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Review Article

Synthetic cathinone pharmacokinetics, analytical methods, and toxicological findings from human performance and postmortem cases

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Pages 237-265 | Received 24 Mar 2016, Accepted 06 May 2016, Published online: 01 Jun 2016

References

  • Adamowicz P, Gil D, Skulska A, Tokarczyk B. (2013a). Analysis of MDPV in blood – determination and interpretation. J Anal Toxicol 37:308–312.
  • Adamowicz P, Tokarczyk B. (2015). Simple and rapid screening procedure for 143 new psychoactive substances by liquid chromatography-tandem mass spectrometry. Drug Test Anal. [Epub ahead of print]. doi: 10.1002/dta.1815.
  • Adamowicz P, Tokarczyk B, Stanaszek R, Slopianka M. (2013b). Fatal mephedrone intoxication – a case report. J Anal Toxicol 37:37–42.
  • 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 Analyt Technol Biomed Life Sci 930:112–120.
  • Amaratunga P, Lorenz Lemberg B, Lemberg D. (2013). Quantitative measurement of synthetic cathinones in oral fluid. J Anal Toxicol 37:622–628.
  • Ambach L, Hernandez Redondo A, Konig S, Weinmann W. (2014). Rapid and simple LC-MS/MS screening of 64 novel psychoactive substances using dried blood spots. Drug Test Anal 6:367–375.
  • Anizan S, Concheiro M, Lehner KR, et al. (2016). Linear pharmacokinetics of 3,4-methylenedioxypyrovalerone (MDPV) and its metabolites in the rat: relationship to pharmacodynamic effects. Addict Biol 21:339–347.
  • Anizan S, Ellefsen K, Concheiro M, et al. (2014). 3,4-Methylenedioxypyrovalerone (MDPV) and metabolites quantification in human and rat plasma by liquid chromatography–high resolution mass spectrometry. Anal Chim Acta 827:54–63.
  • Archer RP. (2009). Fluoromethcathinone, a new substance of abuse. Forensic Sci Int 185:10–20.
  • Balikova M, Zidkova M, Oktabec Z, et al. (2013). The abuse of 3,4-methylenedioxypyrrolidinobutiophenone (MDPBP): A case report. J Forensic Toxiciol Pharmacol 2:1–4.
  • Baumann MH, Ayestas MA, Jr., Partilla JS, et al. (2012). The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. Neuropsychopharmacology 37:1192–1203.
  • Baumann MH, Partilla JS, Lehner KR. (2013a). Psychoactive “ ‘bath salts’: not so soothing”. Eur J Pharmacol 698:1–5.
  • Baumann MH, Partilla JS, Lehner KR, et al. (2013b). Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive ‘bath salts’ products. Neuropsychopharmacology 38:552–562.
  • Bertol E, Mari F, Boscolo Berto R, et al. (2014). A mixed MDPV and benzodiazepine intoxication in a chronic drug abuser: Determination of MDPV metabolites by LC-HRMS and discussion of the case. Forensic Sci Int 243:149–155.
  • Borek HA, Holstege CP. (2012). Hyperthermia and multiorgan failure after abuse of “ ‘bath salts’ containing 3,4-methylenedioxypyrovalerone”. Ann Emerg Med 60:103–105.
  • Busardo FP, Kyriakou C, Tittarelli R, et al. (2015). Assessment of the stability of mephedrone in ante-mortem and post-mortem blood specimens. Forensic Sci Int 256:28–37.
  • Carbone PN, Carbone DL, Carstairs SD, Luzi SA. (2013). Sudden cardiac death associated with methylone use. Am J Forensic Med Pathol 34:26–28.
  • Cawrse BM, Levine B, Jufer RA, et al. (2012). Distribution of methylone in four postmortem cases. J Anal Toxicol 36:434–439.
  • Concheiro M, Anizan S, Ellefsen K, Huestis MA. (2013). Simultaneous quantification of 28 synthetic cathinones and metabolites in urine by liquid chromatography-high resolution mass spectrometry. Anal Bioanal Chem 405:9437–9448.
  • 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.
  • Coppola M, Mondola R. (2012). 3,4-Methylenedioxypyrovalerone (MDPV): Chemistry, pharmacology and toxicology of a new designer drug of abuse marketed online. Toxicol Lett 208:12–15.
