Sage Journals: Discover world-class research

Abstract

Recently there has been upsurge in reports that illicit seizures of cocaine and heroin have been adulterated with fentanyl. Surface-enhanced Raman spectroscopy (SERS) provides a useful alternative to current screening procedures that permits detection of trace levels of fentanyl in mixtures. Samples are solubilized and allowed to interact with aggregated colloidal nanostars to produce a rapid and sensitive assay. In this study, we present the quantitative determination of fentanyl in heroin and cocaine using SERS, using a point-and-shoot handheld Raman system. Our protocol is optimized to detect pure fentanyl down to 0.20 ± 0.06 ng/mL and can also distinguish pure cocaine and heroin at ng/mL levels. Multiplex analysis of mixtures is enabled by combining SERS detection with principal component analysis and super partial least squares regression discriminate analysis (SPLS-DA), which allow for the determination of fentanyl as low as 0.05% in simulated seized heroin and 0.10% in simulated seized cocaine samples.

Graphical Abstract

Keywords

Fentanyl heroin cocaine surface-enhanced Raman spectroscopy SERS chemometrics super partial least squares regression discriminate analysis SPLS-DA

Get full access to this article

View all access options for this article.

References

U.S. Centers for Disease Control and Prevention (CDC). “Understanding the Epidemic”. https://www.cdc.gov/drugoverdose/epidemic/index.html [accessed April 16 2020].

U.S. Drug Enforcement Administration (DEA). “DEA Issues Nationwide Alert on Fentanyl as Threat to Health and Public Safety”. https://www.dea.gov/press-releases/2015/03/18/dea-issues-nationwide-alert-fentanyl-threat-health-and-public-safety [accessed Feb 11 2020].

Scholl

Seth

Kariisa

Wilson

, et al. “Drug and Opioid-Involved Overdose Deaths—United States, 2013–2017”. Morb. Mortal. Wkly. Rep. 2018; 67(5152): 1419–1427.

Wilson

Kariisa

Seth

Smith

, et al. “Drug and Opioid-Involved Overdose Deaths—United States, 2017–2018”. Morb. Mortal. Wkly. Rep. 2020; 69(11): 290–297.

United Nations Office on Drugs and Crime (UNDOC). “Global Synthetic Drugs Assessment”. https://www.unodc.org/documents/scientific/Global_Synthetic_Drugs_Assessment_2020.pdf [accessed Jun 28 2021].

O’Donnell

J.K.

Gladden

R.M.

Seth

“Trends in Deaths Involving Heroin and Synthetic Opioids Excluding Methadone and Law Enforcement Drug Product Reports by Census Region—United States, 2006–2015”. Morb. Mortal. Wkly. Rep. 2017; 66(34): 897–903.

U.S. Drug Enforcement Administration (DEA). “Cocaine/Fentanyl Combination in Pennsylvania”. 2018. https://www.dea.gov/documents/2018/2018-02/2018-02-01/cocainefentanyl-combination-pennsylvania [accessed Jun 28 2021].

National Institute on Drug Abuse (NIDA). “Fentanyl”. https://www.drugabuse.gov/drugs-abuse/fentanyl [accessed Nov 2 2020].

Tamburro

L.P.

Al-Hadidi

J.H.

Dragovic

L.J.

“Resurgence of Fentanyl as a Drug of Abuse”. J. Forensic Sci. Med. 2016; 2(2): 111–114.

10.

Poklis

“Fentanyl: A Review for Clinical and Analytical Toxicologists”. Clin. Toxicol. 1995; 33(5): 439–447.

11.

Lovrecic

Gabrovec

Carli

, et al. “Non-Medical Use of Novel Synthetic Opioids: A New Challenge to Public Health”. Int. J. Environ. Res. Public Health. 2019; 16(2): 177–198.

12.

LaRue

Twillman

R.K.

Dawson

Whitley

, et al. “Rate of Fentanyl Positivity Among Urine Drug Test Results Positive for Cocaine or Methamphetamine”. JAMA Netw. Open. 2019; 2(4): e192851.

13.

Spencer

M.R.

Warner

Bastian

B.A.

Trinidad

J.P.

, et al. “Drug Overdose Deaths Involving Fentanyl, 2011–2016”. Natl. Vital Stat. Rep. 2019; 68(3): 1–19.

14.

U.S. Drug Enforcement Administration (DEA). “Emerging Threat Report. Third Quarter 2019”. https://cesar.umd.edu/sites/cesar.umd.edu/files/pubs/DEA-Emerging-Threat-Report-2019-Quarter-3.pdf [accessed Jun 28 2021].

15.

U.S. Drug Enforcement Administration (DEA). “21 CFR 1308–Schedules of Controlled Substances: Temporary Placement of Fentanyl-Related Substances in Schedule I”. Fed. Regist. 2018; 83(25): 5188–5192.

