NMR in Forensic Drug Analysis

Aaron Urbas, Katrice Lippa

National Institute of Standards and Technology

Chemical Sciences Division

Mike Hitchcock

U.S. Postal Inspection Service

National Forensic Laboratory
• Brief Introduction to NMR

• Emerging Synthetic Drugs 

• Spin System Modeling of Proton Spectra

• Translating Proton Spectra Across Magnetic 

Fields

• Benchtop NMR 

• Summary and Future Work

Outline
Observed NMR signal is the

free induction decay (FID) 

Fourier transformation is used to 

obtain the frequency spectrum 

from the time domain FID.

A Bit About NMR
Correlation Table

1H NMR of Cocaine
1H1H COSY : neighboring 1H correlations 

Proton

Proton

Homonuclear Correlations
Proton

Carbon

1H13C HSQC : direct bond chemical shift correlations 

Heteronuclear Correlations
NMR in the Forensic Drug Lab

• NMR Active Nuclei (Spin 1⁄2)

•

1H, 13C, 19F, 31P mainly

• 2D experiments offer a wealth of connectivity information 

• COSY : 1H1H single bond correlations

• TOCSY : 1H1H multi-bond correlations

• HSQC : 1H-X single-bond single bond connectivity

• HMBC, HMQC : 1H-X multi-bond single bond connectivity

There are MANY more methods including variants of these and others.

• Quantification

• Absolute purity determinations of reference materials

• Quantification of many compounds from a single standard

• Powerful screening method for unknowns

• In most cases, if it’s soluble and has a proton you can see it 

Essential Structure Elucidation Tool

Analytical Tool 
Cathinones Opioids

• Synthetic drugs mostly in several structurally 

related families

• Hundreds of new compounds in the last decade

Cannabinoids Phenethylamines

Emerging Synthetic Drugs (ESDs)
Fluoromethcathinone Regioisomers

1H NMR (600 MHz, MeOD)
Proton Couplings & Splitting Patterns

1H Correlation Table

Spitting Patterns

Scalar Coupling Constants

www2.chemistry.msu.edu/faculty/reusch/virttxtjml/spectrpy/nmr/nmr1.htm
Atom Shift (ppm) J (Hz)

1 CH 7.365

J(1-2) 7.5

J(1-4) 0.1

J(1-11) 7.5

J(1-F13) 5.7

2 CH 7.8147

J(2-1) 7.5

J(2-4) 2

J(2-11) 2

J(2-F13) 0.2

4 CH 7.6787

J(4-1) 0.1

J(4-2) 2

J(4-11) 2

J(4-F13) 8.9

6 CH 3.8598 J(6-7) 6.1

7 CH3 1.5791 J(7-6) 6.1

J(7) -12.5

9 NH 4.7

10 CH3 2.3423 J(10) -12.5

11 CH 7.2785

J(11-1) 7.5

J(11-2) 2

J(11-4) 2

J(11-F13) 8.9

Predicted Chemical Shifts & 

3-Fluoromethcathinone (3-FMC) Coupling Constants

-NH typically won’t be observed

in solvents with exchangeable 2H 

Predicting 1H NMR Spectrum
3-FMC Measured vs Predicted (1H, 600 MHz, MeOD)

Measured

Predicted

Water

-NH

Ar-H C-H -CH3
Atom Shift (ppm) J (Hz)

1 CH 7.365

J(1-2) 7.5

J(1-4) 0.1

J(1-11) 7.5

J(1-F13) 5.7

2 CH 7.8147

J(2-1) 7.5

J(2-4) 2

J(2-11) 2

J(2-F13) 0.2

4 CH 7.6787

J(4-1) 0.1

J(4-2) 2

J(4-11) 2

J(4-F13) 8.9

6 CH 3.8598 J(6-7) 6.1

7 CH3 1.5791 J(7-6) 6.1

J(7) -12.5

9 NH 4.7

10 CH3 2.3423 J(10) -12.5

11 CH 7.2785

J(11-1) 7.5

J(11-2) 2

J(11-4) 2

J(11-F13) 8.9

Predicted Chemical Shifts & 

Coupling Constants

Atom Shift (ppm) J (Hz)

1 CH 7.647

J(1-2) 7.796

J(1-4) 0

J(1-11) 8.322

J(1-F13) 5.484

2 CH 7.8997

J(2-1) 7.796

J(2-4) 1.615

J(2-11) 0.908

J(2-F13) 0

4 CH 7.7934

J(4-1) 0

J(4-2) 1.615

J(4-11) 2.647

J(4-F13) 9.382

6 CH 5.1198 J(6-7) 7.25

7 CH3 1.5846 J(7-6) 7.25

J(7) -12.5

9 NH 4.7

10 CH3 2.786 J(10) -12.5

11 CH 7.5046

J(11-1) 8.322

J(11-2) 0.908

J(11-4) 2.647

J(11-F13) 8.445

Fit Chemical Shifts &

Coupling Constants

Fitting Prediction to Observation
Resulting 3-FMC Model After Fit

Measured

Modeled

Similar results obtained for 2-FMC & 4-FMC 
Atom Shift 

(ppm) Atom Shift (ppm) Atom Shift (ppm)