  • Cosbey SH, Peters KL, Quinn A, Bentley A. (2013). Mephedrone (methylmethcathinone) in toxicology casework: A Northern Ireland perspective. J Anal Toxicol 37:74–82.
  • Dargan PI, Sedefov R, Gallegos A, Wood DM. (2011). The pharmacology and toxicology of the synthetic cathinone mephedrone (4-methylmethcathinone). Drug Test Anal 3:454–463.
  • De Castro A, Lendoiro E, Fernandez-Vega H, et al. (2014). Liquid chromatography tandem mass spectrometry determination of selected synthetic cathinones and two piperazines in oral fluid. Cross reactivity study with an on-site immunoassay device. J Chromatogr A 1374:93–101.
  • Derungs A, Schietzel S, Meyer MR, et al. (2011). Sympathomimetic toxicity in a case of analytically confirmed recreational use of naphyrone (naphthylpyrovalerone). Clin Toxicol (Phila) 49:691–693.
  • Dickson AJ, Vorce SP, Levine B, Past MR. (2010). Multiple-drug toxicity caused by the coadministration of 4-methylmethcathinone (mephedrone) and heroin. J Anal Toxicol 34:162–168.
  • Dragogna F, Oldani L, Buoli M, Altamura AC. (2014). A case of severe psychosis induced by novel recreational drugs. F1000Res 3:21.
  • Ellefsen KN, Anizan S, Castaneto MS, et al. (2014). Validation of the only commercially available immunoassay for synthetic cathinones in urine: Randox drugs of abuse V biochip array technology. Drug Test Anal 6:728–738.
  • Ellefsen K, Concheiro M, Suzuki M, et al. (2015). Quantification of methylone and metabolites in rat and human plasma by liquid chromatography-tandem mass spectrometry. Forensic Toxicol 33:202–212.
  • Ellefsen K, Wohlfarth A, Swortwood M, et al. (2016). 4-Methoxy-α-PVP: In silico prediction, metabolic stability, and metabolite identification by human hepatocyte incubation and high-resolution mass spectrometry. Forensic Toxicol 34:61–75.
  • Eshleman AJ, Wolfrum KM, Hatfield MG, et al. (2013). Substituted methcathinones differ in transporter and receptor interactions. Biochem Pharmacol 85:1803–1815.
  • European Centre for Drugs and Drug Addiction (EMCDDA). (2011). Risk assessment report of a new pyschoactive substance- 4-methylmethcathinone (mephedrone). Lisbon, Portugal.
  • European Centre for Drugs and Drug Addiction (EMCDDA). (2015a). New psychoactive substances in Europe – An update from the EU Early Warning System. doi:10.2810/372415.
  • European Centre for Drugs and Drug Addiction (EMCDDA). (2015b). Perspective on Drugs: Injection of Synthetic Cathinones [Online]. Available: http://www.emcdda.europa.eu/topics/pods/synthetic-cathinones-injection#panel1 [last accessed 23 Feb 2016].
  • Froberg BA, Levine M, Beuhler MC, et al. (2015). Acute methylenedioxypyrovalerone toxicity. J Med Toxicol 11:185–194.
  • Gil D, Adamowicz P, Skulska A, et al. (2013). Analysis of 4-MEC in biological and non-biological material – Three case reports. Forensic Sci Int 228:e11–e15.
  • Hagan KS, Reidy L. (2015). Detection of synthetic cathinones in victims of sexual assault. Forensic Sci Int 257:71–75.
  • Hasegawa K, Suzuki O, Wurita A, et al. (2014a). 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.
  • Hasegawa K, Wurita A, Minakata K, et al. (2014b). Identification and quantitation of a new cathinone designer drug PV9 in an ‘‘aroma liquid’’ product, antemortem whole blood and urine specimens, and a postmortem whole blood specimen in a fatal poisoning case. Forensic Toxicol 32:243–250.
  • Helfer AG, Turcant A, Boels D, et al. (2015). Elucidation of the metabolites of the novel psychoactive substance 4-methyl-N-ethyl-cathinone (4-MEC) in human urine and pooled liver microsomes by GC-MS and LC-HR-MS/MS techniques and of its detectability by GC-MS or LC-MS(n) standard screening approaches. Drug Test Anal 7:368–375.
