nach oben

Forensic Toxicology

Erschienen in:

10.05.2021 | Minireview

Blood concentrations of new psychoactive substances belonging to benzodiazepine class

verfasst von: Karolina Nowak, Piotr Adamowicz

Erschienen in: Forensic Toxicology | Ausgabe 2/2021

Einloggen, um Zugang zu erhalten

Abstract

Purpose

There has been a global increase in the number and availability of new psychoactive substances (NPS) belonging to the benzodiazepine class. New benzodiazepines are much more dangerous to health and life than pharmaceutical benzodiazepines. These substances have been associated with many deaths. Interpreting own results usually requires a comparison to previously published cases; therefore, a referenced compilation of previously published concentration data would be useful.

Methods

The data collection was based on a search of PubMed, Scopus, and Google search engine. All available data from articles and reports that measured new benzodiazepine concentrations in plasma, serum, or whole blood were included in the data analysis.

Results

The presented tables list the observed concentrations in fatal and nonfatal cases involving 13 NPS belonging to the benzodiazepine class.

Conclusions

The interpretation of the concentrations of the NPS belonging to the benzodiazepine class is difficult. Concomitant use of benzodiazepines and other drugs as well as other factors often contribute to toxic effects or deaths in real cases. This report enables quick access to the source articles quantifying new benzodiazepines.

European Monitoring Centre for Drugs and Drug Addiction (2020) New psychoactive substances: global markets, global threats and the COVID-19 pandemic. An update from the EU Early Warning System. Publications office of the European Union, Luxembourg. https://doi.org/10.2810/921262CrossRef

European Monitoring Centre for Drugs and Drug Addiction (2020) European drug report 2020: trends and developments. Publications office of the European Union, Luxembourg. https://doi.org/10.2810/420678CrossRef

United Nations Office on Drugs and Crime (2017) Global smart update volume 18. Non-medical use of benzodiazepines: a growing threat to public health? Vienna International Centre, Vienna. https://www.unodc.org/documents/scientific/Global_SMART_Update_2017_Vol_18.pdf. Accessed 15 Mar 2021

Garcia L, Tiscione NB, Yeatman DT, Richards-Waugh L (2020) Novel and nonroutine benzodiazepines and suvorexant by LC-MS-MS. J Anal Toxicol. https://doi.org/10.1093/jat/bkaa109 [ahead of print]CrossRef

Heide G, Høiseth G, Middelkoop G, Øiestad ÅML (2020) Blood concentrations of designer benzodiazepines: relations to impairment and findings in forensic cases. J Anal Toxicol 44:905–914. https://doi.org/10.1093/jat/bkaa043CrossRefPubMedPubMedCentral

Høiseth G, Tuv SS, Karinen R (2016) Blood concentrations of new designer benzodiazepines in forensic cases. Forensic Sci Int 268:35–38. https://doi.org/10.1016/j.forsciint.2016.09.006CrossRefPubMed

Murphy L, Melamed J, Gerona R, Hendrickson RG (2019) Clonazolam: a novel liquid benzodiazepine. Toxicol Commun 3:75–78. https://doi.org/10.1080/24734306.2019.1661568(open access article)CrossRef

Sommerfeld-Klatta K, Łukasik-Głębocka M, Teżyk A, Panieński P, Żaba C, Zielińska-Psuja B (2020) Clonazolam a new designer benzodiazepine intoxication confirmed by blood concentration. Forensic Sci Int 310:110237. https://doi.org/10.1016/j.forsciint.2020.110237CrossRefPubMed

Židková M, Horsley R, Hloch O, Hložek T (2019) Near-fatal intoxication with the “new” synthetic opioid U-47700: the first reported case in the Czech Republic. J Forensic Sci 64:647–650. https://doi.org/10.1111/1556-4029.13903CrossRefPubMed

10.

Gerace E, Bovetto E, Di Corcia D, Vincenti M, Salomone A (2017) A case of nonfatal intoxication associated with the recreational use of diphenidine. J Forensic Sci 62:1107–1111. https://doi.org/10.1111/1556-4029.13355CrossRefPubMed

11.

Arens AM, van Wijk XMR, Vo KT, Lynch KL, Wu AHB, Smollin CG (2016) Adverse effects from counterfeit alprazolam tablets. JAMA Intern Med 176:1554–1555. https://doi.org/10.1001/jamainternmed.2016.4306CrossRefPubMed

12.

