THE EXPANDING REACH OF THE DESIGNER DRUG MOVEMENT IN 2011: CHALLENGES FOR FORENSIC TOXICOLOGY & CHEMISTRY

Transcription

1 THE EXPANDING REACH OF THE DESIGNER DRUG MOVEMENT IN 2011: CHALLENGES FOR FORENSIC TOXICOLOGY & CHEMISTRY Barry K Logan PhD, DABFT, National Director Forensic Services, NMS Labs Willow Grove PA

2 History and Context

3 Designer Drugs 1980 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.

4 Designer Drugs 1980 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.

5 Designer Drugs 1980 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.

6 Designer Drugs 1980 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. 1995

7 Designer Drugs 1980 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.

8 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

9 Designer Drugs 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,

10 Legal Status

11 Legal Status Title 21 United States Code (USC) Controlled Substances Act Schedules drugs according to their medical use, liability for addiction, and potential for abuse. Schedule I includes: the following hallucinogenic substances, or which contains any of their salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation.

12 Legal Status Section 812. Schedule I (c) 17 compounds including: 3,4-methylenedioxyamphetamine 3,4-methylenedioxymethamphetamine 5-methoxy-3,4-methylenedioxy amphetamine. 3,4,5-trimethoxy amphetamine Diethyltryptamine Dimethyltryptamine. 4-methyl-2,5- diamethoxyamphetamine.

13 Legal Status Temporary Scheduling 3/1/2011 Synthetic Cannabinoids JWH-018 JWH-073 JWH-200 CP47,497 (C7) CP47,497 (C8) 10/21/2011 Bath Salts MDPV Mephedrone Methylone

14 Legal Status Federal Analog Act (1986) The Federal Analogue Act defines an analog as a substance which is 'substantially similar' to a scheduled substance and has either an effect 'similar to or greater than' a controlled substance or is thought to have such an effect. Mephedrone 21 U.S.C. 813 Methcathinone

15 Analogs? Yes! USA v Washam (2002) 312 F.3d 926, 930 (i) 1,4-Butanediol and GHB are both linear compounds containing four carbons and that there is only one difference between the substances on one side of their molecules, and (ii) that 1,4-B is metabolized into GHB by the body and so produces substantially similar physiological effects.

16 Analogs? No! USA v. Damon S. Forbes et al. (1992) 806 F.Supp. 232 (i) AET is a primary amine while DMT and DET are tertiary amines, (ii) AET cannot be synthesized from either DMT or DET, and (iii) the hallucinogenic or stimulant effects of AET are not substantially similar to the effects of DMT or DET. AET DMT DET

17 Synthetic Cannabinoids Update

18 Syn Canns Behavioral Effects

19 Syn Canns and Lethality

20 Syn Canns and Lethality

21 Syn Canns Prevalence Calls to Poison Control Centers NFLIS, Oct 2011

22 % Positive NMS Labs Blood Positivity Rates JWH-018 JWH-073 JWH-250 JWH US DEA Controls JWH-018, 073, 200 and CP,47,497

23 NMS Blood Positivity Rates August 2011-September 2011 JWH-018 JWH-073 JWH-250 AM-2201 RCS-4 Range (ng/ml) Mean ± SD (ng/ml) 2.98 ± ± ± ± ± 0.64 Median (ng/ml) % Positive JWH-019 JWH-081 JWH-122 JWH-210 RCS-8 % Positive No positives for JWH-200, AM-694 Graf, Kacinko & Logan, SOFT, October, 2011

24 Synn Cann Toxicity

25 Synn Cann Toxicity Young AC, Schwarz E, Medina G, Obafemi A, Feng SY, Kane C, Kleinschmidt K. Cardiotoxicity associated with the synthetic cannabinoid, K9, with laboratory confirmation. Am J Emerg Med Jul 28.

26 Bath Salts Update

27 Bath Salts and Depression

28 Bath Salts Toxicity

29 Bath Salts and Violence

30 Bath Salts and Violence

31 Cathinones/MDPV prevalence Calls to Poison Control Centers NFLIS, Oct 2011

32 Cathinones/MDPV prevalence NFLIS, Oct 2011

33 Mephedrone Toxicity

34 Mephedrone Toxicity

35 Bath Salts Toxicity

36 What to test for?

37 Designer Drug Scope Peters FT, Martinez-Ramirez JA. Analytical toxicology of emerging drugs of abuse. Ther Drug Monit Oct;32(5):532-9.

