Detection and Identification of Illicit Drugs and Cutting Agents in Seized Street Drugs: Benchtop NMR Spectrometer & Databasing Software ACD/Labs User Meeting Susanne D. Riegel, Alexander F. G. Maier, Dimitris Argyropoulos, Marie Lange, Marion Baumgarte Baltimore, MD March 8 th , 2020
NMR Instruments and Field Strength 2 Dalitz, F.; Cudaj, M.; Maiwald, M.; Guthausen, G.; Prog. Nuc. Mag. Reson. Spec. 2012 , 60 , 52
Illegal Drugs • Typically classified by: – Legal Classification – e.g., Schedule I, Class A – Effect – e.g., depressant, stimulant, hallucinogen – Molecular Structure – e.g., cannabinoids, opioids, phenethylamines Amphetamine MDMA Methamphetamine Stimulant Psychedelic, entactogen Stimulant • Designer Drugs – synthetic analog of a legal restricted or prohibited drug devised to avoid drug detection and identification. 3
New Psychoactive Substances* (from 2-phenyethylamine) 4 * Defined by EU 2015/1535 ‘Act to combat the distribution of new psychoactive substance’
Why Benchtop NMR Spectroscopy? Benchtop Nik Wipes IR HPLC High-field NMR NMR ✓ ✓ ✓ ✓ X Sample Prep Easy Easy Tedious Easy Easy ✓ ~ ~ ~ ~ Sample Conc Medium Low-medium Low Low-medium Medium ✓ ✓ ✓ ✓ X Analysis Time <1 min <1 min >15 min <1 min <1 min ✓ ✓ ✓ X X Location On-site On-site Off-site Off-site On-site ✓ ✓ X X X Standards Required Required Required Not Required Not Required ✓ ✓ X X Quantitative X with calibration with calibration w/o calibration w/o calibration Capital Cost $ $ $$ $$$$ $$ Operating $ $ $$ $$$ $ Expenditure 5
Considerations for Mobile Laboratory - Stability – temperature (AC & simple heating block), vibration (soft or hard) - Mounting - Power consumption - Automation - Accuracy/reliability 6
Sample Preparation and 1 H NMR Acquisition S AMPLE P REP : Reference Standards Unknown Search Queries - 60 µmol of sample dissolved in - ~30 mg of an unknown drug sample ~0.6 mL DMSO- d 6 or D 2 O (if insoluble) dissolved/suspended in vials of - Vial capped and agitated until dissolved ~0.6 mL DMSO- d 6 and D 2 O completely. - Vials were capped and agitated for 1 min - Transferred to NMR tube - Liquid phase transferred to NMR tube 1 H NMR D ATA A CQUISITION (performed at LKA): 1D 1 H NMR spectrum at 60 MHz scan delay = 1 s SW = 80 ppm ns = 16 or 64 SW center = 20 ppm time = 1 min or 4 min np = 8192 P RE -P ROCESSING (ACD/Labs Macro for automatic processing): - Zero Fill - Baseline - Phase - solvent detection 7
Database 8
Creating a Macro 9
Creating a Macro 10
Creating a Macro 11
Automated Preprocessing: Apply Macro 12
Automated Preprocessing: Apply Macro 13
Case Study: Unknown Street Drug 1. Sample Prep of Unknown: - Spatula of unknown added to vial of ~0.6 mL D 2 O - Sealed and agitated for 1 min - Liquid phase transferred to NMR tube 2. 1 H NMR Spectra Acquisition 3. Load into ACD/Spectrus - Auto Preprocessing Macro - Peak Search with ACD/Spectrus DB 14
Open Unknown 1 H NMR Spectra into ACD/Labs 15
Search Database 16
Database Search Options 17
Database Search 18
First Database Hits: Cocaine 19
Auto Select Best Hits 20
Database Best Hits 21
Adjust Intensity 22
Optimize Hit 23
Optimize hit for Cocaine 24
Residuals of Best Fit for Unknown & Cocaine Std 25
Optimize Hit for Lactose 26
Manually Change Intensity 27
Manually Change Intensity 28
Manually Change Intensity 29
Visualize Sum Instead of Residuals 30
Sum of Database Components on Unknown 31
Manually Investigate Other Potential Hits CH 3 NH Cl CH 3 N O N 32
Visualize Inspect Benzydiamine HCl CH 3 NH Cl CH 3 N O N 33
Visually Inspect bk-2C-B HCl H 3 C O O NH 3 Cl Br O CH 3 34
Visually Inspect Caffeine 35
Optimize Intensity 36
Horizontal Offset Adjustment 37
Line Broadening Adjustment 38
Optimize Hit 39
Caffeine Optimized 40
Visually Inspect Sorbitol OH OH OH HO OH OH 41
Visually Inspect D-Mannitol 42
Visually Inspect Citric Acid O OH O O HO OH OH 43
Select all Matching Components 44
Inspect Matching Components: Sum 45
Case Study: Cocaine cont. 46
Case Study: Cocaine cont. 47
Report: Street Drug Cocaine HCl Caffeine D-Mannitol Cocaine HCl Lactose 33.33 match 16.67 match 83.33 match 50.00 match Compare with GC-MS analysis: - Cocaine HCl (41.9%) - Caffeine - Lactose - D-mannitol/sorbitol 48
Conclusions and Future Work • Successfully acquired and built database for 150+ illicit drugs and cutting agents Peak pick allowed relatively automatic identification of peaks • Want to develop fingerprinting/similarity structures flags • 49
Thanks and Acknowledgments ACD/Labs Kriminaltechnisches Nanalysis Michel Riese Juan Araneda Institut Terry Chu Christian Vidal Paul Hui Nicole Lehnert Neal Gallagher Adam Paulson Amro Hussein 50
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