Ewa Tomczak and Mateusz Kacper Woźniak contributed equally as first authors.
The 4-chloromethcathinone (4-CMC) is a synthetic derivative of cathinone and belongs to new psychoactive substances. Neither data on the effects of 4-CMC on the human body, nor on nontoxic, toxic and lethal concentrations in biological materials have been published in the literature. This paper describes the results of an analysis of the blood concentrations of 4-CMC determined in 15 forensic cases related to nonfatal intoxication including driving under the influence, and fatalities including overdoses, suicide and traffic accidents.
A new method for the quantification of 4-CMC using gas chromatography–mass spectrometry (GC–MS) was developed. The symptoms of 4-CMC use were also studied based on an analysis of the documents prepared during the collection of samples or at autopsies.
The limits of detection and quantification of the method for blood samples were 0.3 and 1 ng/mL, respectively. The calibration curve was linear in the studied concentration range (1–500 ng/mL) with the correlation coefficient at 0.9979. The extraction recoveries varied in the range of 94.3–98.8%. The accuracy and precision were acceptable. The determined concentrations in nonfatal cases ranged from 1.3 to 75.3 ng/mL, and in fatalities from 56.2 to 1870 ng/mL.
Our study can assist in the recognition of the possible effects caused by 4-CMC and can be helpful during the preparation of forensic toxicological opinions for courts of law. The validation parameters indicate the sensitivity and accuracy of the method. This is the first work presenting a validated method for the determination of 4-CMC in blood samples by GC–MS.
United Nations Office on Drugs and Crime (2014) Global synthetic drugs assessment: amphetamine-type stimulants and new psychoactive substances. United Nations, New York. https://www.unodc.org/documents/scientific/2014_Global_Synthetic_Drugs_Assessment_web.pdf. Accessed 10 Jan 2018
European Monitoring Centre for Drugs and Drug Addiction (2015) New psychoactive substances in Europe: an update from the EU early warning system. Publications Office of the European Union, Louxemburg. http://www.emcdda.europa.eu/attachements.cfm/att_235958_EN_TD0415135ENN.pdf. Accessed 10 Jan 2018
United Nations Office on Drugs and Crime (2016) World drug report. United Nations, New York. http://www.unodc.org/doc/wdr2016/WORLD_DRUG_REPORT_2016_web.pdf. Accessed 10 Jan 2018
Taschwer M, Weiß JA, Kunert O, Schmid MG (2014) Analysis and characterization of the novel psychoactive drug 4-chloromethcathinone (clephedrone). Forensic Sci Int 244:e56–e59. https://doi.org/10.1016/j.forsciint.2014.09.007CrossRefPubMed
Klavž J, Gorenjak M, Marinšek M (2016) Suicide attempt with a mix of synthetic cannabinoids and synthetic cathinones: case report of non-fatal intoxication with AB-CHMINACA, AB-FUBINACA, alpha-PHP, alpha-PVP and 4-CMC. Forensic Sci Int 265:121–124. https://doi.org/10.1016/j.forsciint.2016.01.018CrossRefPubMed
Zawiadomienie o drukowaniu i rozpowszechnianiu środków do podawania nie farmaceutycznych środków odurzających i leków psychotropowych. http://www.sfda.gov.cn/WS01/CL0056/130753.html. Accessed 18 Feb 2018
Commonwealth of Virginia (2018) Administrative code. https://law.lis.virginia.gov/admincode/title18/agency110/chapter20/section322/. Accessed 10 Jan 2018
Wiergowski M, Aszyk J, Kaliszan M, Wilczewska K, Anand JS, Kot-Wasik A, Jankowski Z (2017) Identification of novel psychoactive substances 25B-NBOMe and 4-CMC in biological material using HPLC-Q-TOF-MS and their quantification in blood using UPLC-MS/MS in case of severe intoxications. J Chromatogr B 1041–1042:1–10. https://doi.org/10.1016/j.jchromb.2016.12.018CrossRef
Drugs-Forum (2017). https://drugs-forum.com/threads/4-cmc-clephedrone-4-chloromethcathinone-drug-info.63250/. Accessed 10 Jan 2018
US Food and Drug Administration (2001) Guidance for industry: bioanalytical method validation. Guidance for industry: bioanalytical method validation. http://www.labcompliance.de/documents/FDA/FDA-Others/Laboratory/f-507-bioanalytical-4252fnl.pdf. Accessed 10 Jan 2018
US Food and Drug Administration (1996) Guidance for industry: Q2B validation of analytical procedures: methodology. https://www.fda.gov/downloads/drugs/guidances/ucm073384.pdf. Accessed 10 Jan 2018
Rajski Ł, Lozano A, Uclés A, Ferrer C, Fernandez-Alba AR (2013) Determination of pesticide residues in high oil vegetal commodities by using various multi-residue methods and clean-ups followed by liquid chromatography tandem mass spectrometry. J Chromatogr A 1304:109–120. https://doi.org/10.1016/j.chroma.2013.06.070CrossRefPubMed
Główny Inspektorat Sanitarny, Departament Nadzoru nad Środkami Zastępczymi (2017) Raport Głównego Inspektoratu Sanitarnego w sprawie środków zastępczych i nowych substancji psychoaktywnych-STOP dopalaczom 2015–2016. Warszawa. http://pis.lodz.pl/data/other/raport_dopalcze_201516.pdf. Accessed 10 Jan 2018
Vaiano F, Busardo FP, Palumbo D, Kyriakou C, Fioravanti A, Catalani V, Mari F, Bertol E (2016) A novel screening method for 64 new psychoactive substances and 5 amphetamines in blood by LC-MS/MS and application to real cases. J Pharm Biomed Anal 129:441–449. https://doi.org/10.1016/j.jpba.2016.07.009CrossRefPubMed
Kim SY, Kim JY, Kwon W, In MK, Kim YE, Paeng K-J (2013) Method development for simultaneous determination of amphetamine type stimulants and cannabinoids in urine using GC–MS. Microchem J 110:326–333. https://doi.org/10.1016/j.microc.2013.04.004CrossRef
Banks ML, Worst TJ, Sprague JE (2014) Synthetic cathinones and amphetamine analogues: what’s the rave about? J Emerg Med 46:632–642. https://doi.org/10.1016/j.jemermed.2013.11.104CrossRefPubMedPubMedCentral
- Blood concentrations of a new psychoactive substance 4-chloromethcathinone (4-CMC) determined in 15 forensic cases
Mateusz Kacper Woźniak
- Springer Japan