Skip to main content

Advertisement

Log in

Fatalities associated with NPS stimulants in the Greater Cologne area

  • Original Article
  • Published:
International Journal of Legal Medicine Aims and scope Submit manuscript

Abstract

This study centres on the prevalence of new psychoactive substances (NPS) stimulant use, and its relevance as a cause of death amongst individuals between the ages of 12 and 35 in the greater Cologne area. An automated solid-phase extraction-liquid chromatography-tandem mass spectrometry method was developed for the determination of 97 stimulants in urine (including conventional stimulants, e.g. amphetamine and MDMA), of which 68 analytes were fully validated for quantification. Samples of urine or kidney tissue (in cases where urine was unavailable) of 268 deceased were collected, during autopsy, between January 2011 and May 2017 and analyzed. Blood (if available) was also investigated in cases where urine/kidney samples were tested positive for NPS. An intake of stimulants (including NPS stimulants) was proven in 50 cases. In 33 cases, only conventional stimulants were detected. A total of 17 cases were tested positive for NPS. Of the 17 NPS-positive cases, 13 were also tested positive for other conventional drugs of abuse (mostly amphetamine and MDMA). In six NPS-positive cases, at least three different NPS were proven to be ingested. Due to the determined blood concentrations, NPS was assigned as the leading cause of death, or of toxicological relevance, in the cause of death in only 5 cases. In two of the cases, NPS was judged to be a component of a multidrug poisoning, but of minor relevance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Global Synthetic Drugs Assessment (2014) Amphetamine-type stimulants and new psychoactive substances. United Nations publication, New York

    Google Scholar 

  2. European Monitoring Centre for Drugs and Drug Addiction (2018) European Drug Report 2018: trends and developments. Publications Office of the European Union, Luxembourg. https://doi.org/10.2810/688395

    Book  Google Scholar 

  3. O’Byrne PM, Kavanagh PV, McNamara SM, Stokes SM (2013) Screening of stimulants including designer drugs in urine using a liquid chromatography tandem mass spectrometry system. J Anal Toxicol 37(2):64–73. https://doi.org/10.1093/jat/bks091

    Article  CAS  PubMed  Google Scholar 

  4. Favretto D, Pascali JP, Tagliaro F (2013) New challenges and innovation in forensic toxicology: focus on the “New Psychoactive Substances”. J Chromatogr A 1287:84–95. https://doi.org/10.1016/j.chroma.2012.12.049

    Article  CAS  PubMed  Google Scholar 

  5. Pichini S, Pujadas M, Marchei E, Pellegrini M, Fiz J, Pacifici R, Zuccaro P, Farré M, de la Torre R (2008) Liquid chromatography–atmospheric pressure ionization electrospray mass spectrometry determination of “hallucinogenic designer drugs” in urine of consumers. J Pharm Biomed Anal 47(2):335–342. https://doi.org/10.1016/j.jpba.2007.12.039

    Article  CAS  PubMed  Google Scholar 

  6. Peters FT (2014) Recent developments in urinalysis of metabolites of new psychoactive substances using LC–MS. Bioanalysis 6(15):2083–2107. https://doi.org/10.4155/bio.14.168

    Article  PubMed  Google Scholar 

  7. Lehmann S, Kieliba T, Beike J, Thevis M, Mercer-Chalmers-Bender K (2017) Determination of 74 new psychoactive substances in serum using automated in-line solid-phase extraction-liquid chromatography-tandem mass spectrometry. J Chromatogr B 1064:124–138. https://doi.org/10.1016/j.jchromb.2017.09.003

    Article  CAS  Google Scholar 

  8. Uralets V, Rana S, Morgan S, Ross W (2014) Testing for designer stimulants: metabolic profiles of 16 synthetic cathinones excreted free in human urine. J Anal Toxicol 38(5):233–241. https://doi.org/10.1093/jat/bku021

    Article  CAS  PubMed  Google Scholar 

  9. Thornton SL, Gerona RR, Tomaszewski CA (2012) Psychosis from a bath salt product containing flephedrone and MDPV with serum, urine, and product quantification. J Med Toxicol 8(3):310–313. https://doi.org/10.1007/s13181-012-0232-4

    Article  PubMed  PubMed Central  Google Scholar 

  10. Helander A, Beck O, Hägerkvist R, Hultén P (2013) Identification of novel psychoactive drug use in Sweden based on laboratory analysis–initial experiences from the STRIDA project. Scand J Clin Lab Invest 73(5):400–406. https://doi.org/10.3109/00365513.2013.793817

