DART-TOF MS Forensic Screening of Fentanyl and

Other Emerging Drugs

Erin Shonsey, PhD

November 7, 2017

P.E.I. Police Photo Shows Just How Little Fentanyl And Carfentanil It Takes To Kill. HuffPost Canada. 5/2/2017.For Forensic Use

Relative Potency Comparison

Non-Pharmaceutical Fentanyls (NPFs)

Designer OpioidsFor Forensic UsePrekupec. Misuse of Novel Synthetic Opioids: A Deadly New Trend. J Addict Med. 2017.

Prekupec. Misuse of Novel Synthetic Opioids: A Deadly New Trend. J Addict Med. 2017. For Forensic Use

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Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep

Drug Chemistry Cases Received

FY 2016 FY 2015 FY 2010 FY 2017

DRUG CHEMISTRY 2017MARIHUANA 42.9%

METHAMPHETAMINE 26.1%

COCAINE 14.5%

NARCOTICS 10.7%

BENZODIAZEPINES 6.5%

SYNTHETIC CANNABINOIDS 4.5%

HEROIN 4.1%

NON CONTROLLED 2%

NEGATIVE 2%

CEASE ANALYSES 0.5%

OTHER 0.4%

BATH SALTS/DESIGNER 0.3%

Emerging Drugs of Abuse

• Recently a vast array of synthetic drugs have flooded the community, bringing with them the challenge of identification to the forensic drug chemistry laboratory

• Two different tests on two separate samples are required for identification, on of which must be GC-MS analysis.

• A second technique with considerable flexibility was required to not only cover the analytes commonly seen but to also keep up with the new drugs being found in casework.

Courtesy of A. Headrick

DART-TOF MS Workflow

DART-TOF MS

• The DART is the first open air, ambient ion source for a mass spectrometer

• When coupled to a time of flight instrument, exactmass measurements can be used in the putative identification of compounds

DART-TOF MS

Continuous flow of an

aqueous solution containing

reference standards allows

for a control in every data

file to ensure proper

instrument conditions

Operating Parameters

DART Parameter Settings:

Parameter Setting

Positive Mode

Gas Heater Temperature 350°C

DART Distance 3.0 cm

Reference Ion

Reference Ion

Negative Control

Reference Ion

Reference Ion

Case Sample

Reference Ion

Reference Ion

Case Sample

Emerging Drugs of Abuse

• The DART TOF MS is a powerful first analysis in unknown drug analysis, however it is important to remember that is a screening technique since only the molecular ion is generated

• Compounds with the same molecular formula cannot be differentiated with this technique

Compound Molecular Formula Exact Mass4-Anilinopiperidine C11H16N2 176.1313485

NPP C13H17NO 203.1310142

Acetyl norfentanyl C13H18N2O 218.1419132

Norfentanyl C14H20N2O 232.1575633

Butyryl norfentanyl C15H22N2O 246.1732133

4-Anilino-1-benzylpiperidine C18H22N2 266.1782987

Furanyl norfentanyl C16H18N2O2 270.1368278

4-ANPP C19H24N2 280.1939488

despropionyl ortho-fluorofentanyl C19H23FN2 298.1845269

Despropionyl para-fluorofentanyl C19H23FN2 298.1845269

Benzyl fentanyl C21H26N2O 322.2045135

Acetyl fentanyl C21H26N2O 322.2045135

U-47700 C16H22Cl2N2O 328.1109188

Thienyl fentanyl C19H24N2OS 328.1609341

Acrylfentanyl C22H26N2O 334.2045135

alpha-methyl acetyl fentanyl C22H28N2O 336.2201635

Fentanyl C22H28N2O 336.2201635

Acetyl fentanyl 4-methylphenethyl analog C22H28N2O 336.2201635

Thiofentanyl C20H26N2OS 342.1765842

β-methyl Fentanyl C23H30N2O 350.2358136

Isobutyryl fentanyl C23H30N2O 350.2358136

(±)-trans-3-methyl fentanyl C23H30N2O 350.2358136

(±)-cis-3-methylfentanyl C23H30N2O 350.2358136

Butyryl fentanyl C23H30N2O 350.2358136

para-methylfentanyl C23H30N2O 350.2358136

para-Fluoroacrylfentanyl C22H25FN2O 352.1950916

methoxyacetyl fentanyl C22H28N2O2 352.2150782

β-hydroxy Fentanyl C22H28N2O2 352.2150782

meta-fluorofentanyl C22H27FN2O 354.2107417

para-Fluorofentanyl C22H27FN2O 354.2107417

ortho-Fluorofentanyl C22H27FN2O 354.2107417

Fentanyls and Related Compounds

Compound Molecular Formula Exact Massα-methyl Thiofentanyl C21H28N2OS 356.1922342

