Organ distribution of 4-MEC, MDPV, methoxetamine and α-PVP: comparison of QuEChERS and SPE

Springer Science and Business Media LLC - Tập 36 - Trang 320-333 - 2018
Sabrina Lehmann1, Bastian Schulze1, Andreas Thomas2, Thomas Kamphausen1, Mario Thevis2, Markus A. Rothschild1, Katja Mercer-Chalmers-Bender1,3
1Institute of Legal Medicine, Faculty of Medicine, University of Cologne, Cologne, Germany
2Institute of Biochemistry, German Sport University Cologne, Cologne, Germany
3Institute of Forensic Medicine, University of Basel, Health Department Basel, Basel, Switzerland

Tóm tắt

An organ distribution investigation was carried out on two deceased (A and B) who consumed 4-methylethcathinone (4-MEC), methylenedioxypyrovalerone (MDPV), methoxetamine (MXE) and α-pyrrolidinopentiophenone (α-PVP). The detection of the aforementioned drugs in the specimens was performed on a liquid chromatography–tandem mass spectrometry system. Two different extraction methods were compared with each other—a quick, easy, cheap, effective, rugged and safe (QuEChERS) approach and an automated Instrument Top Sample Preparation-solid phase extraction (ITSP-SPE). Standard addition method was used to quantify the drugs. 4-MEC, MDPV and MXE were detected in all collected tissues and body fluids of the two deceased. α-PVP was also detectable in deceased A. Deceased A showed femoral blood concentrations of 97 µg/L 4-MEC, 396 µg/L MDPV, 295 µg/L MXE and 4 µg/L α-PVP measured after extraction by QuEChERS and 118 µg/L 4-MEC, 342 µg/L MDPV, 385 µg/L MXE and 4 µg/L α-PVP measured after ITSP-SPE. Deceased B revealed heart blood concentrations of 8 µg/L 4-MEC, 3 µg/L MDPV and 2 µg/L MXE after extraction by QuEChERS and 8 µg/L 4-MEC and 1 µg/L MXE after ITSP-SPE. Both preparation techniques were suitable for quantifying NPS in organ tissues and body fluids. With respect to the autopsy findings, the cause of death of deceased A was determined to be an acute intoxication with NPS. No certain cause of death could be ascertained for deceased B.