    Article  CAS  PubMed  Google Scholar 

  11. Lusthof KJ, Oosting R, Maes A, Verschraagen M, Dijkhuizen A, Sprong AG (2011) A case of extreme agitation and death after the use of mephedrone in The Netherlands. Forensic Sci Int 206(1):e93–e95. https://doi.org/10.1016/j.forsciint.2010.12.014

    Article  PubMed  Google Scholar 

  12. Maskell PD, De Paoli G, Seneviratne C, Pounder DJ (2011) Mephedrone (4-methylmethcathinone)-related deaths. J Anal Toxicol 35(3):188–191. https://doi.org/10.1093/anatox/35.3.188

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  14. Gil D, Adamowicz P, Skulska A, Tokarczyk B, Stanaszek R (2013) Analysis of 4-MEC in biological and non-biological material—three case reports. Forensic Sci Int 228(1):e11–e15. https://doi.org/10.1016/j.forsciint.2013.03.011

    Article  CAS  PubMed  Google Scholar 

  15. Smith P, Cole R, Hamilton S, West K, Morley S, Maskell P (2016) Reporting two fatalities associated with the use of 4-methylethcathinone (4-MEC) and a review of the literature. J Anal Toxicol 40(7):553–560. https://doi.org/10.1093/jat/bkw061

    Article  CAS  PubMed  Google Scholar 

  16. Musshoff F, Padosch S, Steinborn S, Madea B (2004) Fatal blood and tissue concentrations of more than 200 drugs. Forensic Sci Int 142(2-3):161–210. https://doi.org/10.1016/j.forsciint.2004.02.017

    Article  CAS  PubMed  Google Scholar 

  17. Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remião F, Carvalho F, de Lourdes BM (2012) Toxicity of amphetamines: an update. Arch Toxicol 86(8):1167–1231. https://doi.org/10.1007/s00204-012-0815-5

    Article  CAS  PubMed  Google Scholar 

  18. Lehmann S, Schulze B, Thomas A, Kamphausen T, Thevis M, Rothschild MA, Mercer-Chalmers-Bender K (2018) Organ distribution of 4-MEC, MDPV, methoxetamine and α-PVP: comparison of QuEChERS and SPE. Forensic Toxicol 36(2):320–333. https://doi.org/10.1007/s11419-018-0408-y

    Article  CAS  Google Scholar 

  19. Gaunitz F, Schürenkamp J, Rostamzadeh A, Konkol C, Thevis M, Rothschild MA, Mercer-Chalmers-Bender K (2017) Analysis of taxine B/isotaxine B in a plasma specimen by LC–MS/MS in a case of fatal poisoning: concealed suicide by ingestion of yew (Taxus L.) leaves of a patient with a long-term history of borderline personality disorder. Forensic Toxicol 35:421–427. https://doi.org/10.1007/s11419-017-0355-z

    Article  CAS  Google Scholar 

  20. Pragst F, Herzler M, Erxleben B-T (2004) Systematic toxicological analysis by high-performance liquid chromatography with diode array detection (HPLC-DAD). Clin Chem Lab Med 42(11):1325–1340. https://doi.org/10.1515/CCLM.2004.251

    Article  CAS  PubMed  Google Scholar 

  21. Schulz M, Iwersen-Bergmann S, Andresen H, Schmoldt A (2012) Therapeutic and toxic blood concentrations of nearly 1,000 drugs and other xenobiotics. Crit Care 16:R136 (4). https://doi.org/10.1186/cc11441

    Article  PubMed  PubMed Central  Google Scholar 

  22. Andreasen MF, Telving R, Rosendal I, Eg MB, Hasselstrøm JB, Andersen LV (2015) A fatal poisoning involving 25C-NBOMe. Forensic Sci Int 251:e1–e8. https://doi.org/10.1016/j.forsciint.2015.03.012

    Article  CAS  PubMed  Google Scholar 

  23. Gee P, Schep LJ, Jensen BP, Moore G, Barrington S (2016) Case series: toxicity from 25B-NBOMe–a cluster of N-bomb cases. Clin Toxicol 54(2):141–146. https://doi.org/10.3109/15563650.2015.1115056

    Article  Google Scholar 

  24. Poklis JL, Devers KG, Arbefeville EF, Pearson JM, Houston E, Poklis A (2014) Postmortem detection of 25I-NBOMe [2-(4-iodo-2, 5-dimethoxyphenyl)-N-[(2-methoxyphenyl) methyl] ethanamine] in fluids and tissues determined by high performance liquid chromatography with tandem mass spectrometry from a traumatic death. Forensic Sci Int 234:e14–e20. https://doi.org/10.1016/j.forsciint.2013.10.015

