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Increasing Diversity of Chemicals in Synthetic Stimulant and Cathinone Cases
 

Increasing Diversity of Chemicals in Synthetic Stimulant and Cathinone Cases

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Hosted by NMS Labs, Tuesday, November 27, 2012 ...

Hosted by NMS Labs, Tuesday, November 27, 2012

Presented by Dr. Barry K. Logan, PhD, DABFT, NMS Labs National Director of Forensic Services

Dr. Barry Logan, Director of Forensic and Toxicological Services at NMS Labs, presents some of the latest developments in the designer drug arena from the perspective of NMS Labs. What started with “Bath Salts” has evolved into a complex culture of experimentation with “Research Chemicals”. With the changes in the law that took place in the summer of 2012, and some high profile enforcement action, the flagrant public sale of the products has moved under the counter and into the back room. Suppliers are diversifying the range of chemicals that appear in these products however, and an alarming number of deaths and adverse events have been reported. Currently, MDPV, methylone, alpha-PVP, pentedrone, 25-I NBOMe, and the stimulant nutritional compound DMAA are among the most frequently encountered drugs in our toxicology populations. This webinar reviews a comprehensive LC-TOF application for screening for designer stimulants and cathinones, and emerging data on their prevalence and adverse effects.

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  • MBDB N -methyl-1,3-benzodioxolylbutanamine TMA synthesized by David Nichols at Purdue University “Flatliner” psychedelic
  • MBDB N -methyl-1,3-benzodioxolylbutanamine
  • Psychonaut mapping project
  • MBDB N -methyl-1,3-benzodioxolylbutanamine
  • MDMA, MDPV and Methylone, but over 4000 other stimulants!
  • 4-MPPP alpha-pyrrolidinopentiophenone not to be confused with 1-Methyl-4-phenyl-4-propionoxypiperidine ( MPPP ) or Desmethylprodine is an opioid analgesic drug developed in the 1940s by researchers at Hoffmann-La Roche Pentylone, analog of methylone – a methylenedioxy beta keto amphetamine
  • Propio analogs of the pyrovalerones. Simply reducing the carbon chain by 2 units. MDPPP is the propio homolog of MDPV. Have some history as stimulant drugs in Europe in the 1990 ’s present in fake MDMA tablets
  • 4-MPPP alpha-pyrrolidinopentiophenone not to be confused with 1-Methyl-4-phenyl-4-propionoxypiperidine ( MPPP ) or Desmethylprodine is an opioid analgesic drug developed in the 1940s by researchers at Hoffmann-La Roche BTCP benzothiophenylcyclohexylpiperidine
  • These are isomers, indistinguishable by LCTOF based on mass, but can be distinguished by LCMSMS. Compare to MDMA and methedrone which have identical mass and retention time, and have to be distinguished by lcmsms in confirmation.
  • Have some history as stimulant drugs in Europe in the 1990 ’s present in fake MDMA tablets. These do have the entactogenic effects associated with the methylenedioxy derivatives of the ampehtamines
  • BTCP is a PCP-like in structure It acts as a potent and selective dopamine reuptake inhibitor (DRI) and a psychostimulant . [1] [2] Has been used as a label for the doamine transporter due to its tight binding. Methoxetamine is ketamine-like and dissociative It is reported to have similar desirable and unwanted effects to ketamine, although some users have reported that the unwanted effects last longer than for ketamine. [8] Little is known about the potential toxicity of methoxetamine, but people have been hospitalized in the US and UK after using it recreationally. [3] [9] [10] Acute cerebellar toxicity has been documented in three cases of hospital admission due to methoxetamine overdose, lasting for between one and four days after exposure. [10]
  • Shulgin compounds
  • Shulgin compounds
  • When this panel is run additional drugs that would not be found show up uin these patients including Amphetamine/methamphetamine BZE/Cocaine, Mescaline, mCPP/Trazodone, ODMT/Tramadol, Pyrovalerone, Mitragynine, Pentylone
  • And the 6530 QTOF. The QTOF can be operated with the collision cell turned of in straight TOF mode, or in MSMS mode to get accurate mass of the daughter ions for structure elucidation – very useful for novel compound or metabolite elucidation. The instruments are benchtop, footprint with a chimney that houses the flight tube which is the portion of the instrument that makes the mass measurement by measuring transit time from the point of acceleration up the flight tube, and reflection back to the detector.
  • The software also provides ion chromatograms of each of the targeted masses within the selected time window for evaluation of the signal quality, background , and peak shape.
  • 25I-NBOMe (2C-I-NBOMe) is a derivative of the phenethylamine psychedelic 2C-I, discovered in 2003 by Ralf Heim at the Free University of Berlin,[1] and subsequently investigated in more detail by a team at Purdue University led by David Nichols.[2] N-methoxy benzyl
  • Shulgin compounds
  • Shulgin compounds
  • It acts as a potent and selective dopamine reuptake inhibitor (DRI) and a psychostimulant . [1] [2]
  • It acts as a potent and selective dopamine reuptake inhibitor (DRI) and a psychostimulant . [1] [2]
  • It acts as a potent and selective dopamine reuptake inhibitor (DRI) and a psychostimulant . [1] [2]
  • It acts as a potent and selective dopamine reuptake inhibitor (DRI) and a psychostimulant . [1] [2]
  • It acts as a potent and selective dopamine reuptake inhibitor (DRI) and a psychostimulant. [1][2]
  • It acts as a potent and selective dopamine reuptake inhibitor (DRI) and a psychostimulant. [1][2]