García MAF, de Labry O, Lima A, Ferrer Lopez I, Bermúdez-Tamayo C (2018) Analysis of changes in trends in the consumption rates of benzodiazepines and benzodiazepine-related drugs. J Pharm Policy Pract 11:1. https://doi.org/10.1186/s40545-017-0128-4(open access article)CrossRefPubMedPubMedCentral

13.

Kato Z, Nakamura M, Funato M, Kuwabara H, Kondo N (2007) Accidental etizolam ingestion in a child. Pediatr Emerg Care 23:472–473. https://doi.org/10.1097/01.pec.0000280511.13537.bdCrossRefPubMed

14.

Rohrig TP, Osawa KA, Baird TR, Youso KB (2021) Driving impairment cases involving etizolam and flubromazolam. J Anal Toxicol 45:93–98. https://doi.org/10.1093/jat/bkaa050CrossRefPubMed

15.

Blumenberg A, Hughes A, Reckers A, Ellison R, Gerona R (2020) Flualprazolam: report of an outbreak of a new psychoactive substance in adolescents. Pediatrics 146:e20192953. https://doi.org/10.1542/peds.2019-2953(open access article)CrossRefPubMed

16.

Papsun DM, Krotulski AJ, Homan J, Temporal KDH, Logan BK (2020) Flualprazolam blood concentrations in 197 forensic investigation cases. J Anal Toxicol 45:226–232. https://doi.org/10.1093/jat/bkaa070CrossRef

17.

Valli A, Lonati D, Locatelli CA, Buscaglia E, Di Tuccio M, Papa P (2017) Analytically diagnosed intoxication by 2-methoxphenidine and flubromazepam mimicking an ischemic cerebral disease. Clin Toxicol 55:611–612. https://doi.org/10.1080/15563650.2017.1286016CrossRef

18.

Łukasik-Głębocka M, Sommerfeld K, Teżyk A, Zielińska-Psuja B, Panieński P, Żaba C (2016) Flubromazolam—a new life-threatening designer benzodiazepine. Clin Toxicol 54:66–68. https://doi.org/10.3109/15563650.2015.1112907CrossRef

19.

Bailey K, Richards-Waugh L, Clay D, Gebhardt M, Mahmoud H, Kraner JC (2010) Fatality involving the ingestion of phenazepam and poppy seed tea. J Anal Toxicol 34:527–532. https://doi.org/10.1093/jat/34.8.527(open access article)CrossRefPubMed

20.

Dargan PI, Davies S, Puchnarewicz M, Johnston A, Wood DM (2013) First reported case in the UK of acute prolonged neuropsychiatric toxicity associated with analytically confirmed recreational use of phenazepam. Eur J Clin Pharmacol 69:361–363. https://doi.org/10.1007/s00228-012-1361-zCrossRefPubMed

21.

Kerrigan S, Mellon MB, Hinners P (2013) Detection of phenazepam in impaired driving. J Anal Toxicol 37:605–610. https://doi.org/10.1093/jat/bkt075(open access article)CrossRefPubMed

22.

Kriikku P, Wilhelm L, Rintatalo J, Hurme J, Kramer J, Ojanperä I (2012) Phenazepam abuse in Finland: findings from apprehended drivers, post-mortem cases and police confiscations. Forensic Sci Int 220:111–117. https://doi.org/10.1016/j.forsciint.2012.02.006CrossRefPubMed

23.

Mykkänen S, Gunnar T, Ariniem K, Lillsunde P, Krasnova R (2005) Quantitation of phenazepam in blood by GC-MS in positive drug-driving cases in Finland. In: 2004 SOFT-TIAFT Meeting Abstracts, No. A80. J Anal Toxicol 29:443–444. https://doi.org/10.1093/jat/29.5.413 CrossRef

24.

Pinorini-Godly MT, Spokert F, Schläpfer M, Rusconi M, Conti A (2010) Intoxication with butylone and phenazepam among young cocaine users. In: Abstracts of TIAFT-GTFCh joint meeting, P-83. Toxichem Krimtech 77:226–227

25.

Stephenson JB, Golz DE, Brasher MJ (2013) Phenazepam and its effects on driving. J Anal Toxicol 37:25–29. https://doi.org/10.1093/jat/bks080 (open access article)CrossRefPubMed

26.

