Increasing Diversity of Chemicals in Synthetic Stimulant and Cathinone Cases
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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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Increasing Diversity of Chemicals in Synthetic Stimulant and Cathinone Cases
- 1. Increasing Diversity of Chemicals in Synthetic Stimulant and Cathinone Cases Barry K Logan, Ph.D., NMS Labs National Director, Forensic Services
- 2. Designer Drugs 1980’s α-methylfentanyl, MPPP, MDMA, 1990’s, early 2000’s PMA, rise of methamphetamine 1991 Publication of PiHKAL 1997 Publication of TiHKAL “Combat Methamphetamine Epidemic Act of 2005” Growth of the Internet Beginnings of the “Research Chemicals” or “New Psychedelic” Movement.
- 3. Designer Drugs Mid 2000’s New tools for drug synthesis Research Chemical Supply Industry 2C-B, 2C-E, 2C-T-7 AMT, DMT, 5-MeO-DiPT 2004 Operation Web Tryp Khat, cathinone, methcathinone
- 4. Designer Drugs 2008-2012 Benzylpiperazines (6+) BZP, TFMPP, m-CPP Synthetic Cannabinoids (200+) JWH series, AM Series, RCS Series β-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,…
- 5. EMCDDA 1999: Established a framework for identifying and assessing risk from synthetic drugs: 1999: MBDB 1999: 4-TMA (thiomethylamphetamine) 2002: GHB 2003: PMMA 2004: TMA-2 (trimethylamphetamine) 2007: 2C-I, 2C-T-2, 2C-T-7 2009: BZP 2011: Mephedrone
- 9. Mephedrone Israel, 2004France, 2007 Internet availability, 2007
- 10. Mephedrone Israel, 2004France, 2007 Australia, 2008 UK, 2008 Denmark, 2008 Finland, 2008 Internet availability, 2007
- 11. Mephedrone Israel, 2004France, 2007 Australia, 2008 UK, 2008 Denmark, 2008 Finland, 2008 USA, 2009 Internet availability, 2007
- 12. EMCDDA
- 13. • 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 surroundings Gonzalez, et al, 2006 Salvia Divinorum - Effects
- 14. Salvia Perron 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 a nationally representative sample.
- 15. • Active component – Salvinorin A • Other natural products – –Salvinorin C-G, Divinatorins A-E, Salvinicin A-B • Synthetic derivatives are under investigation for treatment of Alzheimers, Parkinsons, schizophrenia, and stimulant dependence. Vortherms and Roth, 2006; Grundmann et al, 2007 Salvia Divinorum
- 16. LCMS/MS Salvinorin Analysis •LCMS/MS • LOD/LOQ • Salvinorin A and B • LLOQ - 1ng/mL • LLOD - 0.25ng/mL
- 17. NFLIS 2011 January 2011 – December 2011
- 20. NMS Labs Criminalistics Casework Single Drug Products e.g. Methylone THUNDA CAT ZOOM 2 Plant Food MDPV Vanilla Sky α-PVP Vanilla Sky Omise BTCP Blue Triangular Pills Isopentedrone/pentedrone ZZ-1 MDMA Methylene Homolog Unknown powder Multiple Drug Products e.g. 4-MEC, JWH-073, JWH- 200, JWH-018 ZX-1 4-MPPP, α-PVP Unknown powder Pentylone, pyrovalerone, benzocaine, caffeine Unknown powder Tetrahydropalmitine