Increasing Diversity of Chemicals in Synthetic Stimulant and Cathinone Cases Increasing Diversity of Chemicals in Synthetic Stimulant and Cathinone Cases Presentation Transcript

  • Increasing Diversity of ChemicalsinSynthetic Stimulant andCathinone CasesBarry K Logan, Ph.D.,NMS Labs National Director, Forensic Services
  • Designer Drugs1980’sα-methylfentanyl, MPPP, MDMA,1990’s, early 2000’sPMA, rise of methamphetamine1991 Publication of PiHKAL1997 Publication of TiHKAL“Combat Methamphetamine EpidemicAct of 2005”Growth of the InternetBeginnings of the “Research Chemicals”or “New Psychedelic” Movement.
  • Designer DrugsMid 2000’sNew tools for drug synthesisResearch Chemical Supply Industry2C-B, 2C-E, 2C-T-7AMT, DMT, 5-MeO-DiPT2004 Operation Web TrypKhat, cathinone, methcathinone
  • Designer Drugs2008-2012Benzylpiperazines (6+)BZP, TFMPP, m-CPPSynthetic Cannabinoids (200+)JWH series, AM Series, RCS Seriesβ-Keto amphetamines (30+)Ephedrone, mephedrone, methylone, methedrone…Phenethylamines (2C suite) (15+)2C-B, 2C-E, 2C-I, 2C-B, 2C-T-7,…Pyrrolidophenones (pyrovalerones) (20+)α-PVP, MDPV, PPP,…
  • EMCDDA1999: Established a framework foridentifying and assessing risk fromsynthetic drugs:1999: MBDB1999: 4-TMA (thiomethylamphetamine)2002: GHB2003: PMMA2004: TMA-2 (trimethylamphetamine)2007: 2C-I, 2C-T-2, 2C-T-72009: BZP2011: Mephedrone
  • EMCDDA2012: 4-Methylamphetamine
  • MephedroneIsrael, 2004
  • MephedroneIsrael, 2004France, 2007
  • MephedroneIsrael, 2004France, 2007Internet availability, 2007
  • MephedroneIsrael, 2004France, 2007Australia, 2008UK, 2008Denmark, 2008Finland, 2008Internet availability, 2007
  • MephedroneIsrael, 2004France, 2007Australia, 2008UK, 2008Denmark, 2008Finland, 2008USA, 2009Internet availability, 2007
  • EMCDDA
  • • Following smoking, effects are intense but short lived.• Psychedelic–like changes in visual perception.• Mood and somatic changes• Modified perception of external reality.• Decreased ability to interact with self or surroundingsGonzalez, et al, 2006Salvia Divinorum - Effects
  • SalviaPerron BE, Ahmedani BK, Vaughn MG, Glass JE, Abdon A, Wu LT. Am J Drug Alcohol Abuse.2012 Jan;38(1):108-13.Use of Salvia Divinorum in anationally representative sample.
  • • Active component – Salvinorin A• Other natural products ––Salvinorin C-G, Divinatorins A-E, Salvinicin A-B• Synthetic derivatives are under investigation for treatment ofAlzheimers, Parkinsons, schizophrenia, and stimulantdependence.Vortherms and Roth, 2006; Grundmann et al, 2007Salvia Divinorum
  • LCMS/MS Salvinorin Analysis•LCMS/MS• LOD/LOQ• Salvinorin A and B• LLOQ - 1ng/mL• LLOD - 0.25ng/mL
  • NFLIS 2011January 2011 –December 2011
  • NFLIS 2011(16,17)(23-25)
  • NFLIS 2011****https://www.nflis.deadiversion.usdoj.gov/
  • NMS Labs Criminalistics CaseworkSingle Drug Products e.g.Methylone THUNDA CAT ZOOM 2Plant FoodMDPV Vanilla Skyα-PVP Vanilla Sky OmiseBTCP Blue Triangular PillsIsopentedrone/pentedrone ZZ-1MDMA Methylene Homolog Unknown powderMultiple Drug Products e.g.4-MEC, JWH-073, JWH-200, JWH-018ZX-14-MPPP, α-PVP Unknown powderPentylone, pyrovalerone,benzocaine, caffeineUnknown powderTetrahydropalmitine