    Article  CAS  PubMed  Google Scholar 

  25. Vevelstad M, Øiestad EL, Middelkoop G, Hasvold I, Lilleng P, Delaveris GJM, Eggen T, Mørland J, Arnestad M (2012) The PMMA epidemic in Norway: comparison of fatal and non-fatal intoxications. Forensic Sci Int 219(1):151–157. https://doi.org/10.1016/j.forsciint.2011.12.014

    Article  CAS  PubMed  Google Scholar 

  26. Nicol JJ, Yarema MC, Jones GR, Martz W, Purssell RA, MacDonald JC, Wishart I, Durigon M, Tzemis D, Buxton JA (2015) Deaths from exposure to paramethoxymethamphetamine in Alberta and British Columbia, Canada: a case series. Can Med Assoc J 3(1):E83–E90. https://doi.org/10.9778/cmajo.20140070

    Article  Google Scholar 

  27. European Monitoring Centre for Drugs and Drug Addiction (2016) Recent changes in Europe’s MDMA/ecstasy market. Publications Office of the European Union, Luxembourg. https://doi.org/10.2810/817237

    Book  Google Scholar 

  28. Rohanova M, Balikova M (2009) Studies on distribution and metabolism of para-methoxymethamphetamine (PMMA) in rats after subcutaneous administration. Toxicology 259(1):61–68. https://doi.org/10.1016/j.tox.2009.02.003

    Article  CAS  PubMed  Google Scholar 

  29. WHO Expert Committee on Drug Dependence (2015) para-Methoxymethylamphetamine (PMMA). Critical Review Report. Agenda item 5.6. https://www.who.int/medicines/access/controlled-substances/5.6_PMMA_CRev.pdf. Accessed 03 Jan 2019

  30. Elliott S, Evans J (2014) A 3-year review of new psychoactive substances in casework. Forensic Sci Int 243:55–60. https://doi.org/10.1016/j.forsciint.2014.04.017

    Article  CAS  PubMed  Google Scholar 

  31. Corkery JM, Elliott S, Schifano F, Corazza O, Ghodse AH (2012) 2-DPMP (desoxypipradrol, 2-benzhydrylpiperidine, 2-phenylmethylpiperidine) and D2PM (diphenyl-2-pyrrolidin-2-yl-methanol, diphenylprolinol): A preliminary review. Prog Neuro-Psychopharmacol Biol Psychiatry 39(2):253–258. https://doi.org/10.1016/j.pnpbp.2012.05.021

    Article  CAS  Google Scholar 

  32. Corazza O, Schifano F, Simonato P, Fergus S, Assi S, Stair J, Corkery J, Trincas G, Deluca P, Davey Z (2012) Phenomenon of new drugs on the Internet: the case of ketamine derivative methoxetamine. Hum Psychopharmacol Clin Exp 27(2):145–149. https://doi.org/10.1002/hup.1242

    Article  CAS  Google Scholar 

  33. Kriikku P, Wilhelm L, Rintatalo J, Hurme J, Kramer J, Ojanperä I (2013) Prevalence and blood concentrations of desoxypipradrol (2-DPMP) in drivers suspected of driving under the influence of drugs and in post-mortem cases. Forensic Sci Int 226(1-3):146–151. https://doi.org/10.1016/j.forsciint.2012.12.021

    Article  CAS  PubMed  Google Scholar 

  34. Chiappini S, Claridge H, Corkery JM, Goodair C, Loi B, Schifano F (2015) Methoxetamine-related deaths in the UK: an overview. Hum Psychopharmacol Clin Exp 30(4):244–248. https://doi.org/10.1002/hup.2422

    Article  Google Scholar 

  35. Adamowicz P, Zuba D (2015) Fatal intoxication with methoxetamine. J Forensic Sci 60:S264–S268. https://doi.org/10.1111/1556-4029.12594

    Article  CAS  PubMed  Google Scholar 

  36. Wikström M, Thelander G, Dahlgren M, Kronstrand R (2013) An accidental fatal intoxication with methoxetamine. J Anal Toxicol 37(1):43–46. https://doi.org/10.1093/jat/bks086

    Article  CAS  PubMed  Google Scholar 

  37. Imbert L, Boucher A, Delhome G, Cueto T, Boudinaud M, Maublanc J, Dulaurent S, Descotes J, Lachâtre G, Gaulier J-M (2014) Analytical findings of an acute intoxication after inhalation of methoxetamine. J Anal Toxicol 38(7):410–415. https://doi.org/10.1093/jat/bku052