  • Hill SL, Thomas SH. (2011). Clinical toxicology of newer recreational drugs. Clin Toxicol (Phila) 49:705–719.
  • Iversen L, Gibbons S, Treble R, et al. (2013). Neurochemical profiles of some novel psychoactive substances. Eur J Pharmacol 700:147–151.
  • James D, Adams RD, Spears R, et al. (2011). Clinical characteristics of mephedrone toxicity reported to the U.K. National Poisons Information Service. Emerg Med J 28:686–689.
  • John ME, Thomas-Rozea C, Hahn D. (2014). Bath salts abuse leading to new onset psychosis and potential for violence. Clin Schizophr Relat Psychoses. [Epub ahead of print]. doi: 10.3371/CSRP.JORO.061314.
  • Johnson RD, Botch-Jones SR. (2013). The stability of four designer drugs: MDPV, mephedrone, BZP and TFMPP in three biological matrices under various storage conditions. J Anal Toxicol 37:51–55.
  • Kaizaki A, Tanaka S, Numazawa S. (2014). New recreational drug 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (alpha-PVP) activates central nervous system via dopaminergic neuron. J Toxicol Sci 39:1–6.
  • Kamata HT, Shima N, Zaitsu K, et al. (2006). Metabolism of the recently encountered designer drug, methylone, in humans and rats. Xenobiotica 36:709–723.
  • Kasick DP, Mcknight CA, Klisovic E. (2012). “ ‘Bath salt’ ingestion leading to severe intoxication delirium: Two cases and a brief review of the emergence of mephedrone use”. Am J Drug Alcohol Abuse 38:176–180.
  • Katagi M. (2010). Metabolism and forensic toxicological analyses of the extensively abused designer drug methylone. TIAFT Bull 40:30–35.
  • Kerrigan S, Savage M, Cavazos C, Bella P. (2016). Thermal degradation of synthetic cathinones: implications for forensic toxicology. J Anal Toxicol 40:1–11.
  • Kesha K, Boggs CL, Ripple MG, et al. (2013). Methylenedioxypyrovalerone (“(‘bath salts’), related death: Case report and review of the literature”). J Forensic Sci 58:1654–1659.
  • Khreit OI, Grant MH, Zhang T, et al. (2013). Elucidation of the Phase I and Phase II metabolic pathways of (+/-)-4’-methylmethcathinone (4-MMC) and (+/−)-4’-(trifluoromethyl)methcathinone (4-TFMMC) in rat liver hepatocytes using LC-MS and LC-MS(2). J Pharm Biomed Anal 72:177–185.
  • Khullar V, Jain A, Sattari M. (2014). Emergence of new classes of recreational drugs-synthetic cannabinoids and cathinones. J Gen Intern Med 29:1200–1204.
  • Knoy JL, Peterson BL, Couper FJ. (2014). Suspected impaired driving case involving α-pyrrolidinovalerophenone, methylone and ethylone. J Anal Toxicol 38:615–617.
  • Kovacs K, Toth AR, Kereszty EM. (2012). A new designer drug: methylone related death. Orv Hetil 153:271–276.
  • Kriikku P, Wilhelm L, Schwarz O, Rintatalo J. (2011). New designer drug of abuse: 3,4-Methylenedioxypyrovalerone (MDPV). Findings from apprehended drivers in Finland. Forensic Sci Int 210:195–200.
  • Lee D, Chronister CW, Hoyer J, Goldberger BA. (2015). Ethylone-related deaths: Toxicological findings. J Anal Toxicol 39:567–571.
  • Liechti M. (2015). Novel psychoactive substances (designer drugs): overview and pharmacology of modulators of monoamine signaling. Swiss Med Wkly 145:w14043.
  • Loi B, Corkery JM, Claridge H, et al. (2015). Deaths of individuals aged 16–24 years in the UK after using mephedrone. Hum Psychopharmacol 30:225–232.
  • Lopez-Arnau R, Martinez-Clemente J, Pubill D, et al. (2012). Comparative neuropharmacology of three psychostimulant cathinone derivatives: Butylone, mephedrone and methylone. Br J Pharmacol 167:407–420.