Tài liệu tham khảo

United Nations Office on Drugs and Crime (UNODC) (2016) New psychoactive substances: overview of trends, challenges and legal approaches. vol E/CN.7/2016/CRP.2 Guirguis A, Corkery JM, Stair JL, Kirton SB, Zloh M, Schifano F (2017) Intended and unintended use of cathinone mixtures. Hum Psychopharmacol Clin Exp 32:1–17 US Drug Enforcement Administration (2014) Schedules of controlled substances: temporary placement of 10 synthetic cathinones into schedule I. Fed Regist 79:12938–12943 Ross EA, Watson M, Goldberger B (2011) “Bath salts” intoxication. N Engl J Med 365:967–968 Spiller HA, Ryan ML, Weston RG, Jansen J (2011) Clinical experience with and analytical confirmation of “bath salts” and “legal highs”(synthetic cathinones) in the United States. Clin Toxicol 49:499–505 Giannotti G, Canazza I, Caffino L, Bilel S, Ossato A, Fumagalli F, Marti M (2017) The cathinones MDPV and α-PVP elicit different behavioral and molecular effects following acute exposure. Neurotox Res 32:594–602 Marusich JA, Antonazzo KR, Wiley JL, Blough BE, Partilla JS, Baumann MH (2014) Pharmacology of novel synthetic stimulants structurally related to the “bath salts” constituent 3, 4-methylenedioxypyrovalerone (MDPV). Neuropharmacology 87:206–213 US Drug Enforcement Administration (2011) Schedules of controlled substances: temporary placement of three synthetic cathinones in Schedule I. Fed Regist 76:65371–65375 World Health Organization (2014) 4-Methylethcathinone (4-MEC): critical review report. Expert Committee on Drug Dependence 36th ECDD Agenda item 4.3 Winstock AR, Mitcheson LR, Deluca P, Davey Z, Corazza O, Schifano F (2011) Mephedrone, new kid for the chop? Addiction 106:154–161 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:e11–e15 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 27:145–149 Kumlien E, Hartvig P, Valind S, Øye I, Tedroff J, Långström B (1999) NMDA-receptor activity visualized with (S)-[N-methyl-11C] ketamine and positron emission tomography in patients with medial temporal lobe epilepsy. Epilepsia 40:30–37 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 Hasegawa K, Wurita A, Minakata K, Gonmori K, Nozawa H, Yamagishi I, Watanabe K, Suzuki O (2015) Postmortem distribution of AB-CHMINACA, 5-fluoro-AMB, and diphenidine in body fluids and solid tissues in a fatal poisoning case: usefulness of adipose tissue for detection of the drugs in unchanged forms. Forensic Toxicol 33:45–53 Anastassiades M, Lehotay SJ, Štajnbaher D, Schenck FJ (2003) Fast and easy multiresidue method employing acetonitrile extraction/partitioning and “dispersive solid-phase extraction” for the determination of pesticide residues in produce. J AOAC Int 86:412–431 Kudo K, Usumoto Y, Kikura-Hanajiri R, Sameshima N, Tsuji A, Ikeda N (2015) A fatal case of poisoning related to new cathinone designer drugs, 4-methoxy PV8, PV9, and 4-methoxy PV9, and a dissociative agent, diphenidine. Leg Med 17:421–426 Usui K, Aramaki T, Hashiyada M, Hayashizaki Y, Funayama M (2014) Quantitative analysis of 3, 4-dimethylmethcathinone in blood and urine by liquid chromatography–tandem mass spectrometry in a fatal case. Leg Med 16:222–226 Usui K, Hayashizaki Y, Hashiyada M, Funayama M (2012) Rapid drug extraction from human whole blood using a modified QuEChERS extraction method. Leg Med 14:286–296 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 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 42:1325–1340 Schulz M, Iwersen-Bergmann S, Andresen H, Schmoldt A (2012) Therapeutic and toxic blood concentrations of nearly 1000 drugs and other xenobiotics. Crit Care 16:R136. https://doi.org/10.1186/cc11441 Thomas A, Schänzer W, Thevis M (2014) Determination of human insulin and its analogues in human blood using liquid chromatography coupled to ion mobility mass spectrometry (LC–IM-MS). Drug Test Anal 6:1125–1132 Cuadros-Rodríguez L, Bagur-González MG, Sánchez-Vinas M, González-Casado A, Gómez-Sáez AM (2007) Principles of analytical calibration/quantification for the separation sciences. J Chromatogr A 1158:33–46 Paul L, Musshoff F, Aebi B, Auwärter V, Krämer T, Peters F, Skopp G, Aderjan R, Herbold M, Schmitt