine using liquid chromatography-tandem mass spectrometry; (b) apply the method to opiate related deaths; (c) compare metabolic ratios in urine in different causes of death (CoD) and after different drug intakes and (d) compare heroin intoxications in rapid and delayed deaths. Validation parameters such as precision, bias, matrix effects, stability, process efficiency, and dilution integrity were assessed and deemed acceptable. Lower limits of quantitation ranged from 0.01-0.2 mu g/mL for all analytes. Autopsy cases (n=135) with paired blood and urine samples were analyzed. Cases were divided into three groups based on CoD; opiate intoxication, intoxication with other drugs than opiates, and other CoD. The cases were classified by intake: codeine (n=42), heroin (n=36), morphine (n=49), and ethylmorphine (n=3). Five cases were classified as mixed intakes and excluded. Heroin intoxications (n=35) were divided into rapid (n=15) or delayed (n=20) deaths. Parent drug groups were compared using metabolic ratio morphine-3 beta-D-glucuronide/morphine and significant differences were observed between codeine vs morphine (p=0.005) and codeine vs heroin (p <= 0.0001). Urine and blood concentrations, and metabolic ratios in rapid and delayed heroin intoxications were compared and determined a significant difference for morphine (p=0.001), codeine (p=0.009), 6-acetylmorphine (p=0.02) in urine, and morphine (p=0.02) in blood, but there was no significant difference (p=0.9) between metabolic ratios. Morphine-3 beta-D-glucuronide results suggested a period of abstinence prior to death in 25% of the heroin intoxications.
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| 28. |
- Jakobsson, Gerd, et al.
(author)
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Oxycodone Concentrations and Metabolic Ratios in Femoral Blood from Fatal Intoxications and Other Causes of Death using LC-MS-MS
- 2021
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In: Journal of Analytical Toxicology. - : OXFORD UNIV PRESS INC. - 0146-4760 .- 1945-2403. ; 45:2, s. 124-133
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Journal article (peer-reviewed)abstract
- Oxycodone (OC) is an opioid with strong analgesic effects widely used to treat acute and chronic pain. Interpretation of OC concentrations in postmortem cases is complicated due to tolerance and overlapping concentrations for fatal and non-fatal levels. In this study, our aim was to develop and validate a method for OC and its three metabolites: noroxycodone (NOC), oxymorphone (OM) and noroxymorphone (NOM) in postmortem femoral blood. Our goal was to define reference concentrations for intoxications and non-intoxications and investigate metabolic ratios in different causes of death. A rapid LC-MS-MS method using protein-precipitated postmortem blood was developed. Lower limit of quantitation was 0.005 mu g/g blood for all analytes; upper limit of quantitation was 1.0 mu g/g for OC and NOC and 0.25 mu g/g for OM and NOM. The method displayed high precision (3.3-7.7%) and low bias (-0.3 to 12%). In total, 192 cases were analyzed and concentrations ranged from 0.005 to 13 mu g/g for OC, 0.005 to 2.0 mu g/g for NOC, 0.005 to 0.24 mu g/g for OM, and 0.005 to 0.075 mu g/g for NOM. We found a significant difference in OC concentration between the cases where OC contributed and those where it did not. In spite of that, we do not recommend the use of a specific blood concentration to distinguish fatal intoxications. Instead, the percentiles from our data set suggest that concentrations >0.2 mu g/g are likely to have contributed to toxicity, but that concentrations as high as 0.3 might be tolerated without toxic effects. In addition, we also found that a low NOC/OC ratio could point toward an acute fatal intoxication. In conclusion, the OC concentration alone may not be sufficient to diagnose a fatal intoxication.
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| 29. |
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| 30. |
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| 31. |
- Jones, A Wayne
(author)
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Bibliometric evaluation of Journal of Analytical Toxicology as a scholarly publication according to the Web-of-Science citation database
- 2023
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In: Journal of Analytical Toxicology. - : OXFORD UNIV PRESS INC. - 0146-4760 .- 1945-2403.