Vo KT, Van Wijk XMR, Wu AHB, Lynch KL, Ho RY (2017) Synthetic agents off the darknet: a case of U-47700 and phenazepam abuse. Clin Toxicol 55:71–72. https://doi.org/10.1080/15563650.2016.1240806CrossRef

27.

Wilhelm L, Jenckel S, Kriikku P, Rintatalo J, Hurme J, Kramer J (2011) Phenazepam—a new drug of abuse in Finland – findings from apprehended drivers. Toxichem Krimtech 78:302–305

28.

Ishigami A, Kubo S, Hara K, Waters B, Tokunaga I, Nishimura A (2019) Fatal accidental asphyxia in the reverse jack-knife position on a chair with wheels. Leg Med 36:81–84. https://doi.org/10.1016/j.legalmed.2018.11.001CrossRef

29.

Nowak K, Szpot P, Zawadzki M (2021) Fatal intoxication with U-47700 in combination with other NPS (N-ethylhexedrone, adinazolam, 4-CIC, 4-CMC) confirmed by identification and quantification in autopsy specimens and evidences. Forensic Toxicol. https://doi.org/10.1007/s11419-020-00568-1 [ahead of print] (open access article)CrossRef

30.

Mei V, Concheiro M, Pradi J, Cooper G (2019) Validation of an LC-MS/MS method for the quantification of 13 designer benzodiazepines in blood. J Anal Toxicol 43:688–695. https://doi.org/10.1093/jat/bkz063CrossRefPubMed

31.

Gerace E, Salomone A, Di Corcia D, Mazzucco P, Vincenti M (2015) Postmortem redistribution of triazolam, alprazolam, delorazepam (chlordesmethyldiazepam) and zolpidem in a suicide case. Toxicol Anal Clin 27:233–238. https://doi.org/10.1016/j.toxac.2015.10.001CrossRef

32.

Gummin DD, Mowry JB, Spyker DA, Brookd DE, Osterthaler KM, Banner W (2018) 2017 Annual report of the American Association of Poison Control Centers’ national poison data system (NPDS): 35th annual report. Clin Toxicol 56:1213–1415. https://doi.org/10.1080/15563650.2018.1533727CrossRef

33.

Lehmann S, Sczyslo A, Froch-Cortis J, Rothschild MA, Thevis M, Andersen-Streichert H, Mercer-Chalmers-Bender K (2019) Organ distribution of diclazepam, pyrazolam and 3-fluorophenmetrazine. Forensic Sci Int 303:109959. https://doi.org/10.1016/j.forsciint.2019.109959CrossRefPubMed

34.

O’Connor L (2020) Detection of designer benzodiazepines in Scottish sub-populations. PhD Thesis. University of Glasgow, Glasgow, United Kingdom. http://theses.gla.ac.uk/81840/. Accessed 15 Mar 2021

35.

El Balkhi S, Chaslot M, Picard N, Dulaurent S, Delage M, Mathieu O, Saint-Marcoux F (2017) Characterization and identification of eight designer benzodiazepine metabolites by incubation with human liver microsomes and analysis by a triple quadrupole mass spectrometer. Int J Legal Med 131:979–988. https://doi.org/10.1007/s00414-017-1541-6CrossRefPubMed

36.

Hikin LJ, Smith PR, Maskell PD, Kurimbokus H, Ashong E, Couchman L, Morley SR (2020) Femoral blood concentrations of the designer benzodiazepine etizolam in post-mortem cases. Med Sci Law. https://doi.org/10.1177/0025802420973814CrossRefPubMed

37.

Partridge E, Trobbiani S, Stockham P, Charlwood C, Kostakis C (2018) A case study involving U-47700, diclazepam and flubromazepam—application of retrospective analysis of HRMS data. J Anal Toxicol 42:655–660. https://doi.org/10.1093/jat/bky039(open access article)CrossRefPubMed

38.

Abdul K, Hikin L, Smith P, Kurimbokus H, Ashong E, Couchman L, Morley SR (2020) Flubromazolam: detection in five post-mortem cases. Med Sci Law 60:266–269. https://doi.org/10.1177/0025802420950273CrossRefPubMed

39.

Domingo O, Roider G, Stöver A, Graw M, Musshoff F, Sachs H, Bicker W (2017) Mitragynine concentrations in two fatalities. Forensic Sci Int 271:e1–e7. https://doi.org/10.1016/j.forsciint.2016.12.020CrossRefPubMed

40.

