Forensic Analysis of Illicit Drugs and Trace

Explosives using Ambient Pressure

Ionization Mass Spectrometry

Tim M. Brewer, Christopher Szakal, Matthew Staymates, Ed Sisco, Lenny Demoranville, Thomas Forbes, Eric Windsor, Shin Muramato and Greg Gillen

Material Measurement Laboratory (MML)

Surface and Microanalysis Science Division

National Institute of Standards and Technology

The Science and Technology Directorate of the U.S. Department of Homeland Security sponsored

the production of portions of this work under Interagency Agreement HSHQDC-12-X-00024 and

HSHQDC-11-X-00420 with the National Institute of Standards and Technology

Forensic and Trace Contraband Detection

Ambient Desorption

and Ionization

Specific Chemical

Analysis and Detection

Contraband Materials

-Organic

-Inorganic

-Nuclear

API-MS

Plasma Liquid

Photon Thermal

Goals:

1. Next generation technology

for DHS screening

2. Improved technologies for

high throughput forensic

analysis

3. Standard methods for

evaluation of API sources

API-MS Surface Analysis Methodologies

Under Investigation at NIST • Liquid Based Sources

– Electrospray Ionization (ESI)

– Atmospheric Pressure Chemical Ionization (APCI)

– Desorption Electrospray Ionization (DESI) and (SESI)

– Desorption Electro-Flow Focusing Ionization (DEFFI)

– PaperSpray Ionization (PS)

• Plasma Based Sources

– Atmospheric Pressure Glow Discharge (APGD)

– Low Temperature Plasma (LTP)

• Thermal Based Sources

– Atmospheric Pressure Thermal Desorption Ionization (APTDI)

• Laser Based Sources

– Atmospheric Pressure Matrix-Assisted Laser Desorption Ionization (AP-MALDI)

– Laser Diode Thermal Desorption (LDTD)

Why API-MS

• Fast analysis – high sample throughput

• Multiple sources – maximum flexibility

– High ionization efficiency

– Selectivity and flexibility of gas phase and solution phase chemistries

• Sample requirements minimized (direct analysis of wet/insulating/geometric

samples or swipes, + vacuum-incompatible surfaces, non planar, non

conductive)

– Can analyze solids, liquids and vapors both positive and negative polarities

• Performance of Mass Spectrometers and MS/MS (chemical speciation and

identification)

– No need for chromatographic separation

Liquid: DESI Analysis of Explosives Residues

Szakal, C. and Brewer, T.M., Anal. Chem., 2009, 81, 5257-5266

Liquid: DESI C-4 Spectra

C-4 samples from

Montgomery Country

bomb squad

Explosives-containing portions of C-4 samples obtained with liquid-liquid extraction in acetonitrile

(explosives, polars)

Liquid: DESI Fingerprint analysis

Image of a fingerprint after DESI-MS

analysis

500 µm

0

500000

1000000

1500000

2000000

2500000

3000000

3500000

50 150 250 350 450 550 650 750

Sig

na

l In

ten

sit

y

m/z

Cholesterol

Oleic Acid

Squalene

Positive Ion Scan using DESI-MS

Allows for analysis on metal surfaces

Typical enhancement of 10x but have seen up to 2000x enhancement

Liquid: Nebulizer Assisted DESI

Selected Ion Monitoring vs. Frequency

8.0E+04

1.8E+05

2.8E+05

3.8E+05

4.8E+05

5.8E+05

6.8E+05

7.8E+05

8.8E+05

9.8E+05

1 101 201 301 401 0.0E+00

5.0E+05

1.0E+06

1.5E+06

2.0E+06

2.5E+06

3.0E+06

1 11 21 31 41 51 61 71

TNT m/z 226 Cocaine m/z 304

time

Liquid: Desorption Electro-Flow Focusing

Ionization

Liquid: PaperSpray –Directly from Swipes

≤ 5 mm

300 ng RDX

3000 ng PETN

The Swipe is the Ion Source – Little to no Sample Preparation Required

C4 IR Neg

0.0E+00

1.0E+05

2.0E+05

3.0E+05

4.0E+05

5.0E+05

0 100 200 300 400

m/z

Inte

nsit

y (

a.u

.)