  • Lopez-Arnau R, Martinez-Clemente J, Carbo M, et al. (2013). An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as “bath salts”. Prog Neuropsychopharmacol Biol Psychiatry 45:64–72.
  • Lusthof KJ, Oosting R, Maes A, et al. (2011). A case of extreme agitation and death after the use of mephedrone in The Netherlands. Forensic Sci Int 206:e93–e95.
  • Maas A, Wippich C, Madea B, Hess C. (2015). Driving under the influence of synthetic phenethylamines: A case series. Int J Legal Med 129:997–1003.
  • Macher AM, Penders TM. (2013). False-positive phencyclidine immunoassay results caused by 3,4-methylenedioxypyrovalerone (MDPV). Drug Test Anal 5:130–132.
  • Mangold AR, Bravo TP, Traub SJ, et al. (2014). Flashback phenomenon and residual neurological deficits after the use of “ ‘bath salt‘ 3, 4-methylenedioxypyrovalerone”. World J Emerg Med 5:63–66.
  • Marinetti LJ, Antonides HM. (2013). Analysis of synthetic cathinones commonly found in bath salts in human performance and postmortem toxicology: Method development, drug distribution and interpretation of results. J Anal Toxicol 37:135–146.
  • Martinez-Clemente J, Lopez-Arnau R, Carbo M, et al. (2013). Mephedrone pharmacokinetics after intravenous and oral administration in rats: Relation to pharmacodynamics. Psychopharmacology (Berl) 229:295–306.
  • Marusich JA, Antonazzo KR, Wiley JL, et al. (2014). Pharmacology of novel synthetic stimulants structurally related to the “bath salts” constituent 3,4-methylenedioxypyrovalerone (MDPV). Neuropharmacology 87:206–213.
  • Maskell PD, De Paoli G, Seneviratne C, Pounder DJ. (2011). Mephedrone (4-methylmethcathinone)-related deaths. J Anal Toxicol 35:188–191.
  • McIntyre IM, Hamm CE, Aldridge L, Nelson CL. (2013). Acute methylone intoxication in an accidental drowning – A case report. Forensic Sci Int 231:e1–e3.
  • McIntyre IM, Hamm CE, Sherrard JL, et al. (2015). Acute 3,4-methylenedioxy-N-ethylcathinone (ethylone) intoxication and related fatality: A case report with postmortem concentrations. J Anal Toxicol 39:225–228.
  • Meyer MR, Du P, Schuster F, Maurer HH. (2010a). Studies on the metabolism of the α-pyrrolidinophenone designer drug methylenedioxy-pyrovalerone (MDPV) in rat and human urine and human liver microsomes using GC–MS and LC–high-resolution MS and its detectability in urine by GC–MS. J Mass Spectrom 45:1426–1442.
  • Meyer MR, Wilhelm J, Peters FT, Maurer HH. (2010b). Beta-keto amphetamines: studies on the metabolism of the designer drug mephedrone and toxicological detection of mephedrone, butylone, and methylone in urine using gas chromatography-mass spectrometry. Anal Bioanal Chem 397:1225–1233.
  • Meyer MR, Vollmar C, Schwaninger AE, et al. (2012). New cathinone-derived designer drugs 3-bromomethcathinone and 3-fluoromethcathinone: Studies on their metabolism in rat urine and human liver microsomes using GC–MS and LC–high-resolution MS and their detectability in urine. J Mass Spectrom 47:253–262.
  • Meyer MR, Prosser D, Maurer HH. (2013). Studies on the metabolism and detectability of the designer drug β-naphyrone in rat urine using GC-MS and LC-HR-MS/MS. Drug Test Anal 5:259–265.
  • Meyer MR, Mauer S, Meyer GMJ, et al. (2014). The in vivo and in vitro metabolism and the detectability in urine of 3′,4′-methylenedioxy-alpha-pyrrolidinobutyrophenone (MDPBP), a new pyrrolidinophenone-type designer drug, studied by GC-MS and LC-MSn. Drug Test Anal 6:746–756.
  • Minakata K, Yamagishi I, Nozawa H, et al. (2015). Determination of new pyrrolidino cathinone derivatives, PVT, F-PVP, MPHP, PV8, PV9 and F-PV9, in human blood by MALDI-Q-TOF mass spectrometry. Forensic Toxicol 33:148–154.