38 Designer Drug Scope Wohlfarth A, Weinmann W. Bioanalysis of new designer drugs. Bioanalysis May;2(5):

39 2011 Synthetic Cannabinoids JWH-007 JWH-015 JWH-018 JWH-018 methyl hexyl homolog JWH-019 JWH-073 JWH-073 methyl butyl homolog JWH-081 JWH-122 JWH-133 JWH-175 JWH-200 JWH-201 JWH-203 JWH-210 JWH-250 JWH-251 JWH-302 JWH-398 CP 47, 497 (C7) CP 47,497 (C8) CP 55,940 AM-694 AM-1220 AM-1241 AM-2201 AM-2233 RCS-4 RCS-8 WIN 48,098 (Pravadoline) WIN 55,212-2 WIN 55,212-3 CB-25 CB-52 HU-210 HU-211 HU-308 HU-331 JT-7770

40 Priority Analytical Targets Designer Stimulants/Hallucinogens: Federal Schedules: Mephedrone, MDPV, and Methylone State Schedule (PA) 4-Methoxymethcathinone 4-Fluoromethcathinone 3-Fluoromethcathinone 2C-C, 2C-D, 2C-E, 2C-H, 2C-I, 2C-N, 2C-P, 2C-T-2, 2C-T-4

41 Priority Analytical Targets Synthetic Cannabinoids: Federal Schedules: HU-210, -211, JWH-018, -073, -200, CP47,497 (C7), (C8) State Schedule JWH-019, JWH-250 Other JWH-120, -210, AM-2201, -694, RCS-4, - 8, JWH-081, WIN48,098

42 Priority Analytical Targets Others: 2C-B-FLY, 2-Bromo-dragonfly Tryptamines (5-MeO-DALT, 5-MeODiPT, AMT, DMT) Mitragynine (Kratom) Mesembrine/mesembrenol/hordenine (Kanna) Phenazepam Next: Aminoindanes, Benzofurans, Classical Hallucinogens Psilocin LSD Salvinorin A/B Dextromethorphan

43 Designer Drugs/Hallucinogens Criminalistics Panel Comprehensive Stimulants and Hallucinogens Panel, Test (7210LI/S) 2,5-Dimethoxy-4-chloroamphetamine 2,5-dimethoxy-4-iodophenethylamine 2,5-dimethoxy-4-n-propylthiophenethylamine 3, 4-methylenedioxyethamphetamine 3,4-Methylenedioxyamphetamine 3,4-Methylenedioxymethamphetamine 3-Trifluoromethylphenylpiperazine 4-Bromo-2,5-Dimethoxyphenethylamine 4-fluoroamphetamine 4-Fluorocathinone 4-methyl-N-ethylcathinone

44 Designer Drugs/Hallucinogens Criminalistics Panel Comprehensive Stimulants and Hallucinogens Panel, Test (7210LI/S) N-hydroxy-3,4-methylenedioxyamphetamine para-chlorophenylpiperazine Pentylone Phencyclidine Psilocin Salvinorin A Scopolamine THC Thujone

45 Designer Drugs/Hallucinogens Toxicology LCTOF Panel Hallucinogens Screen - Expanded, Test (8755B/SP/U) 2C-B 2C-B FLY 2C-I 2C-T-7 Mephedrone Bromo-DragonFLY BZP TFMPP MDMA MDA MDBD AMT DMT Ketamine LSD Salvinorin B PCP Dextromethorphan Psilocybin Bufotenine Scopolamine Atropine 5-MeO-DiPT

46 Designer Drugs/Hallucinogens Toxicology LCMSMS Panel Mephedrone & MDPV Stimulants Designer Drug Test, (2623B/SP/U) Mephedrone MDPV Methylone (coming soon)

47 Choice of Matrix Cathinones, Phenethylamines, Tryptamines, Pyrovalerones Blood/Urine Parent Compound 10/100ng/mL Salvia Blood/Urine Salvinorin A/B 0.1ng/mL Synthetic Cannabinoids Blood Parent Compound ng/mL Urine Metabolites ng/mL Lack of available reference materials Lack of labeled internal standards requires careful validation.