C4 IR Pos

0.0E+00

1.0E+04

2.0E+04

3.0E+04

4.0E+04

5.0E+04

0 100 200 300 400 500

m/s

Inte

nsit

y (

a.u

.)

C4 IL Pos

0.0E+00

1.0E+04

2.0E+04

3.0E+04

4.0E+04

5.0E+04

6.0E+04

0 100 200 300 400 500

m/s

Inte

nsit

y (

a.u

.)

C4 IL Neg

0.0E+00

2.0E+05

4.0E+05

6.0E+05

8.0E+05

1.0E+06

1.2E+06

1.4E+06

0 100 200 300 400

m/z

Inte

nsit

y (

a.u

.)

Plasma: APGD Analysis of C-4 Residues

*

*

* *

* *

* *

*

*

*

*

*

* *

* *

*

*

*

*

*

*

*

* *

Negative

m/z

m/z

m/z

Positive

Positive

Negative

*

* * *

*

RDX - 284, 268, 221, 129, 62, 46

DOS or DCA - 127

PIB – 95, 79, 65

*

* * * *

*

*

RDX – 222, 177,131

DOS – 427, 185

DCA – 371, 241, 113

PIB – 97,83,56

* *

*

*

*

*

* *

*

*

*

Placed visible amount on explosive swipe. Plasma 75W and 1 L/min He and O 0.1 L/min. No liquid

needed for extraction.

Plasma: OTC Pharmaceutical - Aleve

0.0E+00

1.0E+05

2.0E+05

3.0E+05

4.0E+05

5.0E+05

6.0E+05

7.0E+05

0 50 100 150 200 250 300

Inte

nsit

y (a.u

.)

m/z

*Naproxen – 230, 185, 170, 154, 116

*

* M+

*

*

*

NIST EI Database Aleve

Molecular ion Signal at m/z 230

EI “like” fragmentation - NIST EI Database Searchable (>200,000 compounds)

Active Ingredient – Naproxen

MW = 230

APGD-MS spectra of Aleve Pill. Plasma 75W and 1 L/min He and O 0.1 L/min

0.0E+00

8.0E+04

1.6E+05

2.4E+05

3.2E+05

4.0E+05

4.8E+05

5.6E+05

0 100 200 300

Inte

nsit

y (a.u

.)

m/z

Plasma: APGD Analysis of Forensic Compounds

APGD-MS spectra of Musinex DM and Sudafed Pills. Plasma 75W and 1 L/min He and O 0.1 L/min

0.0E+00

5.0E+05

1.0E+06

1.5E+06

2.0E+06

0 100 200 300 400 500

Inte

nsit

y (a.u

.)

m/z

*Pseudoephedrine – 330, 165, 118, 77

* M+

* M+M

*

*

*

*Methamphetamine – 150, 134, 58

* MH+

*

Forensic Compounds Characterized by APGD

OTC pharmaceuticals

Mucinex DM

Aleve

Sudafed

Alka-Selzter Plus Nightime

Ibuprofen

Tylenol

Asprin

Explosives

C-4

RDX

PETN

TNT

NG

HMX

Semtex H

Semtex A

Narcotics

THC

Cocaine

Heroin

MDMA

Methamphetamine

Hydrocodone

Plasma: APGD-MS Analysis of Ecstasy and

Cocaine Mixture

APGD-MS spectra of Ecstasy and Cocaine. Plasma 75W and 1 L/min He fragmentation pattern with O to

extensive.

0.0E+00

8.0E+04

1.6E+05

2.4E+05

3.2E+05

4.0E+05

0 50 100 150 200 250 300 350 400

Inte

nsit

y (a.u

.)

m/z

* [M+H]+- Cocaine

* [M+H]+- Ecstasy

MW = 303 MW = 193

Plasma: Low Temperature Plasma –

Explosive Particles

SEMTEX H SEMTEX A

PETN - 378

RDX - 284

PETN - 378

Discha

rge

Gas Plas

ma MS

Inlet

Plasma: LTP Depth Profiling - PMMA

1 2

3

4 5

500µm 1500µm Crater cross section

PMMA

SiO2/Si

ToF-SIMS analysis spots

5 4 3 2 1

ToF-SIMS analysis spots

SIMS depth profiling can reveal changes in chemistry along the depth of the film

0

10000

20000

30000

40000

50000

0 50 100 150 200

Inte

nsit

y (co

un

ts)