  • Pyrrolidinophenone Stimulants Ipyrrolidinophenones < cathinones = beta keto amphetaminesα-PVPα-pyrrolidinopentiophenone(α-pyrrolidinovalerophenone)Pyrovalerone4-methyl-α-pyrrolidinopentiophenoneMDPV3,4-methylenedioxy-α-pyrrolidinopentiophenone
  • Pyrrolidinophenone Stimulants IIpyrrolidinophenones < cathinones = beta keto amphetamines4- MPPP4-Methyl-α-pyrrolidinopropiophenoneMOPPP4-Methoxy-α-pyrrolidinopropiophenoneMDPPP3,4-Methylenedioxy-α-pyrrolidinopropiophenone
  • NMS Labs Criminalistics CaseworkSingle Drug Products e.g.Methylone THUNDA CAT ZOOM 2Plant FoodMDPV Vanilla Skyα-PVP Vanilla Sky OmiseBTCP Blue Triangular PillsIsopentedrone/pentedrone ZZ-1MDMA Methylene Homolog Unknown powderMultiple Drug Products e.g.4-MEC, JWH-073, JWH-200, JWH-018ZX-14-MPPP, α-PVP Unknown powderPentylone, pyrovalerone,benzocaine, caffeineUnknown powder
  • Cathinone Stimulants Icathinones = beta keto amphetaminesMephedrone4-methylmethcathinone(4-MMC)Buphedroneα-methylamino-butyrophenone
  • Cathinone Stimulants IIcathinones < beta keto methylenedioxyamphetaminesMethylone3,4-methylenedioxy-N-methylcathinone(bk-MDMA)Butyloneβ-keto-N-methylbenzodioxolylbutanamine(bk-MBDB)Pentyloneβ-keto-N-methylbenzodioxolylpentanamine(bk-MBPB)
  • PCP and Ketamine DerivativesDrugBTCPBenzothiophenylcyclohexylpiperidineBenocyclidineMethoxetamine2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone
  • Legal Status - Federalhttp://www.gpo.gov/fdsys/pkg/BILLS-112s3187enr/pdf/BILLS-112s3187enr.pdfFood and Drug Administration Safety and Innovation ActS.3187
  • Legal Status - MethyloneFood and Drug Administration Safety and Innovation ActS.3187http://www.gpo.gov/fdsys/pkg/FR-2012-10-18/pdf/2012-25639.pdf
  • NMS Labs Drug Screening CasesDrug CountDMAA 66alpha-PVP 62MDPV 39Methylone 324-MEC 11Buphedrone 10Pentylone 8MBZP 7DMA 7Ethylone 7Butylone 63,4 DMMC 52C-I 41,4 DBZP 325I-NBOMe 3Screen:Basic ExtractionEI/GCMSConfirmation:GCMSLCTOFLCMSMS
  • NMS Labs Drug Screening CasesDrug CountDMAA 66alpha-PVP 62MDPV 39Methylone 324-MEC 11Buphedrone 10Pentylone 8MBZP 7DMA 7Ethylone 7Butylone 63,4 DMMC 52C-I 41,4 DBZP 325I-NBOMe 3Screen:Basic ExtractionEI/GCMSConfirmation:GCMSLCTOFLCMSMS
  • DimethylamylamineDimethylamylamineDimethylamylamineDMAAMethylhexanamineHistorical use as a decongestantIntroduced as a dietary aid after the ban on ephedrine, 2006Sold as JACK3D, and OxyEliteProCurrent status is uncertain
  • DimethylamylamineDimethylamylamineDimethylamylamineDMAAMethylhexanamineHistorical use as a decongestantIntroduced as a dietary aid after the ban on ephedrine, 2006Sold as
  • Designer Stimulant Panel - 8756
  • LCTOF Designer Stimulant ScreenLiquid Chromatography-Time of Flight MassSpectrometry (LCTOF/LCQTOF)• Agilent 1200 HPLC system• Agilent 6230 with Jet Stream Technology• Agilent 6530 QTOF• Mass Hunter Softwarehttp://www.nmslabs.com/about-webinars-Agilent-Designer-Stim-October-2012
  • AnalysisLiquid Chromatography-Time of Flight MassSpectrometry (LCTOF/LCQTOF) - Control
  • NMS Labs Drug Screening CasesDrug CountDMAA 66alpha-PVP 62MDPV 39Methylone 324-MEC 11Buphedrone 10Pentylone 8MBZP 7DMA 7Ethylone 7Butylone 63,4 DMMC 52C-I 41,4 DBZP 325I-NBOMe 3Screen:Basic ExtractionEI/GCMSConfirmation:GCMSLCTOFLCMSMS