β-hydroxythiofentanyl C20H26N2O2S 358.1714988

(±)-cis-3-methylbutyryl fentanyl C24H32N2O 364.2514637

α-methyl Butyryl fentanyl C24H32N2O 364.2514637

Valeryl fentanyl C24H32N2O 364.2514637

para-methoxyfentanyl C23H30N2O2 366.2307282

4-Fluoroisobutyryl fentanyl C23H29FN2O 368.2263918

meta-Fluorobutyryl fentanyl C23H29FN2O 368.2263918

para-Fluorobutyryl fentanyl C23H29FN2O 368.2263918

ortho-Fluorobutyryl fentanyl C23H29FN2O 368.2263918

Heroin C21H23NO5 369.1576229

para-Chlorofentanyl C22H27ClN2O 370.1811912

Ocfentanil C22H27FN2O2 370.2056563

Furanyl fentanyl C24H26N2O2 374.1994281

Furanyl fentanyl 3-furancarboxamide isomer C24H26N2O2 374.1994281

W15 C19H21ClN2O2S 376.1012263

cyclopentyl fentanyl C25H32N2O 376.2514637

Benzyl carfentanil C23H28N2O3 380.2099928

4-methoxy-butyryl fentanyl C24H32N2O2 380.2463783

para-Chloroisobutyryl fentanyl C23H29ClN2O 384.1968413

W-19 C19H22ClN3O2S 391.1121254

Carfentanil C24H30N2O3 394.2256428

W-18 C19H20ClN3O4S 421.0863045

Benzodioxole fentanyl C27H28N2O3 428.2099928

Fentanyls and Related Compounds

Reference Ion

Reference Ion

Case Sample

8.80 9.00 9.20 9.40 9.60 9.80 10.00 10.20 10.40 10.60 10.80

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Time-->

Abundance

Methoxy acetyl Fentanyl

9.247

7.50 8.00 8.50 9.00 9.5010.0010.5011.0011.5012.0012.5013.0013.50

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Abundance

TIC: HIGH POSITIVE B-HYDROXY FENTANYL.D\data.ms

9.854

β-OH Fentanyl

4 0 6 0 8 0 1 0 0 1 2 0 1 4 0 1 6 0 1 8 0 2 0 0 2 2 0 2 4 0 2 6 0 2 8 0 3 0 0 3 2 0 3 4 0

0

1 0 0 0 0 0

2 0 0 0 0 0

3 0 0 0 0 0

4 0 0 0 0 0

5 0 0 0 0 0

6 0 0 0 0 0

7 0 0 0 0 0

8 0 0 0 0 0

9 0 0 0 0 0

1 0 0 0 0 0 0

1 1 0 0 0 0 0

1 2 0 0 0 0 0

1 3 0 0 0 0 0

1 4 0 0 0 0 0

1 5 0 0 0 0 0

1 6 0 0 0 0 0

1 7 0 0 0 0 0

1 8 0 0 0 0 0

1 9 0 0 0 0 0

2 0 0 0 0 0 0

2 1 0 0 0 0 0

2 2 0 0 0 0 0

2 3 0 0 0 0 0

2 4 0 0 0 0 0

2 5 0 0 0 0 0

2 6 0 0 0 0 0

2 7 0 0 0 0 0

2 8 0 0 0 0 0

2 9 0 0 0 0 0

m / z-->

A b u n d a n c e

S c a n 1 3 4 1 (9 .2 4 7 m in ): H IG H P O S IT IV E M E T H O X Y A C E T Y L FE N T A N Y L .D \ d a ta .m s

2 6 1 .1

1 5 8 .12 1 8 .1

1 0 5 .1

4 5 .1

1 9 0 .11 3 2 .1

7 7 .0

3 5 0 .23 0 7 .12 8 4 .1

Methoxy acetyl Fentanyl

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Abundance

Scan 1447 (9.873 min): HIGH POSITIVE B-HYDROXY FENTANYL.D\data.ms

245.1

146.1

189.193.0

42.1

118.1334.2

68.0

277.1216.1

β-OH Fentanyl

It is important to remember that some of these compounds have

similar EI spectra

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Abundance

Scan 1195 (8.385 min): HIGH POSTIVE FENTANYL.D\data.ms

245.1

146.1

189.1

105.1

42.1 77.0

334.2216.1 279.0

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Scan 1447 (9.873 min): HIGH POSITIVE B-HYDROXY FENTANYL.D\data.ms

245.1

146.1

189.193.0

42.1

118.1334.2

68.0

277.1216.1

β-OH Fentanyl Fentanyl

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Abundance

Scan 1447 (9.873 min): HIGH POSITIVE B-HYDROXY FENTANYL.D\ data.ms

245.1

146.1

189.193.0

42.1334.2

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Abundance

#578: Fentanyl

245.1

146.1

189.1

91.1

42.2

340.9 405.2282.9 509.6451.1 553.8

The reference material spectrum matched Fentanyl with a higher quality score (94) than β-OH fentanyl (89).