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Journal article (peer-reviewed)abstract
- Soon approaching its 50th anniversary, Journal of Analytical Toxicology (JAT) is an international scholarly publication specializing in analytical and forensic aspects of toxicology. Science Citation Index (SCI) and Journal Citation Reports (JCR), both of which are part of the Web-of-Science (WOS) database, were used to make a bibliometric evaluation of JAT articles. Between 1977 (volume 1) and 2023 (volume 47), a total of n = 4,785 items were published in JAT; the top-ten most highly cited articles and the most prolific authors were identified. Changes in the journal impact factor (JIF) were studied between 1997 and 2022, and this metric varied from a low of 1.24 (2006) to a high of 3.36 (2020).The most recent JIF (2022) dropped to 2.5 and the corresponding 5 year JIF was 2.6. JATs most highly cited article (590 cites) was a working group (SWGTOX) report dealing with standard practices for the validation of analytical methods in forensic toxicology laboratories. JAT published 62 articles each of which were cited over 100 times and the H-index for JAT was 89. The most prolific author of JAT articles was credited with 119 items, the first in 1980 (volume 4) and the latest in 2023 (volume 47). JAT articles were cited 4,537 times in 2022 by all journals in the JCR database, although 520 of these were self-citations (11.5%). Bibliometric methods are increasingly used to evaluate the published work of individual scientists, university departments, entire universities and whole countries. Highly cited articles are considered more influential and authoritative compared with papers that are seldom or never cited.
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| 32. |
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| 33. |
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| 34. |
- Jones, A Wayne, et al.
(author)
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Concentration Ratios of Methamphetamine to Amphetamine in Blood Can Help to Distinguish Use of Methamphetamine from Various Mixtures of the Two Stimulants
- 2012
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In: Journal of Analytical Toxicology. - : Oxford University Press (OUP): Policy F. - 0146-4760 .- 1945-2403. ; 36:9, s. 634-637
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Journal article (peer-reviewed)abstract
- 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.
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| 35. |
- Jones, A Wayne, et al.
(author)
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Concentration-Time Profiles of Gamma-Hydroxybutyrate in Blood After Recreational Doses are Best Described by Zero-Order Rather Than First-Order Kinetics
- 2009
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In: Journal of Analytical Toxicology. - 0146-4760 .- 1945-2403. ; 33:6, s. 332-335
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Journal article (peer-reviewed)abstract
- 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.
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| 36. |
- Jones, A Wayne, et al.
(author)
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Concentrations of Cocaine and Benzoylecgonine in Femoral Blood from Cocaine-Related Deaths Compared with Venous Blood from Impaired Drivers
- 2014
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In: Journal of Analytical Toxicology. - : Oxford University Press (OUP): Policy F. - 0146-4760 .- 1945-2403. ; 38:1, s. 46-51
-
Journal article (peer-reviewed)abstract
- 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.
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| 37. |
- Jones, A Wayne, 1945-, et al.
(author)
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Driving under the influence of opiates : Concentration relationships between morphine, codeine, 6-acetyl morphine, and ethyl morphine in blood
- 2008
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In: Journal of Analytical Toxicology. - 0146-4760 .- 1945-2403. ; 32:4, s. 265-272
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Journal article (peer-reviewed)abstract
- 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.
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| 38. |
- Jones, Alan Wayne
(author)
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Dubowski's stages of alcohol influence and clinical signs and symptoms of drunkenness in relation to a person's blood-alcohol concentration-Historical background
- 2024
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In: Journal of Analytical Toxicology. - : OXFORD UNIV PRESS INC. - 0146-4760 .- 1945-2403.