48 Screening Immunoassay Benzylpiperazines Trazodone, meta-chlorophenylpiperazine (an hallucinogenic drug and trazodone metabolite), and the hallucinogen trifluoromethylphenylpiperazine cross-react with the EMIT II ecstasy immunoassay in urine. Logan BK, et al. J Anal Toxicol Nov;34(9): Development of a Novel Benzylpiperazine ELISA Assay for Urine and Blood. Rodrigues* WC et al. SOFT/TIAFT 2011

49 Analytical Technique Immunoassay Phenethylamines Evaluation of commercial enzyme-linked immunosorbent assays to identify psychedelic phenethylamines. Kerrigan S, et al. J Anal Toxicol. 2011;35(7):

50 Analytical Technique Immunoassay Synthetic Cannabinoids NMS Labs data No cross-reactivity of synthetic cannabinoids or metabolites with Immunalysis Cannabinoids ELISA assay, or EMIT II Cannabinoids assay, at 10,000ng/mL Development of New Polyclonal Antibodies for the Screening of JWH Synthetic Cannabinoids and Metabolites Benchikh, ME et al. SOFT/TIAFT 2011

51 JWH-018/073 Urine ELISA Immunoassay Synthetic Cannabinoids Synthetic Cannabinoid Metabolites Screen, Urine Test (9563U) September 20 th, 2011 NMS Labs releases JWH-018 and JWH- 073 ELISA. Cross reacts with 4-OH-JWH-018, 5-OH-JWH-018, 4-OH- JWH-073, 4-OH-JWH-073 Does not cross react with THC-COOH Cutoff = 5 ng/ml

52 Synthetic Cannabinoids Blood - Synthetic Cannabinoids Synthetic Cannabinoids, Blood (Forensic) Test (9560B) JWH-018 JWH-073 JWH-019 JWH-250 JWH-081 JWH-122 JWH-200 AM-2201 AM-694 RCS-4 RCS-8 RCS-4

53 Synthetic Cannabinoids Urine - Synthetic Cannabinoids Synthetic Cannabinoid Metabolites Screen - Expanded, Urine (Forensic) Test (9562U) JWH-018 N-(4-hydroxypentyl) metabolite JWH-018 N-(5-hydroxypentyl) metabolite JWH-019 N-(5-hydroxyhexyl) metabolite JWH-073 N-(3-hydroxybutyl) metabolite JWH-073 N-(4-hydroxybutyl) metabolite JWH-250 N-(4-hydroxypentyl) metabolite* AM-2201 N-(4-hydroxypentyl) metabolite

54 Analytical Technique GCMS Good candidate for parent compounds Limited sensitivity in full scan Most information for structural discrimination of closely related compounds. Some synthetic cannabinoids and amphetamine compounds require derivatization. CP47,497 (C7) DOM

55 Analytical Technique LCMSMS Superior sensitivity Limited fragmentation Shared transitions for close relatives Requires separation in time/good chromatography OH OH N N O O OH JWH-018 monohydroxy JWH-018 dihydroxy

56 JWH-018 Metabolism NMS Labs, June 2011

57 JWH-018/073 Metabolism

58 Analytical Technique High Resolution/LCTOF Superior sensitivity Molecular formula identification Many pairs of isobaric compounds exist HU-210/HU fluoromethcathinone/4-fluoromethcathinone MDMA/3,4-BDB/p-MeO-MMA, etc JWH-007/JWH-019 JWH-122/180 JWH-049/JWH-182 Hudson et al. J Anal Toxicol Jun;34(5):

59 Summary Rapidly changing market. Regulation always a step behind the market. Analog definitions will be fought out in court. Growing evidence of adverse effects. Violence, paranoia, psychosis, possible cardiotoxicity, and unexplained deaths. Laboratories should update their scope and keep it targeted to most prevalent compounds. LCMSMS/LCTOF are the most versatile techniques for detecting biomarkers. Innovative strategies required for identification of metabolites and acquisition of standards.

60 ACKNOWLEDGEMENTS Staff of NMS Labs Criminalistics Toxicological Services Research and Development Department LC-MS/MS Department QUESTIONS?