- 21. Pyrrolidinophenone Stimulants I pyrrolidinophenones < cathinones = beta keto amphetamines α-PVP α-pyrrolidinopentiophenone (α-pyrrolidinovalerophenone) Pyrovalerone 4-methyl-α- pyrrolidinopentiophenone MDPV 3,4-methylenedioxy-α- pyrrolidinopentiophenone
- 22. Pyrrolidinophenone Stimulants II pyrrolidinophenones < cathinones = beta keto amphetamines 4- MPPP 4'-Methyl-α- pyrrolidinopropiophenone MOPPP 4'-Methoxy-α- pyrrolidinopropiophenone MDPPP 3',4'-Methylenedioxy-α- pyrrolidinopropiophenone
- 23. NMS Labs Criminalistics Casework Single Drug Products e.g. Methylone THUNDA CAT ZOOM 2 Plant Food MDPV Vanilla Sky α-PVP Vanilla Sky Omise BTCP Blue Triangular Pills Isopentedrone/pentedrone ZZ-1 MDMA Methylene Homolog Unknown powder Multiple Drug Products e.g. 4-MEC, JWH-073, JWH- 200, JWH-018 ZX-1 4-MPPP, α-PVP Unknown powder Pentylone, pyrovalerone, benzocaine, caffeine Unknown powder
- 24. Cathinone Stimulants I cathinones = beta keto amphetamines Mephedrone 4-methylmethcathinone (4-MMC) Buphedrone α-methylamino-butyrophenone
- 25. Cathinone Stimulants II cathinones < beta keto methylenedioxyamphetamines Methylone 3,4-methylenedioxy-N- methylcathinone (bk-MDMA) Butylone β-keto-N- methylbenzodioxolylbutanamine (bk-MBDB) Pentylone β-keto-N- methylbenzodioxolylpentanamine (bk-MBPB)
- 26. PCP and Ketamine Derivatives Drug BTCP Benzothiophenylcyclohexylpiperidine Benocyclidine Methoxetamine 2-(3-methoxyphenyl)-2- (ethylamino)cyclohexanone
- 27. Legal Status - Federal http://www.gpo.gov/fdsys/pkg/BILLS-112s3187enr/pdf/BILLS-112s3187enr.pdf Food and Drug Administration Safety and Innovation Act S.3187
- 28. Legal Status - Methylone Food and Drug Administration Safety and Innovation Act S.3187 http://www.gpo.gov/fdsys/pkg/FR-2012-10-18/pdf/2012-25639.pdf
- 29. NMS Labs Drug Screening Cases Drug Count DMAA 66 alpha-PVP 62 MDPV 39 Methylone 32 4-MEC 11 Buphedrone 10 Pentylone 8 MBZP 7 DMA 7 Ethylone 7 Butylone 6 3,4 DMMC 5 2C-I 4 1,4 DBZP 3 25I-NBOMe 3 Screen: Basic Extraction EI/GCMS Confirmation: GCMS LCTOF LCMSMS
- 30. NMS Labs Drug Screening Cases Drug Count DMAA 66 alpha-PVP 62 MDPV 39 Methylone 32 4-MEC 11 Buphedrone 10 Pentylone 8 MBZP 7 DMA 7 Ethylone 7 Butylone 6 3,4 DMMC 5 2C-I 4 1,4 DBZP 3 25I-NBOMe 3 Screen: Basic Extraction EI/GCMS Confirmation: GCMS LCTOF LCMSMS
- 31. Dimethylamylamine Dimethylamylamine Dimethylamylamine DMAA Methylhexanamine Historical use as a decongestant Introduced as a dietary aid after the ban on ephedrine, 2006 Sold as JACK3D, and OxyElitePro Current status is uncertain
- 32. Dimethylamylamine Dimethylamylamine Dimethylamylamine DMAA Methylhexanamine Historical use as a decongestant Introduced as a dietary aid after the ban on ephedrine, 2006 Sold as
- 33. Designer Stimulant Panel - 8756
- 34. LCTOF Designer Stimulant Screen Liquid Chromatography-Time of Flight Mass Spectrometry (LCTOF/LCQTOF) • Agilent 1200 HPLC system • Agilent 6230 with Jet Stream Technology • Agilent 6530 QTOF • Mass Hunter Software http://www.nmslabs.com/about-webinars-Agilent-Designer-Stim-October-2012
- 35. Analysis Liquid Chromatography-Time of Flight Mass Spectrometry (LCTOF/LCQTOF) - Control
