increasing diversity of chemicals in synthetic stimulant and cathinone cases

Post on 21-Jan-2015

837 Views

Category:

Health & Medicine

2 Downloads

Preview:

Click to see full reader

DESCRIPTION

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.

TRANSCRIPT

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

top related