DEA Special Testing and Research Laboratory Research Overview

DEA Special Testing and Research Laboratory Research Overview Forensic Science Research Federal Stakeholders Meeting February 2018 Jeffrey H. Comparin Laboratory Director Drug Enforcement Administration Special Testing and Research Laboratory

Mission Lab System – STRL The mission of the Drug Enforcement Administration’s Office of Forensic Sciences is to deliver quality forensic information and services to counter the global drug threat Vision Global Leader in Forensic Science

Special Testing and Research Laboratory Dedicated Research Group • Group Supervisor and Seven GS-14 Senior Research Chemists – Three support existing Special Programs and conduct novel research – Two are technology specific • • NMR IRMS – One is an organic synthetic chemist – One specializes in clandestine laboratories • Academic Backgrounds Vary • ~20 Current Projects – Program support, standalone projects, answer urgent agency questions • Research Activities Funded by Operational and Outside Funding – In 2017, for the first time, a separate budget line item for research • Outcomes – Strategic and tactical results for DEA, policymakers and the counterdrug IC – Scientific manuscripts

Special Testing and Research Laboratory Research Budget • Relevant, pre-competitive fundamental research to drive innovation • Funding is leveraged to provide maximum value to industry, academia, and government

Fentanyl Signature Profiling Program Mission Gather Strategic and Tactical Intelligence Link Seizures Determine Synthetic Route Determine Trafficking Routes Develop “Consolidated Priority Organization Targets” (CPOT) Research Projects • Organic Synthesis • Characterization of Unknown Compounds

Quantitative Determination via NMR Counterfeit oxycodone tablets Solvent=D 2 O Maleic acid=ISTD A=Acetaminophen = 26. 1% C=Caffeine = 3. 2% D=Dipyrone = 17. 4% F=Fentanyl = 1. 3% L=Lactose = 15. 6%

Relatively clean profiles = 87% of samples High purity fentanyl + Adulterants = 12% of samples Fentanyl-related impurities enriched <1% of samples Fentanyl GC-MS Impurity Profiles

Static Headspace-GC-MS ISTD CH 2 Cl 2 (0. 073%) Acetone (0. 301%) trace CH 2 Cl 2 (0. 002%) Me. OAc (0. 006%) Me. OH (0. 195%) Et. OH (0. 009%) Et. OAc (0. 001%) ISTD

Fentanyl Moiety Isotopes Low High Fentanyl δ 15 N δ 13 C -5. 6 -31. 5 6. 2 -26. 4 4 -ANPP δ 15 N δ 13 C -5. 6 -31. 6 6. 2 -26. 3 C 3 H 5 O δ 13 C -32. 0 -18. 7 Avg STDEV 2. 1 2. 4 -28. 5 1. 0 2. 4 -28. 0 1. 2 -24. 6 2. 5 Range 11. 8 5. 1 11. 8 5. 3 13. 3

2 Separate Seizures (Linked) Fentanyl δ 15 N=1. 8 δ 13 C=-28. 5 4 -ANPP 6. 0% Fentanyl 44. 8% Dipyrone 20. 1% Mannitol 24. 0% Lactose 08 -22 -16 IN 2 kg Dipyrone artifacts 08 -14 -16 CA 24 kg N-phenylpropanamide 322 -1 6. 0% Fentanyl 45. 4% Dipyrone 25. 5% Mannitol 22. 8% Lactose Fentanyl Identical solvent profiles: Acetone CH 2 Cl 2 Toluene Mesityl oxide δ 15 N=1. 8 δ 13 C=-28. 5

Acetaminophen Fentanyl δ 13 C=-29. 8 Caffeine δ 13 C=-32. 2 Acetylfentanyl 4 -ANPP Caffeine δ 13 C=-32. 2 Benzylfentanyl (J) 06 -23 -16 1. 2% Fentanyl CA 18. 7% Dipyrone 4. 6 kg 25. 5% Acetaminophen 3. 2% Caffeine 12. 5% Mannitol* Fentanyl δ 13 C=-29. 8 C-24 ISTD 05 -05 -16 1. 2% Fentanyl AZ 17. 4% Dipyrone 5 kg 26. 1% Acetaminophen 3. 2% Caffeine 15. 6% Lactose* Dipyrone Artifact Caffeine 2 Separate Counterfeit Tablet Seizures (Linked)

Samples Examined and Linkages Over 1, 100 illicit fentanyl samples examined 41 Sets of seizure linkages made to date that include: • 73 different cases/seizures • 169 different exhibits • Over 300 kg fentanyl originating from China and Mexico

Cocaine Signature Program Mission Origin Determination by Chemical Analyses Research Projects • • CSP Operation Breakthrough Cocaine IRMS Differentiation of Growing Regions

Cocaine Signature Program History 1980 s Research Began 1998 CSP is online 2000 Nature Publication 2000 Science News Award 2002 Country of Origin 2002 Subregional research began 2014 Classificati on Research Complete 2016 Scientific Reports Publication More than 30 years of research producing over 100 scientific publications in peer-

19 Growing Regions Putumayo Amazonas Chapare San Lucas Antioquia Chocó Santander Apurimac Guaviare Arauca Huallaga Valle de Cauca Vaupés Caquetá Meta Vichada Cauca Nariño Norte de Santander