G (2009) Richtlinie der GTFCh zur Qualitätssicherung bei forensisch-toxikologischen Untersuchungen. Toxichem Krimtech 76:142–176 Peters FT, Drummer OH, Musshoff F (2007) Validation of new methods. Forensic Sci Int 165:216–224 Matuszewski B, Constanzer M, Chavez-Eng C (2003) Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC–MS/MS. Anal Chem 75:3019–3030 Peters F, Musshoff F, Kraemer T (2009) Anhang B. Richtlinie der GTFCh zur Qualitätssicherung bei forensisch-toxikologischen Untersuchungen Anforderungen an die Validierung von Analysenmethoden. Toxichem Krimtech 76:185–208 European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) (2014) Europol Joint Report on a new psychoactive substance: MDPV (3,4-methylenedioxypyrovalerone). Publications Office of the European Union, Luxembourg. https://doi.org/10.2810/24085 Katselou M, Papoutsis I, Nikolaou P, Spiliopoulou C, Athanaselis S (2016) α-PVP (“flakka”): a new synthetic cathinone invades the drug arena. Forensic Toxicol 34:41–50 Araújo AM, Valente MJ, Carvalho M, Da Silva DD, Gaspar H, Carvalho F, de Lourdes Bastos M, De Pinho PG (2015) Raising awareness of new psychoactive substances: chemical analysis and in vitro toxicity screening of ‘legal high’ packages containing synthetic cathinones. Arch Toxicol 89:757–771 Leffler AM, Smith PB, de Armas A, Dorman FL (2014) The analytical investigation of synthetic street drugs containing cathinone analogs. Forensic Sci Int 234:50–56 Wyman JF, Lavins ES, Engelhart D, Armstrong EJ, Snell KD, Boggs PD, Taylor SM, Norris RN, Miller FP (2013) Postmortem tissue distribution of MDPV following lethal intoxication by “bath salts”. J Anal Toxicol 37:182–185 Cawrse BM, Levine B, Jufer RA, Fowler DR, Vorce SP, Dickson AJ, Holler JM (2012) Distribution of methylone in four postmortem cases. J Anal Toxicol 36:434–439 Wright TH, Cline-Parhamovich K, Lajoie D, Parsons L, Dunn M, Ferslew KE (2013) Deaths involving methylenedioxypyrovalerone (MDPV) in upper east Tennessee. J Forensic Sci 58:1558–1562 Murray BL, Murphy CM, Beuhler MC (2012) Death following recreational use of designer drug “bath salts” containing 3, 4-methylenedioxypyrovalerone (MDPV). J Med Toxicol 8:69–75 Hasegawa K, Suzuki O, Wurita A, Minakata K, Yamagishi I, Nozawa H, Gonmori K, Watanabe K (2014) Postmortem distribution of α-pyrrolidinovalerophenone and its metabolite in body fluids and solid tissues in a fatal poisoning case measured by LC–MS–MS with the standard addition method. Forensic Toxicol 32:225–234 Potocka-Banaś B, Janus T, Majdanik S, Banaś T, Dembińska T, Borowiak K (2017) Fatal intoxication with α-PVP, a synthetic cathinone derivative. J Forensic Sci 62:553–556 Saito T, Namera A, Osawa M, Aoki H, Inokuchi S (2013) SPME–GC–MS analysis of α-pyrrolidinovaleorophenone in blood in a fatal poisoning case. Forensic Toxicol 31:328–332 Knoy JL, Peterson BL, Couper FJ (2014) Suspected impaired driving case involving α-pyrrolidinovalerophenone, methylone and ethylone. J Anal Toxicol 38:615–617 Soh YNA, Elliott S (2014) An investigation of the stability of emerging new psychoactive substances. Drug Test Anal 6:696–704 Skopp G (2004) Preanalytic aspects in postmortem toxicology. Forensic Sci Int 142:75–100 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 40:553–560 Hajkova K, Jurasek B, Sykora D, Palenicek T, Miksatkova P, Kuchar M (2016) Salting-out-assisted liquid–liquid extraction as a suitable approach for determination of methoxetamine in large sets of tissue samples. Anal Bioanal Chem 408:1171–1181 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 38:410–415 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 50:438–440 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 68:853–856 Adamowicz P, Zuba D (2015) Fatal intoxication with methoxetamine. J Forensic Sci 60:S264–S268 Wikström M, Thelander G, Dahlgren M, Kronstrand R (2013) An accidental fatal intoxication with methoxetamine. J Anal Toxicol 37:43–46 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 30:244–248 Wunder C, Kauert GF, Toennes SW (2014) Factors leading to the degradation/loss of insulin in postmortem blood samples. Forensic Sci Int 241:173–177