Gevorkyan J, Kinyua J, Pearring S, Rodda LN (2021) A case series of etizolam in opioid related deaths. J Anal Toxicol. https://doi.org/10.1093/jat/bkaa146 [ahead of print]CrossRef

41.

Hockenhull J (2014) Etizolam in post-mortem cases. Imperial College London. Presented at the United Kingdom and Ireland Association of Forensic Toxicologists (UKIAFT) meeting in Leicester. https://www.imperial.ac.uk/media/imperial-college/medicine/facilities/toxicology-unit/Etizolam-poster.pdf. Accessed 15 Mar 2021

42.

Karinen R, Tuv SS, Rodge S, Peres MD, Johansen U, Frost J, Vindenes V, Øiestad ÅML (2014) Lethal poisoning with AH-7921 in combination with other substances. Forensic Sci Int 244:e21–e24. https://doi.org/10.1016/j.forsciint.2014.08.013CrossRefPubMed

43.

Kolbe V, Rentsch D, Boy D, Schmidt B, Kegler R, Büttner A (2020) The adulterated XANAX pill: a fatal intoxication with etizolam and caffeine. Int J Legal Med 134:1727–1731. https://doi.org/10.1007/s00414-020-02352-7(open access article)CrossRefPubMedPubMedCentral

44.

Liveri K, Constantinou MA, Afxentiou M, Kanari P (2016) A fatal intoxication related to MDPV and pentedrone with antipsychotic and antidepressant substances in Cyprus. Forensic Sci Int 265:160–165. https://doi.org/10.1016/j.forsciint.2016.02.017CrossRefPubMed

45.

Nakame T, Shinozuka T, Sasaki C, Ogamo A, Murakami-Hashimoto C, Irie W, Tereda M, Nakamura S, Furukawa M, Kurihara K (2008) Case report: etizolam and its major metabolites in two unnatural death cases. Forensic Sci Int 182:e1–e6. https://doi.org/10.1016/j.forsciint.2008.08.012CrossRef

46.

Papsun D, Krywanczyk A, Vose JC, Bundock EA, Logan BK (2016) Analysis of MT-45, a novel synthetic opioid in human whole blood by LC-MS-MS and its identification in a drug-related death. J Anal Toxicol 40:313–317. https://doi.org/10.1093/jat/bkw012(open access article)CrossRefPubMed

47.

Shearer K, Bryce C, Parsons M, Torrance H (2015) Phenazepam: a review of medico-legal deaths in South Scotland between 2010 and 2014. Forensic Sci Int 254:197–204. https://doi.org/10.1016/j.forsciint.2015.07.033CrossRefPubMed

48.

Tanaka N, Kinoshita H, Nishiguchi M, Jamal M, Kumihashi M, Takahashi M, Nishio H, Ameno K (2011) An autopsy case of multiple psychotropic drug poisoning. Soud Lek 56:38–39 (PMID: 21887897)PubMed

49.

Kriikku P, Rasanen I, Ojanperä I, Thelander G, Kronstrand R, Vikingsson S (2020) Femoral blood concentrations of flualprazolam in 33 postmortem cases. Forensic Sci Int 307:110101. https://doi.org/10.1016/j.forsciint.2019.110101CrossRefPubMed

50.

Krotulski AJ, Papsun DM, Noble C, Kacinko SL, Logan BK (2020) Brorphine—investigation and quantification of a new potent synthetic opioid in forensic toxicology casework using liquid chromatography-mass spectrometry. J Forensic Sci 66:664–676. https://doi.org/10.1111/1556-4029.14623CrossRefPubMed

51.

Rice K, Hikin L, Lawson A, Smith PR, Morley S (2020) Quantification of flualprazolam in blood by LC-MS-MS: a case series of nine deaths. J Anal Toxicol 45:410-416. https://doi.org/10.1093/jat/bkaa098 CrossRef

52.

Koch K, Auwärter V, Hermanns-Clausen M, Wilde M, Neukamm MA (2018) Mixed intoxication by the synthetic opioid U-47700 and the benzodiazepine flubromazepam with lethal outcome: pharmacokinetic data. Drug Test Anal 10:1336–1341. https://doi.org/10.1002/dta.2391CrossRef

53.