  • Mueller DM, Rentsch KM. (2012). Generation of metabolites by an automated online metabolism method using human liver microsomes with subsequent identification by LC-MS(n), and metabolism of 11 cathinones. Anal Bioanal Chem 402:2141–2151.
  • 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.
  • Namera A, Konuma K, Kawamura M, et al. (2014). Time-course profile of urinary excretion of intravenously administered α-pyrrolidinovalerophenone and α-pyrrolidinobutiophenone in a human. Forensic Toxicol 32:68–74.
  • National Conference of State Legislatures (NCSL). (2015). Synthetic Drug Threats. [Online]. Available: http://www.ncsl.org/research/civil-and-criminal-justice/synthetic-drug-threats.aspx [last accessed 14 Sep 2015].
  • Negreira N, Erratico C, Kosjek T, et al. (2015). In vitro Phase I and Phase II metabolism of alpha-pyrrolidinovalerophenone (alpha-PVP), methylenedioxypyrovalerone (MDPV) and methedrone by human liver microsomes and human liver cytosol. Anal Bioanal Chem 407:5803–5816.
  • Odoardi S, Fisichella M, Romolo FS, Strano-Rossi S. (2015). High-throughput screening for new psychoactive substances (NPS) in whole blood by DLLME extraction and UHPLC-MS/MS analysis. J Chromatogr B: Anal Technol Biomed Life Sci 1000:57–68.
  • Palamar JJ, Martins SS, Su MK, Ompad DC. (2015). Self-reported use of novel psychoactive substances in a US nationally representative survey: Prevalence, correlates, and a call for new survey methods to prevent underreporting. Drug Alcohol Depend 156:112–119.
  • Pasin D, Bidny S, Fu S. (2015). Analysis of new designer drugs in post-mortem blood using high-resolution mass spectrometry. J Anal Toxicol 39:163–171.
  • Paul M, Ippisch J, Herrmann C, et al. (2014). Analysis of new designer drugs and common drugs of abuse in urine by a combined targeted and untargeted LC-HR-QTOFMS approach. Anal Bioanal Chem 406:4425–4441.
  • Pawlik E, Plasser G, Mahler H, Daldrup T. (2012). Studies on the phase I metabolism of the new designer drug 3-fluoromethcathinone using rabbit liver slices. Int J Legal Med 126:231–240.
  • Pearson JM, Hargraves TL, Hair LS, et al. (2012). Three fatal intoxications due to methylone. J Anal Toxicol 36:444–451.
  • Pedersen AJ, Petersen TH, Linnet K. (2013a). In vitro metabolism and pharmacokinetic studies on methylone. Drug Metab Dispos 41:1247–1255.
  • Pedersen AJ, Reitzel LA, Johansen SS, Linnet K. (2013b). In vitro metabolism studies on mephedrone and analysis of forensic cases. Drug Test Anal 5:430–438.
  • Penders TM, Gestring RE, Vilensky DA. (2012). Intoxication delirium following use of synthetic cathinone derivatives. Am J Drug Alcohol Abuse 38:616–617.
  • Peters FT, Meyer MR, Fritschi G, Maurer HH. (2005). Studies on the metabolism and toxicological detection of the new designer drug 4’-methyl-alpha-pyrrolidinobutyrophenone (MPBP) in rat urine using gas chromatography-mass spectrometry. J Chromatogr B: Anal Technol Biomed Life Sci 824:81–91.
  • Pichini S, Rotolo MC, Garcia J, et al. (2014). Neonatal withdrawal syndrome after chronic maternal consumption of 4-methylethcathinone. Forensic Sci Int 245C:e33–e35.
  • Pinorini-Godly MT, Sporket F, Schlapfer M, et al. (2010). Intoxication with butylone and phenazepam among young cocaine users. Toxichem. Krimtech 77:226–227.
  • Pozo OJ, Ibanez M, Sancho JV, et al. (2015). Mass spectrometric evaluation of mephedrone in vivo human metabolism: identification of phase I and phase II metabolites, including a novel succinyl conjugate. Drug Metab Dispos 43:248–257.
  • Regester LE, Chmiel JD, Holler JM, et al. (2015). Determination of designer drug cross-reactivity on five commercial immunoassay screening kits. J Anal Toxicol 39:144–151.
