DART-TOF MS Forensic Screening of Fentanyl and Other Emerging Drugs. Erin Shonsey, PhD November 7, 2017

Transcription

1 DART-TOF MS Forensic Screening of Fentanyl and Other Emerging Drugs Erin Shonsey, PhD November 7, 2017

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

3 Non-Pharmaceutical Fentanyls (NPFs) Designer Opioids Prekupec. Misuse of Novel Synthetic Opioids: A Deadly New Trend. J Addict Med For Forensic Use

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

5 Drug Chemistry Cases Received Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep FY 2016 FY 2015 FY 2010 FY 2017

6 DRUG CHEMISTRY 2017 MARIHUANA 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%

7 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.

8 DART-TOF MS Workflow Courtesy of A. Headrick

9 The DART is the first open air, ambient ion source for a mass spectrometer When coupled to a time of flight instrument, exact mass measurements can be used in the putative identification of compounds DART-TOF MS

10 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

11 Operating Parameters DART Parameter Settings: Parameter Setting Positive Mode Gas Heater Temperature 350 C DART Distance 3.0 cm

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13 Reference Ion Negative Control Reference Ion

14 Reference Ion Case Sample Reference Ion

15 Reference Ion Case Sample Reference Ion

16 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

17 Fentanyls and Related Compounds Compound Molecular Formula Exact Mass 4-Anilinopiperidine C11H16N NPP C13H17NO Acetyl norfentanyl C13H18N2O Norfentanyl C14H20N2O Butyryl norfentanyl C15H22N2O Anilino-1-benzylpiperidine C18H22N Furanyl norfentanyl C16H18N2O ANPP C19H24N despropionyl ortho-fluorofentanyl C19H23FN Despropionyl para-fluorofentanyl C19H23FN Benzyl fentanyl C21H26N2O Acetyl fentanyl C21H26N2O U C16H22Cl2N2O Thienyl fentanyl C19H24N2OS Acrylfentanyl C22H26N2O alpha-methyl acetyl fentanyl C22H28N2O Fentanyl C22H28N2O Acetyl fentanyl 4-methylphenethyl analog C22H28N2O Thiofentanyl C20H26N2OS β-methyl Fentanyl C23H30N2O Isobutyryl fentanyl C23H30N2O (±)-trans-3-methyl fentanyl C23H30N2O (±)-cis-3-methylfentanyl C23H30N2O Butyryl fentanyl C23H30N2O para-methylfentanyl C23H30N2O para-fluoroacrylfentanyl C22H25FN2O methoxyacetyl fentanyl C22H28N2O β-hydroxy Fentanyl C22H28N2O meta-fluorofentanyl C22H27FN2O para-fluorofentanyl C22H27FN2O ortho-fluorofentanyl C22H27FN2O

18 Fentanyls and Related Compounds Compound Molecular Formula Exact Mass α-methyl Thiofentanyl C21H28N2OS β-hydroxythiofentanyl C20H26N2O2S (±)-cis-3-methylbutyryl fentanyl C24H32N2O α-methyl Butyryl fentanyl C24H32N2O Valeryl fentanyl C24H32N2O para-methoxyfentanyl C23H30N2O Fluoroisobutyryl fentanyl C23H29FN2O meta-fluorobutyryl fentanyl C23H29FN2O para-fluorobutyryl fentanyl C23H29FN2O ortho-fluorobutyryl fentanyl C23H29FN2O Heroin C21H23NO para-chlorofentanyl C22H27ClN2O Ocfentanil C22H27FN2O Furanyl fentanyl C24H26N2O Furanyl fentanyl 3-furancarboxamide isomer C24H26N2O W15 C19H21ClN2O2S cyclopentyl fentanyl C25H32N2O Benzyl carfentanil C23H28N2O methoxy-butyryl fentanyl C24H32N2O para-chloroisobutyryl fentanyl C23H29ClN2O W-19 C19H22ClN3O2S Carfentanil C24H30N2O W-18 C19H20ClN3O4S Benzodioxole fentanyl C27H28N2O

19 Reference Ion Case Sample Reference Ion

20 Methoxy acetyl Fentanyl Abundance Time-->

21 β-oh Fentanyl Abundance TIC: HIGHPOSITIVEB-HYDROXYFENTANYL.D\data.ms Time-->

22 A b u n d a n c e Methoxy acetyl Fentanyl S c a n ( 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 m / z-->

23 β-oh Fentanyl Abundance Scan 1447 (9.873 min): HIGH POSITIVE B-HYDROXY FENTANYL.D\ data.ms m/z-->

24 It is important to remember that some of these compounds have similar EI spectra

25 Abundance β-oh Fentanyl Abundance Fentanyl m/z--> 42.1 Scan 1447 (9.873 min): HIGH POSITIVE B-HYDROXY FENTANYL.D\ data.ms m/z--> Scan 1195 (8.385 min): HIGH POSTIVE FENTANYL.D\ data.ms

26 Abundance The reference material spectrum matched Fentanyl with a higher quality score (94) than β-oh fentanyl (89) m/ z--> Abundance m/ z--> 42.1 Scan 1447 (9.873 min): HIGH POSITIVE B-HYDROXY FENTANYL.D\ data.ms # 578: Fentanyl

27 A b u n d a n c e S c a n ( 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 s m / z --> A b u n d a n c e # : ß -H y d ro x y fe n ta n y l m / z -->

28 Currently Observed in Casework Acetyl Fentanyl U Carfentanil Despropionyl Fentanyl Methoxy acetyl Fentanyl Acrylfentanyl Furanylfentanyl Fluorobutyryl fentalyl

29 A Case Example

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32 Oxycodone Tablet Oxycodone 30 mg (Vintage Pharmaceuticals)

33 Initial Analysis

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

35 Second Analysis

36 Second Analysis What s not on this list?

37 Second Analysis

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44 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

45 References UNODC Global Smart Update Volume 17, March 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, : p 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)

46 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 and Furanyl Fentanyl by LC MS/MS in Postmortem Casework. J Anal Toxicol 2016; 40 (9): Anders Helander, Matilda Backberg, Olof Beck; Intoxications involving the fentanyl analogs acetylfentanyl, 4-methoxybutyrfentanyl and furanylfentanyl: results from the Swedish STRIDA project. Clinical Toxicology, Chelsea Fort, Byron Curtis, Clay Nichols, Cheryl Niblo; Acetyl Fentanyl Toxicity: Two Case Reports. J Anal Toxicol 2016; 40 (9): 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-e 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 Joji Suzuki, Saria El-Haddad; A review: Fentanyl and non-pharmaceutical fentanyls Drug and Alcohol Dependence, 2017 Volume 171, 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 Randall C. Baselt. Disposition of Toxic Drugs and Chemicals in Man For Forensic Use