- 36. NMS Labs Drug Screening Cases Drug Count DMAA 66 alpha-PVP 62 MDPV 39 Methylone 32 4-MEC 11 Buphedrone 10 Pentylone 8 MBZP 7 DMA 7 Ethylone 7 Butylone 6 3,4 DMMC 5 2C-I 4 1,4 DBZP 3 25I-NBOMe 3 Screen: Basic Extraction EI/GCMS Confirmation: GCMS LCTOF LCMSMS
- 37. Currently Scheduled 7/9/2012 Mephedrone MDPV 2C-E 2C-D 2C-C 2C-I 2C-T-2 2C-T-4 2C-H 2C-N 2C-P Methylone* * Temporary extended schedule to April 2013 25I-NBOMe
- 39. Phenethylamine Stimulants III Benzyl methoxy dimethoxyphenethylamines (NBOMe) 2C-I 2,5-dimethoxy-4-iodophenethylamine 25-I N-benzyl-1-methoxy-2,5-dimethoxy-4- iodophenethylamine
- 40. 2C-I and 25I-NBOME Google Insights for Search November 2012
- 41. 2C-I and 25I-NBOME Google Insights for Search November 2012
- 42. Adverse Event Reports Smith C, Cardile AP, Miller M. Bath salts as a "legal high". Am J Med. 2011 Nov;124(11):e7-8. Baron M, Elie M, Elie L. An analysis of legal highs: do they contain what it says on the tin? Drug Test Anal. 2011 Sep;3(9):576-81. Centers for Disease Control and Prevention (CDC). Emergency department visits after 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 by consumption 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: "Bath Salts". Gen Hosp Psychiatry. 2011 Sep-Oct;33(5):525-6.
- 43. Missing Data Wiegand TJ, Wax PM, Schwartz T, Finkelstein Y, Gorodetsky R, Brent J; J Med Toxicol. 2012 Oct 2.
- 44. Summary Phenethylamines 2C series (Shulgin) 25-NBOMe series (Reim/Nichols) Salvia,DMAA,Tryptamines,Benzylpiperazines Pyrrolidinophenones Pyrovalerone MDPV α-PVP Pyrrolidinophenones II MPPP MOPPP Cathinones bk amphetamines Mephedrone Pentedrone Cathinones methylenedioxy bk amphetamines Methylone Butylone Pentylone Benzofurans, Aminoindanes Cyclohexylpiperazines
- 50. AAFS Annual Meeting 2013 •Barry K. Logan, Ph.D •Insight into Emerging Drugs on the US Market through Solid Dosage and Biological Monitoring •DeMia Pressley •NFLIS Update on Designer Drug Trends in the US and DEA Guidelines for Controlling Cannabimimetic Agents •Roumen Sedefov, MD •Designer Drug Trends in the European Union - Is the Future Already Here? •Col. Kabrena Goerringer, PhD •The Inaudible Barking Dog: US Policy Implications of "Legal Highs" Workshop #19 “Developments in Emerging and Designer Drug Markets 2013”
- 51. AAFS Annual Meeting 2013 •Marilyn Huestis, PhD •Assessment of Testing Approaches for Large Scale Designer Drug Testing •Michael Baumann, PhD •Pharmacology of "Bath Salts" and Related Designer Drugs •Jeffrey Moran, PhD •Elucidation of Metabolic Pathways for Emerging Cannabinoid Agonists •Jeri Ropero-Miller, PhD •Designer Drugs - A Killer Among Us •Peter Stout, PhD •On-Line Database Resource for the Identification of Novel and Emerging Drugs
- 52. • Alex Maggitti • Sherri Kacinko • Matthew McMullin • Fran Diamond • Donna Papsun • Apisri Ieamniramit Acknowledgements www.nmslabs.com
Editor's Notes
- 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]