  • Rojek S, Klys M, Strona M, et al. (2012). ‘Legal highs‘-toxicity in the clinical and medico-legal aspect as exemplified by suicide with bk-MBDB administration. Forensic Sci Int 222:e1–e6.
  • Saha K, Partilla JS, Lehner KR, et al. (2015). ‘Second-generation’ mephedrone analogs, 4-MEC and 4-MePPP, differentially affect monoamine transporter function. Neuropsychopharmacology 40:1321–1331.
  • Saito T, Namera A, Osawa M, et al. (2013). SPME–GC–MS analysis of α-pyrrolidinovaleorophenone in blood in a fatal poisoning case. Forensic Toxicol 31:328–332.
  • Sauer C, Peters FT, Haas C, et al. (2009). New designer drug alpha-pyrrolidinovalerophenone (PVP): Studies on its metabolism and toxicological detection in rat urine using gas chromatographic/mass spectrometric techniques. J Mass Spectrom 44:952–964.
  • Sauer C, Hoffmann K, Schimmel U, Peters FT. (2011). Acute poisoning involving the pyrrolidinophenone-type designer drug 4'-methyl-alpha-pyrrolidinohexanophenone (MPHP) Forensic Sci Int 208:e20–e25.
  • Schifano F, Albanese A, Fergus S, et al. (2011). Mephedrone (4-methylmethcathinone; 'meow meow'): Chemical, pharmacological and clinical issues. Psychopharmacology (Berl.) 214:593–602.
  • Shima N, Kakehashi H, Matsura S, et al. (2015). Urinary excretion and metabolism of the a-pyrrolidinophenone designer drug 1-phenyl-2-(pyrrolidin-1-yl)octan-1-one (PV9) in humans. Forensic Toxicol 33:279–294.
  • Shima N, Katagi M, Kamata H, et al. (2013). Urinary excretion and metabolism of the newly encountered designer drug 3,4-dimethylmethcathinone in humans. Forensic Toxicol 31:101–112.
  • Shima N, Katagi M, Kamata H, et al. (2014). Metabolism of the newly encountered designer drug α-pyrrolidinovalerophenone in humans: Identification and quantitation of urinary metabolites. Forensic Toxicol 32:59–67.
  • Shintani-Ishida K. (2015). Identification and quantification of 4′-methoxy-α-pyrrolidinobutiophenone (4-MeOPBP) in human plasma and urine using LC–TOF-MS in an autopsy case. Forensic Toxicol 33:348–354.
  • Simmler LD, Buser TA, Donzelli M, et al. (2013). Pharmacological characterization of designer cathinones in vitro. Br J Pharmacol 168:458–470.
  • Simmler LD, Rickli A, Hoener MC, Liechti ME. (2014). Monoamine transporter and receptor interaction profiles of a new series of designer cathinones. Neuropharmacology 79:152–160.
  • Soh YNA, Elliott S. (2013). An investigation of the stability of emerging new psychoactive substances. Drug Test Anal 6:696–704.
  • Sorensen LK. (2011). Determination of cathinones and related ephedrines in forensic whole-blood samples by liquid-chromatography-electrospray tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 879:727–736.
  • 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 (Phila) 49:499–505.
  • Springer D, Fritschi G, Maurer HH. (2003a). Metabolism and toxicological detection of the new designer drug 3’,4’-methylenedioxy-alpha-pyrrolidinopropiophenone studied in urine using gas chromatography-mass spectrometry. J Chromatogr B: Anal Technol Biomed Life Sci 793:377–388.
  • Springer D, Fritschi G, Maurer HH. (2003b). Metabolism of the new designer drug alpha-pyrrolidinopropiophenone (PPP) and the toxicological detection of PPP and 4’-methyl-alpha-pyrrolidinopropiophenone (MPPP) studied in rat urine using gas chromatography-mass spectrometry. J Chromatogr B: Anal Technol Biomed Life Sci 796:253–266.
  • Springer D, Peters FT, Fritschi G, Maurer HH. (2002). Studies on the metabolism and toxicological detection of the new designer drug 4’-methyl-alpha-pyrrolidinopropiophenone in urine using gas chromatography-mass spectrometry. J Chromatogr B: Anal Technol Biomed Life Sci 773:25–33.