  • Currently Scheduled 7/9/2012MephedroneMDPV2C-E2C-D2C-C2C-I2C-T-22C-T-42C-H2C-N2C-PMethylone** Temporary extended schedule to April 201325I-NBOMe
  • Phenethylamine Stimulants IIdimethoxyphenethylamines2C-I2,5-dimethoxy-4-iodophenethylamine2C-H2,5-dimethoxyphenethylamine2C-E2,5-dimethoxy-4-ethylphenethylamine
  • Phenethylamine Stimulants IIIBenzyl methoxy dimethoxyphenethylamines (NBOMe)2C-I2,5-dimethoxy-4-iodophenethylamine25-IN-benzyl-1-methoxy-2,5-dimethoxy-4-iodophenethylamine
  • 2C-I and 25I-NBOMEGoogle Insights for Search November 2012
  • 2C-I and 25I-NBOMEGoogle Insights for Search November 2012
  • Adverse Event ReportsSmith C, Cardile AP, Miller M. Bath salts as a "legal high". Am J Med. 2011Nov;124(11):e7-8.Baron M, Elie M, Elie L. An analysis of legal highs: do they contain what itsays on the tin? Drug Test Anal. 2011 Sep;3(9):576-81.Centers for Disease Control and Prevention (CDC). Emergency department visitsafter use of a drug sold as "bath salts"--Michigan, November 13, 2010-March 31,2011. MMWR Morb Mortal Wkly Rep. 2011 May 20;60(19):624-7.Antonowicz JL, Metzger AK, Ramanujam SL. Paranoid psychosis induced byconsumption of methylenedioxypyrovalerone: two cases. Gen Hosp Psychiatry.2011 Nov-Dec;33(6):640.e5-6.Penders TM, Gestring R. Hallucinatory delirium following use of MDPV: "BathSalts". Gen Hosp Psychiatry. 2011 Sep-Oct;33(5):525-6.
  • Missing DataWiegand TJ, Wax PM, Schwartz T, Finkelstein Y, Gorodetsky R, Brent J; J MedToxicol. 2012 Oct 2.
  • SummaryPhenethylamines 2Cseries (Shulgin)25-NBOMe series(Reim/Nichols)Salvia,DMAA,Tryptamines,BenzylpiperazinesPyrrolidinophenonesPyrovaleroneMDPVα-PVPPyrrolidinophenones IIMPPPMOPPPCathinonesbk amphetaminesMephedronePentedroneCathinonesmethylenedioxybk amphetaminesMethyloneButylonePentyloneBenzofurans,AminoindanesCyclohexylpiperazines
  • Mass Spectral Resources
  • Pyrrolidinophenone Stimulants
  • Pyrrolidinophenone Stimulants
  • Pyrrolidinophenone Stimulants
  • Pyrrolidinophenone Stimulants
  • AAFS Annual Meeting 2013•Barry K. Logan, Ph.D•Insight into Emerging Drugs on the US Market throughSolid Dosage and Biological Monitoring•DeMia Pressley•NFLIS Update on Designer Drug Trends in the US andDEA Guidelines for Controlling Cannabimimetic Agents•Roumen Sedefov, MD•Designer Drug Trends in the European Union - Is theFuture Already Here?•Col. Kabrena Goerringer, PhD•The Inaudible Barking Dog: US Policy Implications of"Legal Highs"Workshop #19 “Developments in Emerging and DesignerDrug Markets 2013”
  • AAFS Annual Meeting 2013•Marilyn Huestis, PhD•Assessment of Testing Approaches for Large ScaleDesigner Drug Testing•Michael Baumann, PhD•Pharmacology of "Bath Salts" and Related DesignerDrugs•Jeffrey Moran, PhD•Elucidation of Metabolic Pathways for EmergingCannabinoid Agonists•Jeri Ropero-Miller, PhD•Designer Drugs - A Killer Among Us•Peter Stout, PhD•On-Line Database Resource for the Identification ofNovel and Emerging Drugs
  • • Alex Maggitti• Sherri Kacinko• Matthew McMullin• Fran Diamond• Donna Papsun• Apisri IeamniramitAcknowledgementswww.nmslabs.com