Noble C, Mardal M, Holm NB, Johansen SS, Linnet K (2017) In vitro studies on flubromazolam metabolism and detection of its metabolites in authentic forensic samples. Drug Test Anal 9:1182–1191. https://doi.org/10.1002/dta.2146CrossRefPubMed

54.

Corkery JM, Schifano F, Ghodse AH (2012) Phenazepam abuse in the UK: an emerging problem causing serious adverse health problems, including death. Hum Psychopharmacol 27:254–261. https://doi.org/10.1002/hup.2222CrossRefPubMed

55.

Crichton ML, Shenton CF, Drummond G, Beer LJ, Seetohul LN, Maskell PD (2015) Analysis of phenazepam and 3-hydroxyphenazepam in post-mortem fluids and tissues. Drug Test Anal 7:926–936. https://doi.org/10.1002/dta.1790CrossRefPubMed

56.

Mrozkowska J, Vinge E, Borna C (2009) Abuse of phenazepam—new phenomen in Sweden. Benzodiazepine derivative from Russia caused severe intoxication. Lakartidningen 106:516–517 (article in Swedish without an abstract, PMID: 19350785)PubMed

57.

Yip T, Martin A, Acott KS (2011) Phenazepam abuse in the West of Scotland 2009–2011. UKIAFT Annual Meeting. Aberdeen, Scotland

58.

Adamowicz P (2020) Blood concentrations of synthetic cathinones. Clin Toxicol. https://doi.org/10.1080/15563650.2020.1848100 [ahead of print]CrossRef

59.

Adamowicz P (2021) Blood concentrations of synthetic cannabinoids. Clin Toxicol 59:246–251. https://doi.org/10.1080/15563650.2020.1787429CrossRef

60.

Molina DK (2010) Handbook of forensic toxicology for medical examiners. CRC Press, Boca Raton

61.

European Monitoring Centre for Drugs and Drug Addiction (2018) Perspectives on drugs. The misuse of benzodiazepines among high-risk opioid users in Europe. Publications office of the European Union, Luxembourg. https://www.emcdda.europa.eu/topics/pods/benzodiazepines. Accessed 15 Mar 2021

62.

The National Institutes of Health (NIH) https://www.nih.gov/. Accessed 15 Mar 2021

Titel: Blood concentrations of new psychoactive substances belonging to benzodiazepine class
verfasst von: Karolina Nowak
Piotr Adamowicz
Publikationsdatum: 10.05.2021
Verlag: Springer Singapore
Erschienen in: Forensic Toxicology / Ausgabe 2/2021
Print ISSN: 1860-8965
Elektronische ISSN: 1860-8973
DOI: https://doi.org/10.1007/s11419-021-00581-y

Neu im Fachgebiet Rechtsmedizin

01.04.2024 | Forensische Traumatologie | CME

Springer Medizin

Blood concentrations of new psychoactive substances belonging to benzodiazepine class

Abstract

Purpose

Methods

Results

Conclusions

Neu im Fachgebiet Rechtsmedizin

Theoretische Grundlagen von Explosionen und Explosionsverletzungen

Auswirkungen vorgeschalteter Laborprozesse auf die Digitalisierung histologischer Schnittpräparate

Knochenmarkhistologie bei Zytopenien

Herausforderungen der Automation bei der quantitativen Auswertung von Leberbiopsien

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2021

Comparative study between active and passive exposure of methamphetamine vapor in mice

Comprehensive analytical and structural characteristics of methyl 3,3-dimethyl-2-(1-(pent-4-en-1-yl)-1H-indazole-3-carboxamido)butanoate (MDMB-4en-PINACA)

Caffeine-induced bradycardia, death, and anxiety-like behavior in zebrafish larvae

Quantification and distribution of 4-fluoroisobutyryl fentanyl (4-FiBF) in postmortem biological samples using UHPLC–QqQ-MS/MS

A potential of methoxpropamine to be a widespread recreational drug: it blocks NMDA receptors and inhibits NMDA receptor-mediated synaptic transmission in a brain preparation of mice

A fluorine turns a medicinal benzodiazepine into NPS: the case of flualprazolam

Neu im Fachgebiet Rechtsmedizin

Theoretische Grundlagen von Explosionen und Explosionsverletzungen

Auswirkungen vorgeschalteter Laborprozesse auf die Digitalisierung histologischer Schnittpräparate

Knochenmarkhistologie bei Zytopenien

Herausforderungen der Automation bei der quantitativen Auswertung von Leberbiopsien