  • Springer D, Peters FT, Fritschi G, Maurer HH. (2003c). New designer drug 4’-methyl-alpha-pyrrolidinohexanophenone: studies on its metabolism and toxicological detection in urine using gas chromatography-mass spectrometry. J Chromatogr B: Anal Technol Biomed Life Sci 789:79–91.
  • Springer D, Peters FT, Fritschi G, Maurer HH. (2003d). New designer drug 4’-methyl-alpha-pyrrolidinohexanophenone: studies on its metabolism and toxicological detection in urine using gas chromatography–mass spectrometry. J Chromatogr B: Anal Technol Biomed Life Sci 5:79–91.
  • Springer D, Staack RF, Paul LD, et al. (2003e). Identification of cytochrome P450 enzymes involved in the metabolism of 4’-methoxy-alpha-pyrrolidinopropiophenone (MOPPP), a designer drug, in human liver microsomes. Xenobiotica 33:989–998.
  • Springer D, Staack RF, Paul LD, et al. (2005). Identification of cytochrome P450 enzymes involved in the metabolism of 3’,4’-methylenedioxy-alpha-pyrrolidinopropiophenone (MDPPP), a designer drug, in human liver microsomes. Xenobiotica 35:227–237.
  • Stiles BM, Fish AF, Cook CA, Silva V. (2016). Bath salt-induced psychosis: nursing assessment, diagnosis, treatment, and outcomes. Perspect Psychiatr Care 52:68–78.
  • Stogner JM, Miller BL. (2013). Investigating the 'bath salt' panic: The rarity of synthetic cathinone use among students in the United States. Drug Alcohol Rev 32:545–549.
  • Strano-Rossi S, Cadwallader AB, De La Torre X, Botre F. (2010). Toxicological determination and in vitro metabolism of the designer drug methylenedioxypyrovalerone (MDPV) by gas chromatography/mass spectrometry and liquid chromatography/quadrupole time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 24:2706–2714.
  • Strano-Rossi S, Odoardi S, Fisichella M, et al. (2014). Screening for new psychoactive substances in hair by ultrahigh performance liquid chromatography–electrospray ionization tandem mass spectrometry. J Chromatogr a 1372c:145–156.
  • Swortwood MJ, Hearn WL, Decaprio AP. (2014). Cross-reactivity of designer drugs, including cathinone derivatives, in commercial enzyme-linked immunosorbent assays. Drug Test Anal 6:716–727.
  • Sykutera M, Bloch-Bogusławska E. (2015). A fatal case of 3,4-dimethylmethcathinone poisoning. Prob Forensic Sci 102:138–148.
  • Sykutera M, Cychowska M, Bloch-Boguslawska E. (2015). A fatal case of pentedrone and α-pyrrolidinovalerophenone poisoning. J Anal Toxicol 39:324–329.
  • Tang MH, Ching CK, Lee CY, et al. (2014). Simultaneous detection of 93 conventional and emerging drugs of abuse and their metabolites in urine by UHPLC-MS/MS. J Chromatogr B: Anal Technol Biomed Life Sci 969:272–284.
  • Tekulve K, Alexander A, Tormoehlen L. (2014). Seizures associated with synthetic cathinone exposures in the pediatric population. Pediatr Neurol 51:67–70.
  • Thornton SL, Gerona RR, Tomaszewski CA. (2012a). Psychosis from a bath salt product containing flephedrone and MDPV with serum, urine, and product quantification. J Med Toxicol 8:310–313.
  • Thornton SL, Lo J, Clark RF, et al. (2012b). Simultaneous detection of multiple designer drugs in serum, urine, and CSF in a patient with prolonged psychosis. Clin Toxicol (Phila) 50:1165–1168.
  • Torrance H, Cooper G. (2010). The detection of mephedrone (4-methylmethcathinone) in 4 fatalities in Scotland. Forensic Sci Int 202:e62–e63.
  • Tsujikawa K, Kuwayama K, Kanamori T, et al. (2013). Thermal degradation of alpha-pyrrolidinopentiophenone during injection in gas chromatography/mass spectrometry. Forensic Sci Int 231:296–299.