    Article  CAS  PubMed  Google Scholar 

  38. Shields JE, Dargan PI, Wood DM, Puchnarewicz M, Davies S, Waring WS (2012) Methoxetamine associated reversible cerebellar toxicity: three cases with analytical confirmation. Clin Toxicol 50(5):438–440. https://doi.org/10.3109/15563650.2012.683437

    Article  CAS  Google Scholar 

  39. Wood DM, Davies S, Puchnarewicz M, Johnston A, Dargan PI (2012) Acute toxicity associated with the recreational use of the ketamine derivative methoxetamine. Eur J Clin Pharmacol 68(5):853–856. https://doi.org/10.1007/s00228-011-1199-9

    Article  CAS  PubMed  Google Scholar 

  40. Lehmann S, Sczyslo A, Froch-Cortis J, Rothschild MA, Thevis M, Andresen-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.2019.109959

    Article  CAS  Google Scholar 

  41. Lehmann S, Teifel D, Rothschild MA, Andresen-Streichert H (2018) Tödliche Intoxikation mit dem Designer-Opioid U-47700. Toxichem Krimtech 85(1):36

    Google Scholar 

  42. Cheney BV, Szmuszkovicz J, Lahti RA, Zichi DA (1985) Factors affecting binding of trans-N-[2-(methylamino) cyclohexyl] benzamides at the primary morphine receptor. J Med Chem 28(12):1853–1864

    Article  CAS  Google Scholar 

  43. Mohr AL, Friscia M, Papsun D, Kacinko SL, Buzby D, Logan BK (2016) Analysis of novel synthetic opioids U-47700, U-50488 and furanyl fentanyl by LC–MS/MS in postmortem casework. J Anal Toxicol 40(9):709–717. https://doi.org/10.1093/jat/bkw086

    Article  CAS  PubMed  Google Scholar 

  44. Adamowicz P, Gieroń J, Gil D, Lechowicz W, Skulska A, Tokarczyk B (2016) The prevalence of new psychoactive substances in biological material–a three-year review of casework in Poland. Drug Test Anal 8(1):63–70. https://doi.org/10.1002/dta.1924

    Article  CAS  PubMed  Google Scholar 

  45. Adamowicz P, Tokarczyk B (2016) Simple and rapid screening procedure for 143 new psychoactive substances by liquid chromatography-tandem mass spectrometry. Drug Test Anal 8(7):652–667. https://doi.org/10.1002/dta.1815

    Article  CAS  PubMed  Google Scholar 

  46. Tsujikawa K, Mikuma T, Kuwayama K, Miyaguchi H, Kanamori T, Iwata YT, Inoue H (2012) Degradation pathways of 4-methylmethcathinone in alkaline solution and stability of methcathinone analogs in various pH solutions. Forensic Sci Int 220(1):103–110. https://doi.org/10.1016/j.forsciint.2012.02.005

    Article  CAS  PubMed  Google Scholar 

  47. Al-Saffar Y, Stephanson NN, Beck O (2013) Multicomponent LC-MS/MS screening method for detection of new psychoactive drugs, legal highs, in urine-experience from the Swedish population. J Chromatogr B 930:112–120. https://doi.org/10.1016/j.jchromb.2013.04.043

    Article  CAS  Google Scholar 

  48. Concheiro M, Castaneto M, Kronstrand R, Huestis MA (2015) Simultaneous determination of 40 novel psychoactive stimulants in urine by liquid chromatography–high resolution mass spectrometry and library matching. J Chromatogr A 1397:32–42. https://doi.org/10.1016/j.chroma.2015.04.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors wish to thank Scientific Instruments Manufacturer GmbH (Oberhausen, Germany) for generously providing the ITSP-SPE system for this research. We thank Dr. June Mercer-Chalmers-Bender for editorial support. This work was supported by the Federal Ministry for Economic Affairs and Energy on the basis of a decision by the German Bundestag, grand no. KF2429613MD3.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Katja Mercer-Chalmers-Bender.

Ethics declarations

Ethical approval

All experiments comply with the current laws of the Federal Republic of Germany. All performed analytical tests were part of the state prosecutors’ requested investigation on the cause of death, and are therefore not subject to the requirements for ethical approval. The state prosecutor gave his approval to publish the results under the condition of complete anonymization of individual data. The article does not contain any studies on animals performed by any of the authors.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 119 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lehmann, S., Kieliba, T., Thevis, M. et al. Fatalities associated with NPS stimulants in the Greater Cologne area. Int J Legal Med 134, 229–241 (2020). https://doi.org/10.1007/s00414-019-02193-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00414-019-02193-z

Keywords

Navigation