Authentic Leaf Samples

Isoscapes δ 13 C δ 15 N δ 2 H

Alkaloidscapes Tropacocai ne Trimethoxycoc aine Total Truxillines

Final Solution PLS_1 A Chapare PLS_1 A 01 A CUSCO Valle de Cauca PLS_1 A 01 B 1 Bolivia/Peru Cocaine UHV W-Caqueta PLS_2 A 01 PLS_2 San Lucas PLS_2 A Arauca PLS_2 A 02 NDS(I) PLS_3 A Choco Antioquia PLS_3 A 01 PLS_4 A Vaupes Narino PLS_4 A 01 Santander PLS_5 NDS(II) PLS_5 A 01 Vichada Amazonas PLS_6 E-Caqueta PLS_6 A Guaviare Putumayo PLS_6 A 01 Cauca Colombian Meta

Impacts of Sub-Regional Data Understanding Threats to the US Provide information for cocaine trafficking flows Interagency Assessment of Cocaine Movement Host nation targeting Compare geo-sourced data to official estimates Identify shifts in cultivation and production Eradication Strategies

Sub-Region as Lu c 0 n 2 Sa nd er nt a 2 Sa 5 no w n U nk H V 15 U ar iñ o 20 N o ay 25 tu m 30 Pu D ca 35 a. R N bi om C ol C au Percent US Domestic Samples 40 CY 2016 Sub-Regional Classifications 33 26 18 15 10 1 1

Heroin Signature Program Mission Origin Determination by Chemical Analyses Research Projects • Operation Breakthrough • Heroin Sig II Compounds • Opium and Heroin Processing • Opium and Heroin Synthesis • Opium Signature • Heroin and Opium Origin Determination

Heroin Signature Program Research Monitoring Opium Poppy Cultivation: • Conduct ongoing assessment of illicit and licit opium cultivation • Monitor via opium poppy field surveys and with analysis of hundreds of opium samples • Provides the foundation for Heroin Signature and Opium Signature methodologies

Heroin Signature Program Research Collaborations with Universities through CTTSO funding: • • Heroin geo-sourcing using opium poppy DNA (with Syracuse University). The developed method is getting published in Nature Scientific Reports. Heroin geo-sourcing using Sr isotope ratios and trace elemental analysis (with Florida International University and University of Miami).

Methamphetamine Profiling Program Mission Determine Synthetic Routes Monitor Precursor Chemicals Monitor Reagents and Solvents Track Manufacturing Trends Research Projects • MPP • ICPMS • Synthesis of Phenethylamines and Tryptamines

Percentage of Samples PSE-Based Meth versus P 2 P-Based Meth

New P 2 P-Based Profile from Mexico • MPP has been tracking this chemistry since approximately 2014 • Nitrostyrene (NTS) is the pre-precursor • Other essential chemicals: – Benzaldehyde (BNZ) – Nitroethane (NTE) – Iron Powder (BNZ + NTE NTS P 2 P Meth) Note: Mono-methylamine is needed from P 2 P to Meth.

Special Testing and Research Laboratory Research into specific instrumentation or agency-driven initiatives • • • Instrument Evaluation Liquid Phase Separations Reference Materials Nuclear Magnetic Resonance Spectroscopy Isotope Ratio Mass Spectrometry Organic Synthesis • Opportunities to collaborate?

Research into Field-Deployable Instrumentation Needs: adapt to potential threat facing LEO – Agents require presumptive indications – Colorimetric test kits no longer permitted – Field-deployable instruments needed • Requirements – – Easy-to use Lightweight Short analysis time Discrimination power

Evaluations Sample in bag • Request For Information placed – Raman spectrophotometers – Mass spectrometers Raman • Evaluated for – Intuitive user interface (technical and nontechnical users) – Compatibility with known samples/matrices – User-added spectral library freedom

Research using Liquid Phase Separations • Method Development: Abundance of Porphyroxine in Opium from Heroin Producing Regions by UHPLC-MS/MS • • Porphyroxine is an alkaloid that can be used to differentiate opium samples from diverse cultivars of poppies. Research continues to quantitate trace alkaloids such as laudanosine, codamine, etc. in both opium and heroin samples.

Structural Elucidation Research No available reference materials and no comparable data: • NMR Experimentation (1 D & 2 D) Proton NMR (HNMR) Carbon NMR (CNMR) Correlation Spectroscopy (COSY) Heteronuclear Single Quantum Coherence (HSQC) – Heteronuclear Multiple Bond Correlation (HMBC) – – • MS Interpretation 23 compounds structurally elucidated in 2016 – EI - Fragmentation – Accu-TOF DART – Exact mass & fragmentation • Salt Form, Isomer and other tests as appropriate

SWGDRUG Monographs General Information – IUPAC Name – Synonyms Chemical and Physical Data Qualitative Data – NMR – GC/MS – FTIR ü Sample preparation ü Instrument parameters Additional Resources – Links to other resources – Article citations 250 since 2012

Special Testing and Research Laboratory Ongoing Research Initiatives • • • Research Associate Laboratory Director Partner with Universities and Other Federal Agencies Seek Outside Funding Streams Conduct Internal Review and Modify Project Initiation Protocols Continue to Explore Basic and Applied Research Opportunities

Thank You for Your Attention Jeffrey H. Comparin Laboratory Director Drug Enforcement Administration Special Testing and Research Laboratory 22624 Dulles Summit Court Dulles, VA 20166 jeffrey. h. comparin@usdoj. gov