Sputter Time (s)

Spot 4

Spot 3

Spot 2

Spot 1

4 3 2 1

m/z 69

C2H3O2+

Results suggest damage is localized at the

surface, and the extent of damage seems

proportional to plasma exposure. In the

sub-surface region, the intensity is seen to

quickly return to steady state values

Laser: AP Laser Diode Thermal Desorption Mass

Spectrometry (LDTD-MS)

Q1 RDX #21-26 RT: 0.18-0.23 AV: 6 SB: 18 0.01-0.17 NL: 3.62E7T: - p APCI Q1MS [15.070-400.000]

50 100 150 200 250 300 350

m/z

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

75

80

85

90

95

100

Rel

ativ

e Ab

unda

nce

255.15

268.16

283.07

227.08

157.30 336.13

46.08

199.29

291.19

143.2388.91319.19

115.16341.3845.03 87.16

41.88

Rela

tiv

e A

bu

nd

an

ce

100

50

0

m/z 100 200 300

TNT

[M-H]-

[NO2]- m/z 226

[M]-

m/z 227

m/z 46

Q1 amm_nitrate #76-80 RT: 0.28-0.30 AV: 5 SB: 31 0.16-0.27 NL: 1.02E8T: - p APCI Q1MS [15.070-150.000]

20 40 60 80 100 120 140

m/z

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

75

80

85

90

95

100

Rela

tive

Abun

danc

e

61.9

89.1

143.187.0 98.163.945.9 121.3 130.9114.959.0 71.142.031.815.8

Rela

tiv

e A

bu

nd

an

ce

100

50

0

m/z 20 140 60 100

[NO3]-

[NO2]-

m/z 62

m/z 46

Ammonium Nitrate

Laser: Narcotics on Currency with AP-MALDI

Matrix Matrix Heroin

0.5 μL CHCA matrix on US Currency with doped heroin

RDX TNT

Thermal: AP Thermal Desorption Ionization -

Mass Spectrometry (APTDI-MS)

Pseudoephedrine Methamphetamine Thermal wire rapidly heated

without subsequent

ionization technique of both

liquids and solids

How do we evaluate APIMS Systems? - Standard

Test Materials • Flexible – many different compounds

• Rapid

• Large dynamic range in mass

• Quantifiable

• Precise high

• Accuracy approximately 5% depending on

material and the ability to measure starting

material purity

Stability of drop size during ~2 hours of jetting

0.2 %0.1260.5Volume, pL

0.2 %0.1048.7Mass, ng

0.2 %0.1260.5Volume, pL

0.2 %0.1048.7Mass, ng

mean SD RSDmean SD RSD

500 m image field SIMS of single inkjet droplet

of cocaine on silicon

Preliminary Quantification with Inkjet Printing

Plasma: APGD of Cocaine

Liquid: DESI of Cocaine and RDX

y = 4496.7x + 29807 R² = 0.9994

0.00E+00

5.00E+05

1.00E+06

1.50E+06

2.00E+06

2.50E+06

3.00E+06

3.50E+06

4.00E+06

4.50E+06

5.00E+06

0 200 400 600 800 1000 1200

Co

un

ts (a.u

.)

Mass (ng)

y = 78806x + 129902 R² = 0.9992

0.00E+00

2.00E+07

4.00E+07

6.00E+07

8.00E+07

1.00E+08

0 200 400 600 800 1000 1200

Co

un

ts (a.u

.)

Mass (ng)

Cocaine

y = 7899.6x - 743.47 R² = 0.9993

0.00E+00

2.00E+06

4.00E+06

6.00E+06

8.00E+06

1.00E+07

0 200 400 600 800 1000 1200

Co

un

ts (a.u

.)

Mass (ng)

RDX

Useful Yields for APIMS Analysis

SIMS community have used for years, there is also growing interest in APIMS.

But, how sensitive are these method of analysis? How does sensitivity

vary between compounds, ion source type and instrument configurations?

One method for evaluation is to measure the useful yield.

Useful yield = number of molecules detected/molecules in analytical volume.