2 CH 7.9026 J(2-5) 0.5 J(18-11) 0.5 J(25'-24') 8

J(5-2) 0.5 J(18-15) 0.5 J(25'-24'') 8

J(5-6) 7.5 J(18-16) 1.5 J(25'-25'') -12.4

J(5-7) 1.5 J(18-17) 7.5 J(25'-26') 4

J(5-8) 0.5 J(22'-22'') -12.4 J(25'-26'') 4

J(6-5) 7.5 J(22'-23') 7.7 J(25'-27) 25.2

J(6-7) 7.5 J(22'-23'') 7.7 J(25''-24') 8

J(6-8) 1.5 J(22''-22') -12.4 J(25''-24'') 8

J(7-5) 1.5 J(22''-23') 7.7 J(25''-25') -12.4

J(7-6) 7.5 J(22''-23'') 7.7 J(25''-26') 4

J(7-8) 7.5 J(23'-22') 7.7 J(25''-26'') 4

J(8-5) 0.5 J(23'-22'') 7.7 J(25''-27) 25.2

J(8-6) 1.5 J(23'-23'') -12.4 J(26'-25') 4

J(8-7) 7.5 J(23'-24') 7.9 J(26'-25'') 4

J(11-12) 7.5 J(23'-24'') 7.9 J(26'-26'') -12.4

J(11-18) 0.5 J(23''-22') 7.7 J(26'-27) 46.4

J(12-11) 7.5 J(23''-22'') 7.7 J(26''-25') 4

J(12-15) 0.5 J(23''-23') -12.4 J(26''-25'') 4

J(15-12) 0.5 J(23''-24') 7.9 J(26''-26') -12.4

J(15-16) 7.5 J(23''-24'') 7.9 J(26''-27) 46.4

J(15-17) 1.5 J(24'-23') 7.9 J(28'-28'') -14.9

J(15-18) 0.5 J(24'-23'') 7.9 J(28'-28''') -14.9

J(16-15) 7.5 J(24'-24'') -12.4 J(28''-28') -14.9

J(16-17) 7.5 J(24'-25') 8 J(28''-28''') -14.9

J(16-18) 1.5 J(24'-25'') 8 J(28'''-28') -14.9

J(17-15) 1.5 J(24''-23') 7.9 J(28'''-28'') -14.9

J(17-16) 7.5 J(24''-23'') 7.9

J(17-18) 7.5 J(24''-24') -12.4

J(24''-25') 8

J(24''-25'') 8

6 CH 7.3548

J (Hz)

5 CH 8.584

7 CH 7.22

8 CH 7.4558

11 CH 7.7937

12 CH 7.4556

15 CH 7.9936

16 CH 7.5243

J (Hz)

18 CH 8.6891

22'' CH2 4.32

23' CH2 1.69

22' CH2 4.32

23'' CH2 1.69

24' CH2 1.31

J (Hz)

25' CH2 1.47

26' CH2 4.07

26'' CH2 4.07

25'' CH2 1.47

28' CH3 2.667

28'' CH3 2.667

28''' CH3 2.667

24'' CH2 1.31

17 CH 7.7431

Something a bit more challenging...

(1-(5-fluoropentyl)-1H-indol-3-yl)(4-

methyl-1-naphthalenyl)-methanone

aka.....

MAM-2201

Predicted Chemical Shifts & 

Coupling Constants
Long Story Short.....Almost

600 MHz

600 MHz

(model)

Side Note: A better fit has since been obtained

1H NMR (600 MHz, CDCl3

)

MAM-2201

JH,F JH,F
Translating Model to Different Field Strengths

600

500

400

300

Field

(MHz)
400 MHz

600 MHz

(model)

1H NMR Spectrum of MAM-2201 @ 400 MHz
Transform 600 MHz Model to 400 MHz

400 MHz

(20°C)

600 MHz

(25°C)

Evaluated

@

400 MHz
Chemical Shifts of Model Adjusted
• 40 – 90 MHz Permanent 

Magnet Systems

• Range from ~ $40K -

$100K

• No cryogens, little 

maintenance

• Easy to Use

• Portable to varying 

extents

• Some 2D spectral 

capabilities

Benchtop NMR
1H Spectrum Survey (42 MHz) 

2C-B

MDPV

Caffeine

Cocaine

Methylone

Heroin

Methamphetamine

Testosterone

Propionate

Water
Fluoromethcathinones (

1H, 62 MHz, MeOD)

Water

Solvent
19F NMR Spectra (~58 MHz)

4-FMC

3-FMC

2-FMC

MAM-2201

AM-2201

MAM-2201

AM-2201
Field Translation..... How Low Can You Go?

600

500

400

300

Field

(MHz)
600 MHz Model Transformed to 62 MHz Water

2-Fluoromethcathinone

-NH

Oops!

62 MHz

600 MHz

Model

Evaluated

@

62 MHz
Water

-NH

600 MHz Model Transformed to 62 MHz

3-Fluoromethcathinone

62 MHz

600 MHz

Model

Evaluated

@

62 MHz
600 MHz Model Transformed to 62 MHz

4-Fluoromethcathinone

62 MHz

600 MHz

Model

Evaluated

@

62 MHz

Water

-NH
600 MHz Model Transformed to 62 MHz

MAM-2201
Summary & Future Work

• Briefly discussed the (well-known) utility of NMR 

as a powerful tool in structure elucidation

• Demonstrated the utility of spin system modeling 

of proton NMR spectra

– Facilitate data comparison between instruments/fields

– Potential for rapid confirmation of chemical ID

• Going Forward

– Build up library of modeled spectra

– Explore mixture analysis at high and low field
Acknowledgements

• Support from the NIST Special Programs Office

• Samples from the DEA Special Testing and 

Research Laboratory

Commercial equipment identified in this presentation is not intended to imply 

recommendation or endorsement by the National Institute of Standards and Technology, 

nor is it intended to imply that the materials or equipment identified are necessarily the 

best available for the purpose."

Disclaimer
Thanks!

Check out our 

poster on drug 

classification of 

NMR spectra.