16.

U.S. 116th Congress. “Public Law 116-114: Temporary Reauthorization and Study of the Emergency Scheduling of Fentanyl Analogues Act”. Congr. Rec. Washington, DC: U.S. Government Publishing Office, 2020. Vol. 166. https://www.congress.gov/116/plaws/publ114/PLAW-116publ114.pdf [accessed June 28 2021].

17.

Drug Enforcement Administration

U.S.

“85 FR 2015 Temporary Placement of Fentanyl-Related Substances in Schedule I; Correction”. Fed. Regist. 2020; 85(70): 20155–20155.

18.

U.S. Centers for Disease Control and Prevention (CDC). “CDC's Enhanced State Opioid Overdose Surveillance (ESOOS) Program, 32 states and the District of Columbia reporting”. 2019. https://www.cdc.gov/drugoverdose/pdf/data/CDC_ESOOS_April2019_508.pdf [accessed June 28 2021]..

19.

Marinetti

L.J.

Ehlers

B.J.

“A Series of Forensic Toxicology and Drug Seizure Cases Involving Illicit Fentanyl Alone and in Combination with Heroin, Cocaine or Heroin, and Cocaine”. J. Anal. Toxicol. 2014; 38(8): 592–598.

20.

Wang

Huynh

Barhate

Rodrigues

, et al. “Development of a Homogeneous Immunoassay for the Detection of Fentanyl in Urine”. Forensic Sci. Int. 2011; 206(1–3): 127–131.

21.

Sisco

Verkouteren

Staymates

Lawrence

“Rapid Detection of Fentanyl, Fentanyl Analogues, and Opioids for On-Site or Laboratory Based Drug Seizure Screening Using Thermal Desorption DART-MS and Ion Mobility Spectrometry”. Forensic Chem. 2017; 4: 108–115.

22.

Quintana

Ventura

Grifell

Palma

, et al. “The Hidden Web and the Fentanyl Problem: Detection of Ocfentanil as an Adulterant in Heroin”. Int. J. Drug Policy. 2017; 40: 78–83.

23.

Elbardisy

H.M.

Foster

C.W.

Cumba

Antonides

L.H.

, et al. “Analytical Determination of Heroin, Fentanyl and Fentalogues Using High-Performance Liquid Chromatography with Diode Array and Amperometric Detection”. Anal. Methods. 2019; 11(8): 1053–1063.

24.

Tupper

K.W.

McCrae

Garber

Lysyshyn

, et al. “Initial Results of a Drug Checking Pilot Program to Detect Fentanyl Adulteration in a Canadian Setting”. Drug Alcohol Depend. 2018; 190: 242–245.

25.

Barfidokht

Mishra

R.K.

Seenivasan

Liu

, et al. “Wearable Electrochemical Glove-Based Sensor for Rapid and On-Site Detection of Fentanyl”. Sens. Actuators B. 2019; 296: 126422.

26.

Goodchild

S.A.

Hubble

L.J.

Mishra

R.K.

, et al. “Ionic Liquid-Modified Disposable Electrochemical Sensor Strip for Analysis of Fentanyl”. Anal. Chem. 2019; 91(5): 3747–3753.

27.

Guitton

Désage

Alamercery

Dutruch

, et al. “Gas Chromatographic–Mass Spectrometry and Gas Chromatographic–Fourier Transform Infrared Spectroscopy Assay for the Simultaneous Identification of Fentanyl Metabolites”. J. Chromatogr. B: Biomed. Sci. Appl. 1997; 693(1): 59–70.

28.

Leonard

Haddad

Green

Birke

R.L.

, et al. “SERS, Raman, and DFT Analyses of Fentanyl and Carfentanil: Toward Detection of Trace Samples”. J. Raman Spectrosc. 2017; 48(10): 1323–1329.

29.

Haddad

Comanescu

M.A.

Green

Kubic

T.A.

, et al. “Detection and Quantitation of Trace Fentanyl in Heroin by Surface-Enhanced Raman Spectroscopy”. Anal. Chem. 2018; 90(21): 12678–12685.

30.

Shende

Farquharson

Brouillette

Smith

, et al. “Quantitative Measurements of Codeine and Fentanyl on a Surface-Enhanced Raman-Active Pad Test”. Molecules. 2019; 24(14): 2578.

31.

Haddad

Green

Lombardi

J.R.

“Detection of Fentanyl in Binary Mixtures with Cocaine by Use of Surface-Enhanced Raman Spectroscopy”. Spectrosc. Lett. 2019; 52(8): 462–473.

32.

Wang

Deriu

Mebel

A.M.

, et al. “Surface-Enhanced Raman Spectroscopy, Raman, and Density Functional Theoretical Analyses of Fentanyl and Six Analogs”. J. Raman Spectrosc. 2019; 50(10): 1405–1415.

33.