The useful yield takes into account beam induced damage, ionization probability,

instrument transmission and detector efficiency. It is the best measure of the

analytical sensitivity for a given molecule under a given set of experimental

conditions.

SF5

C60

Useful yields of organic molecules under dynamic SIMS cluster

bombardment, Greg Gillen, Christopher Szakal, Tim M. Brewer,

Surf. Interface Anal. 43, 376. 2011

Useful Yield Calculations

Compound Ion m/z DESI APGD LDTD DEFFI LTP APTDI

Cocaine (M+H)+ 304 7.5x10-8

1.8x10-8 2.5x10-11

TNT (M-H)- 226 6.5x10-8 3.9x10-10

7.7x10-7 3.1x10-12

RDX (M+NO3)-

(M+35Cl)- 284

235

2.5x10-8

3.9x10-7 2.5x10-8 3.2x10-8

3.5x10-7 5.2x10-12

PETN (M+NO3)-

(M+35Cl)- 378

351

6.8x10-8

1.5x10-8 5.9x10-8 2.5x10-9

6.5x10-8

AN (NO3)- 62 1.5x10-10 7.0x10-7

Conclusions

• Develop next generation technologies

– Multi-source approach

– Mixture analysis without chromatographic separation

• Improved technologies for high throughput forensic analysis

– Multi-source approach for API-MS of trace and forensic contraband materials allows for

fast, chemical surface analysis of a wide range of materials on multiple substrates

– Characteristic mass spectra for all molecules studied from multiple sampling media

• Objectively evaluate the API sources by leveraging inkjet printing

– A procedure and test materials have been developed to quantify the difference sources

– A procedure and test materials have been developed measure useful yields of a range of organic compounds

Analysis and mechanisms of cyclotrimethylenetrinitramine ion formation in desorption electrospray ionization.

Szakal C, Brewer TM., Anal Chem. 2009 Jul 1;81(13):5257-66

Flow Visualization Techniques for the Evaluation of Non-Contact Trace Contraband Detectors,

M Staymates, G Gillen and W Smith, ASME, 2010, 203-209,

DESI Source Research -

Schlieren imaging

High speed videography,

3000 frames per second

20° incidence angle 65° incidence angle

Recirculation zone formed from jet entrainment

Work with Prosolia

0.0E+00

2.0E+05

4.0E+05

6.0E+05

8.0E+05

1.0E+06

1.2E+06

1.4E+06

1.6E+06

0 100 200 300 400 500

Inte

nsit

y (a.u

.)

m/z

*Hydrocodone – 301, 270, 242

* *

* MH+

0.0E+00

8.0E+04

1.6E+05

2.4E+05

3.2E+05

4.0E+05

4.8E+05

5.6E+05

0 100 200 300

Inte

nsit

y (a.u

.)

m/z

*Methamphetamine – 150, 134, 58

* MH+

*

*

Plasma: APGD-MS Analysis of Illicit

Drugs

MW = 301

MW = 149

APGD-MS spectra of Hydrocodone and Methamphetamine. Plasma 75W and 1 L/min He and O 0.1 L/min

He Low Temperature Plasma

• 20 KV peak-peak , 20-70 KHZ high frequency power supply

• Automated x, y sample stage – lab view

• Multiple gas flow controller

• Heated gas jet

• Sample rotation stage for 2000 RPM depth profiling

• Integrated optical spectroscopy for beam characterization

Atmospheric identification of active ingredients in over-the-counter pharmaceuticals and drugs of abuse by atmospheric

pressure glow discharge mass spectrometry (APGD-MS)† Tim M. Brewer*, Jennifer R. Verkouteren, 2011.

Dischar

ge

Gas Plasm

a MS

Inlet

http://onlinelibrary.wiley.com/doi/10.1002/rcm.5136/abstract

APDTI-MS - Repeatability

Cocaine Cocaine repeat analysis

APTDI-MS

Pseudoephedrine Methamphetamine

APTDI-MS – solid mixture

APTDI mass spectrum of Tylenol Allergy. a) is m/z 151,

M+H+ for acetaminophen, b) is m/z 167, M+ for

phenylephrine, and c) is m/z 256, M+H+ for

diphenhydramine

APTDI mass spectrum of m/z 151, M+H+ for

acetaminophen