5 0 1 0 0 1 5 0 2 0 0 2 5 0 3 0 0 3 5 0 4 0 0 4 5 00

1 0 0 0

2 0 0 0

3 0 0 0

4 0 0 0

5 0 0 0

6 0 0 0

7 0 0 0

8 0 0 0

9 0 0 0

m / z -->

A b u n d a n c e

S c a n 1 4 4 7 (9 .8 7 3 m in ): H IG H P O S IT IV E B -H Y D R O X Y F E N T A N Y L .D \ d a ta .m s2 4 5 .1

1 4 6 .1

1 8 9 .19 3 .0

4 2 .1

3 3 4 .22 7 7 .2

5 0 1 0 0 1 5 0 2 0 0 2 5 0 3 0 0 3 5 0 4 0 0 4 5 00

1 0 0 0

2 0 0 0

3 0 0 0

4 0 0 0

5 0 0 0

6 0 0 0

7 0 0 0

8 0 0 0

9 0 0 0

m / z -->

A b u n d a n c e

# 1 1 3 7 : ß -H y d ro x y fe n ta n y l2 4 5 .2

1 4 6 .0

1 8 9 .1

7 7 .0

4 2 .0

3 3 4 .22 8 1 .0 4 0 5 .11 0 9 .0 4 7 9 .03 6 9 .0

Acetyl FentanylU-47700

CarfentanilDespropionyl Fentanyl

Methoxy acetyl FentanylAcrylfentanyl

FuranylfentanylFluorobutyryl fentalyl

Currently Observed in Casework

A Case Example

Oxycodone Tablet

Oxycodone 30 mg (Vintage Pharmaceuticals)www.identadrug.com

Initial Analysis

The match a poor quality and is not a true match.

Second Analysis

Second Analysis

What’s not on this list?

Second Analysis

Conclusions

• The DART-TOF MS is the required forensic screening technique for any suspected fentanyl analogs

• The DART-TOF MS database is easily updated to keep up with the emergence of new drugs

• Validation must occur prior to reporting any positive results for fentanyl analogs

• Interferent studies are a necessity as many compounds will have either the same molecular weight or similar EI spectra

References

UNODC Global Smart Update Volume 17, March 2017.

Durst, R.B.C.J.A.L.a.H.D., Versatile New Ion Source for Analysis of Materials in

Open Air Under Ambient Conditions. Analytical Chemistry, 2005. 77: p. 2297-

2302.

Steiner RR and Larson RL. Validation of the Direct Analysis in Real Time

Source for Use in Forensic Drug Screening. Journal of Forensic Science. 54

(2009) 617-622.

References

1. Amanda L. A. Mohr, Melissa Friscia, Donna Papsun, Sherri L. Kacinko, David Buzby, Barry K. Logan; Analysis of Novel Synthetic Opioids U-47700, U-50488 and Furanyl Fentanyl by LC–MS/MS in Postmortem Casework. J Anal Toxicol 2016; 40 (9): 709-717.

2. Anders Helander, Matilda Backberg, Olof Beck; Intoxications involving the fentanyl analogs acetylfentanyl, 4-methoxybutyrfentanyl and furanylfentanyl: results from the Swedish STRIDA project. Clinical Toxicology, 2016.

3. Chelsea Fort, Byron Curtis, Clay Nichols, Cheryl Niblo; Acetyl Fentanyl Toxicity: Two Case Reports. J Anal Toxicol 2016; 40 (9): 754-757.

4. Davide Guerrieri, Emma Rapp, Markus Roman, Gunilla Thelander, Robert Kronstrand, Acrylfentanyl: Another new psychoactive drug with fatal consequences, Forensic Science International, Volume 277, 2017, Pages e21-e29.

5. Dina M. Swanson, Laura S. Hair, Selly R. Strauch Rivers, Brianna C. Smyth, Sara C. Brogan, Alexis D. Ventoso, Samantha L. Vaccaro, Julia M. Pearson; Fatalities Involving Carfentanil and Furanyl Fentanyl: Two Case Reports. J Anal Toxicol 2017 1-5.

6. Joji Suzuki, Saria El-Haddad; A review: Fentanyl and non-pharmaceutical fentanyls Drug and Alcohol Dependence, 2017 Volume 171, 107-116.

7. Matthew P. Prekupec, MD, Petere A. Mansky, MD, and Michael H. Baumann, PhD; Misuse of Novel

Synthetic Opioids: A Deadly New Trend. Journal of Addiction Medicine 2017.

8. Randall C. Baselt. Disposition of Toxic Drugs and Chemicals in Man. 2014.

For Forensic Use