  • Tsujikawa K, Mikuma T, Kuwayama K, et al. (2012). Degradation pathways of 4-methylmethcathinone in alkaline solution and stability of methcathinone analogs in various pH solutions. Forensic Sci Int 220:103–110.
  • Tyrkko E, Pelander A, Ketola RA, Ojanpera I. (2013). In silico and in vitro metabolism studies support identification of designer drugs in human urine by liquid chromatography/quadrupole-time-of-flight mass spectrometry. Anal Bioanal Chem 405:6697–6709.
  • United Nations Office on Drugs and Crime (UNODC). (2013). World Drug Report 2013. United Nations publication, Vienna, Sales No. E.13.X1.6.
  • United Nations Office on Drugs and Crime (UNODC). (2015). World Drug Report 2015. United Nations Publication, Sales No. E.15.X1.6.
  • 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 38:233–241.
  • US Drug Enforcement Administration. (2013a). Establishment of drug codes for 26 substances. Final rule. Fed Regist 78:664–666.
  • US Drug Enforcement Administration. (2013b). Schedules of controlled substances: Placement of methylone into schedule I. Fed Regist 78:21818–21825.
  • US Drug Enforcement Administration. (2014a). Schedules of controlled substances: Temporary placement of 10 synthetic cathinones into schedule I. Fed Regist 79:12938–12943.
  • US Drug Enforcement Administration. (2014b). Special report: Synthetic cannabinoids and synthetic cathinones reported in NFLIS, 2010–2013. Springfield, VA.
  • US Drug Enforcement Administration. (2015a). National Forensic Laboratory Information System (NFLIS): 2014 annual report. Springfield, VA.
  • US Drug Enforcement Administration. (2015b). National Forensic Laboratory Information System (NFLIS): 2014 midyear report. Springfield, VA.
  • US Drug Enforcement Administration. (2016). Schedules of Controlled Substances: Extension of Temporary Placement of 10 Synthetic Cathinones in Schedule I of the Controlled Substances Act. Fed Regist 81:11429–11431.
  • Usui K, Aramaki T, Hashiyada M, et al. (2014). Quantitative analysis of 3,4-dimethylmethcathinone in blood and urine by liquid chromatography–tandem mass spectrometry in a fatal case. Leg Med (Tokyo) 16:222–226.
  • Vardakou I, Pistos C, Spiliopoulou C. (2011). Drugs for youth via Internet and the example of mephedrone. Toxicol Lett 201:191–195.
  • Wagner KD, Armenta RF, Roth AM, et al. (2014). Use of synthetic cathinones and cannabimimetics among injection drug users in San Diego, California. Drug Alcohol Depend 141:99–106.
  • Wikstrom M, Thelander G, Nystrom I, Kronstrand R. (2010). Two fatal intoxications with the new designer drug methedrone (4-methoxymethcathinone). J Anal Toxicol 34:594–598.
  • Winstock AR, Mitcheson LR, Deluca P, et al. (2011). Mephedrone, new kid for the chop? Addiction 106:154–161.
  • Wood DM, Davies S, Puchnarewicz M, et al. (2010). Recreational use of mephedrone (4-methylmethcathinone, 4-MMC) with associated sympathomimetic toxicity. J Med Toxicol 6:327–330.
  • Wright TH, Cline-Parhamovich K, Lajoie D, et al. (2013). Deaths involving methylenedioxypyrovalerone (MDPV) in Upper East Tennessee. J Forensic Sci 58:1558–1562.
  • Wyman JF, Lavins ES, Engelhart D, et al. (2013). Postmortem tissue distribution of MDPV following lethal intoxication by ‘bath salts‘. J Anal Toxicol 37:182–185.
  • Zaitsu K, Katagi M, Kamata HT, et al. (2009). Determination of the metabolites of the new designer drugs bk-MBDB and bk-MDEA in human urine. Forensic Sci Int 188:131–139.
  • Zaitsu K, Tatsuno M, Sato T, et al. (2011). Recently abused β-keto derivatives of 3,4-methylenedioxyphenylalkylamines: A review of their metabolisms and toxicological analysis. Forensic Toxicol 29:73–84.
  • Zawilska JB, Wojcieszak J. (2013). Designer cathinones-an emerging class of novel recreational drugs. Forensic Sci Int 231:42–53.

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