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Research review (peer-reviewed)abstract
- This article traces the origin of various charts and tables delineating the stages of alcohol influence in relation to the clinical signs and symptoms of drunkenness and a person's blood-alcohol concentration (BAC). In forensic science and legal medicine, the most widely used such table was created by Professor Kurt M. Dubowski (University of Oklahoma). The first version of the Dubowski alcohol table was published in 1957, and minor modifications appeared in various articles and book chapters until the final version was published in 2012. Seven stages of alcohol influence were identified including subclinical (sobriety), euphoria, excitement, confusion, stupor, alcoholic coma and death. The BAC causing death was initially reported as 0.45+ g%, although the latest version cited a mean and median BAC of 0.36 g% with a 90% range from 0.21 g% to 0.50 g%. An important feature of the Dubowski alcohol table was the overlapping ranges of BAC for each of the stages of alcohol influence. This was done to reflect variations in the physiological effects of ethanol on the nervous system between different individuals. Information gleaned from the Dubowski table is not intended to apply to any specific individual but more generally for a population of social drinkers, not regular heavy drinkers or alcoholics. Under real-world conditions, much will depend on a person's age, race, gender, pattern of drinking, habituation to alcohol and the development of central nervous tolerance. The impairment effects of ethanol also depend to some extent on whether observations are made on the rising or declining phase of the blood-alcohol curve (Mellanby effect). There will always be some individuals who do not exhibit the expected behavioral impairment effects of ethanol, such as regular heavy drinkers and those suffering from an alcohol use disorder.
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| 39. |
- Jones, A Wayne, 1945-
(author)
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Elimination half-life of acetone in humans : Case reports and review of the literature
- 2000
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In: Journal of Analytical Toxicology. - 0146-4760 .- 1945-2403. ; 24:1
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Journal article (peer-reviewed)abstract
- 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.
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| 40. |
- Jones, A Wayne, 1945-
(author)
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Forensic Drug Profile: Cocaethylene
- 2019
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In: Journal of Analytical Toxicology. - : OXFORD UNIV PRESS INC. - 0146-4760 .- 1945-2403. ; 43:3, s. 155-160
-
Research review (peer-reviewed)abstract
- 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.
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| 41. |
- Jones, A Wayne, 1945-, et al.
(author)
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Gamma-hydroxybutyrate concentrations in the blood of impaired drivers, users of illicit drugs, and medical examiner cases
- 2007
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In: Journal of Analytical Toxicology. - 0146-4760 .- 1945-2403. ; 31:9, s. 566-572
-
Journal article (peer-reviewed)abstract
- 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.
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| 42. |
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| 43. |
- Jones, A Wayne, 1945-
(author)
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Impact of JAT publications 1981-2003 : The most prolific authors and the most highly cited articles
- 2004
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In: Journal of Analytical Toxicology. - 0146-4760 .- 1945-2403. ; 28:7, s. 541-545
-
Journal article (peer-reviewed)abstract
- 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.
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- Jones, A Wayne, 1945-
(author)
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Letter to the editor : Body mass index and blood-alcohol calculations
- 2007
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In: Journal of Analytical Toxicology. - : Oxford University Press. - 0146-4760 .- 1945-2403. ; 31:3, s. 177-178
-
Journal article (other academic/artistic)abstract
- 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.
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| 48. |
- Jones, A Wayne, 1945-
(author)
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Reference limits for urine/blood ratios of ethanol in two successive voids from drinking drivers
- 2002
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In: Journal of Analytical Toxicology. - 0146-4760 .- 1945-2403. ; 26:6, s. 333-339
-
Journal article (peer-reviewed)abstract
- 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.
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| 49. |
- Jones, A Wayne, et al.
(author)
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Relationship Between Postmortem Urine and Blood Concentrations of GHB Furnishes Useful Information to Help Interpret Drug Intoxication Deaths
- 2018
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In: Journal of Analytical Toxicology. - : OXFORD UNIV PRESS INC. - 0146-4760 .- 1945-2403. ; 42:9, s. 587-591
-
Journal article (peer-reviewed)abstract
- 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.
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| 50. |
- Jones, A Wayne, 1945-
(author)
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Review of Caffeine-Related Fatalities along with Postmortem Blood Concentrations in 51 Poisoning Deaths
- 2017
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In: Journal of Analytical Toxicology. - : OXFORD UNIV PRESS INC. - 0146-4760 .- 1945-2403. ; 41:3, s. 167-172
-
Research review (peer-reviewed)abstract
- 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.
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