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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 inSynthetic Stimulant and Cathinone Cases
Barry K Logan, Ph.D., NMS Labs National Director, Forensic Services
Designer Drugs1980’s
-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.
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
Designer Drugs
2008-2012
Benzylpiperazines (6+)
BZP, TFMPP, m-CPP
Synthetic Cannabinoids (200+)
JWH series, AM Series, RCS Series
-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+)
-PVP, MDPV, PPP,…
EMCDDA
1999: Established a framework for identifying and assessing risk from synthetic drugs:1999: MBDB 1999: 4-TMA (thiomethylamphetamine)2002: GHB2003: PMMA2004: TMA-2 (trimethylamphetamine)2007: 2C-I, 2C-T-2, 2C-T-72009: BZP2011: Mephedrone
EMCDDA
2012: 4-Methylamphetamine
Mephedrone
Israel, 2004
Mephedrone
Israel, 2004France, 2007
Mephedrone
Israel, 2004France, 2007
Internet availability, 2007
Mephedrone
Israel, 2004France, 2007
Australia, 2008
UK, 2008
Denmark, 2008
Finland, 2008
Internet availability, 2007
Mephedrone
Israel, 2004France, 2007
Australia, 2008
UK, 2008
Denmark, 2008
Finland, 2008
USA, 2009
Internet 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 surroundings
Gonzalez, et al, 2006
Salvia Divinorum - Effects
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.
• 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
LCMS/MS Salvinorin Analysis
•LCMS/MS• LOD/LOQ
• Salvinorin A and B• LLOQ - 1ng/mL• LLOD - 0.25ng/mL
NFLIS 2011
January 2011 – December 2011
NFLIS 2011
(16,17)
(23-25)
NFLIS 2011
*
**
*https://www.nflis.deadiversion.usdoj.gov/
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
Pyrrolidinophenone Stimulants I
pyrrolidinophenones < cathinones = beta keto amphetamines
α-PVPα-pyrrolidinopentiophenone(α-pyrrolidinovalerophenone)
Pyrovalerone4-methyl-α-pyrrolidinopentiophenone
MDPV3,4-methylenedioxy-α-pyrrolidinopentiophenone
Pyrrolidinophenone Stimulants II
pyrrolidinophenones < cathinones = beta keto amphetamines
4- MPPP4'-Methyl-α-pyrrolidinopropiophenone
MOPPP4'-Methoxy-α-pyrrolidinopropiophenone
MDPPP3',4'-Methylenedioxy-α-pyrrolidinopropiophenone
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
Cathinone Stimulants I
cathinones = beta keto amphetamines
Mephedrone4-methylmethcathinone (4-MMC)
Buphedroneα-methylamino-butyrophenone
Cathinone Stimulants II
cathinones < beta keto methylenedioxyamphetamines
Methylone3,4-methylenedioxy-N-methylcathinone(bk-MDMA)
Butyloneβ-keto-N-methylbenzodioxolylbutanamine(bk-MBDB)
Pentyloneβ-keto-N-methylbenzodioxolylpentanamine(bk-MBPB)
PCP and Ketamine Derivatives
Drug
BTCPBenzothiophenylcyclohexylpiperidineBenocyclidine
Methoxetamine2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone
S
N
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
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
NMS Labs Drug Screening Cases
Drug Count
DMAA 66alpha-PVP 62MDPV 39Methylone 324-MEC 11Buphedrone 10Pentylone 8MBZP 7DMA 7Ethylone 7Butylone 63,4 DMMC 52C-I 41,4 DBZP 3
25I-NBOMe 3
Screen:Basic ExtractionEI/GCMS
Confirmation:GCMSLCTOFLCMSMS
NMS Labs Drug Screening Cases
Drug Count
DMAA 66alpha-PVP 62MDPV 39Methylone 324-MEC 11Buphedrone 10Pentylone 8MBZP 7DMA 7Ethylone 7Butylone 63,4 DMMC 52C-I 41,4 DBZP 3
25I-NBOMe 3
Screen:Basic ExtractionEI/GCMS
Confirmation:GCMSLCTOFLCMSMS
Dimethylamylamine
Dimethylamylamine
DimethylamylamineDMAAMethylhexanamine
Historical use as a decongestantIntroduced as a dietary aid after the ban on ephedrine, 2006Sold as JACK3D, and OxyEliteProCurrent status is uncertain
Dimethylamylamine
Dimethylamylamine
DimethylamylamineDMAAMethylhexanamine
Historical use as a decongestantIntroduced as a dietary aid after the ban on ephedrine, 2006Sold as
Designer Stimulant Panel - 8756
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
Analysis
Liquid Chromatography-Time of Flight Mass Spectrometry (LCTOF/LCQTOF) - Control
NMS Labs Drug Screening Cases
Drug Count
DMAA 66alpha-PVP 62MDPV 39Methylone 324-MEC 11Buphedrone 10Pentylone 8MBZP 7DMA 7Ethylone 7Butylone 63,4 DMMC 52C-I 41,4 DBZP 3
25I-NBOMe 3
Screen:Basic ExtractionEI/GCMS
Confirmation:GCMSLCTOFLCMSMS
Currently Scheduled 7/9/2012
MephedroneMDPV2C-E2C-D2C-C2C-I2C-T-22C-T-42C-H2C-N2C-PMethylone*
* Temporary extended schedule to April 201325I-NBOMe
Phenethylamine Stimulants II
dimethoxyphenethylamines
2C-I2,5-dimethoxy-4-iodophenethylamine
2C-H2,5-dimethoxyphenethylamine
2C-E2,5-dimethoxy-4-ethylphenethylamine
Phenethylamine Stimulants III
Benzyl methoxy dimethoxyphenethylamines (NBOMe)
2C-I2,5-dimethoxy-4-iodophenethylamine
25-IN-benzyl-1-methoxy-2,5-dimethoxy-4-iodophenethylamine
2C-I and 25I-NBOME
Google Insights for Search November 2012
2C-I and 25I-NBOME
Google Insights for Search November 2012
Adverse Event Reports
Smith 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 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 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 Data
Wiegand TJ, Wax PM, Schwartz T, Finkelstein Y, Gorodetsky R, Brent J; J Med Toxicol. 2012 Oct 2.
Summary
Phenethylamines 2C series (Shulgin)
25-NBOMe series(Reim/Nichols)
Sal
via,
D
MA
A,
Try
ptam
ines
, B
enzy
lpip
eraz
ines Pyrrolidinophenones
PyrovaleroneMDPVα-PVP
Pyrrolidinophenones II MPPPMOPPP
Cathinones bk amphetamines
MephedronePentedrone
Cathinones methylenedioxy
bk amphetaminesMethyloneButylonePentylone
Benzofurans,Aminoindanes
Cyclohexylpiperazines
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 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”
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
• Alex Maggitti• Sherri Kacinko• Matthew McMullin• Fran Diamond • Donna Papsun
• Apisri Ieamniramit
Acknowledgements
www.nmslabs.com