R. Aroca. Surface-Enhanced Vibrational Spectroscopy. Chichester, UK: John Wiley and Sons, 2006.

34.

E.C. Le Ru, P. Etchegoin. Principles of Surface-Enhanced Raman Spectroscopy. Amsterdam; Boston: Elsevier, 2009.

35.

C. Deriu, J. Paudyal, V. Bhardwaj, B. McCord. “SERS for the Forensic Toxicological Screening of Drugs”. In: V. Bhardwaj, A.J. McGoron, editors. Surface-Enhanced Raman Spectroscopy: Methods, Analysis, and Research. Hauppauge, New York: Nova Science Publishers, 2019. Chap. 6, Pp. 141–164.

36.

Salemmilani

Moskovits

Meinhart

C.D.

“Microfluidic Analysis of Fentanyl-Laced Heroin Samples by Surface-Enhanced Raman Spectroscopy in a Hydrophobic Medium”. Analyst. 2019; 144(9): 3080–3087.

37.

Wang

Zhu

, et al. “Elucidating Fentanyls Differentiation from Morphines in Chemical and Biological Samples with Surface-Enhanced Raman Spectroscopy”. Electrophoresis. 2019; 40(16–17): 2193–2203.

38.

Pang

Yang

“Review of Surface Enhanced Raman Spectroscopic (SERS) Detection of Synthetic Chemical Pesticides”. TrAC, Trends Anal. Chem. 2016; 85(Part A): 73–85.

39.

Goodacre

Graham

Faulds

“Recent Developments in Quantitative SERS: Moving Towards Absolute Quantification”. TrAC, Trends Anal. Chem. 2018; 102: 359–368.

40.

Subaihi

Trivedi

D.K.

Hollywood

K.A.

Bluett

, et al. “Quantitative Online Liquid Chromatography–Surface-Enhanced Raman Scattering (LC-SERS) of Methotrexate and its Major Metabolites”. Anal. Chem. 2017; 89(12): 6702–6709.

41.

Alharbi

Goodacre

“Detection and Quantification of the Opioid Tramadol in Urine Using Surface Enhanced Raman Scattering”. Analyst. 2015; 140(17): 5965–5970.

42.

Monfared

A.M.T.

Tiwari

V.S.

Trudeau

V.L.

Anis

“Surface-Enhanced Raman Scattering Spectroscopy for the Detection of Glutamate and γ-Aminobutyric Acid in Serum by Partial Least Squares Analysis”. IEEE Photonics J. 2015; 7(3): 3900216.

43.

P. de B. Harrington, N.E. Vieira, J. Espinoza, J.K. Nien, R. Romero, A.L. Yergey. “Analysis of variance--principal component analysis: A soft tool for proteomic discovery”. Anal. Chim. Acta. 2005. 544(1--2): 118--127.

44.

Harrington

P. de B.

Kister

Artaud

Dupuy

“Automated Principal Component-Based Orthogonal Signal Correction Applied to Fused Near Infrared–Mid-Infrared Spectra of French Olive Oils”. Anal. Chem. 2009; 81: 7160–7169.

45.

Aloglu

A.K.

Harrington

P. de B.

Sahin

Demir

“Prediction of Total Antioxidant Activity of Prunella L. Species by Automatic Partial Least Square Regression Applied to 2-Way Liquid Chromatographic UV Spectral Images”. Talanta. 2016; 161: 503–510.

46.

Kang

M.W.C.

Khan

F.J.

Tan

E.K.M.

, et al. “Optimizing Gold Nanostars as a Colloid-Based Surface-Enhanced Raman Scattering (SERS) Substrate”. J. Opt. 2015; 17(11): 114013.

47.

Vivó-Truyols

Schoenmakers

P.J.

“Automatic Selection of Optimal Savitzky−Golay Smoothing”. Anal. Chem. 2006; 78(13): 4598–4608.

48.

F. Severcan, P.I. Haris. Vibrational Spectroscopy in Diagnosis and Screening. Amsterdam: IOS Press, 2012.

49.

Harrington

P. de B.

“Multiple Versus Single Set Validation of Multivariate Models to Avoid Mistakes”. Crit. Rev. Anal. Chem. 2018; 48(1): 33–46.

50.

Inscore

Shende

Sengupta

Huang

, et al. “Detection of Drugs of Abuse in Saliva by Surface-Enhanced Raman Spectroscopy (SERS)”. Appl. Spectrosc. 2011; 65(9): 1004–1008.

51.

O.H. Drummer, M. Odell. The Forensic Pharmacology of Drugs of Abuse. London: Arnold, 2001.

52.

Pérez-Mañá

Papaseit

Fonseca

Farré

, et al. “Drug Interactions with New Synthetic Opioids”. Front. Pharmacol. 2018; 9: 1145–1162.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.37 MB

Multivariate Analysis Aided Surface-Enhanced Raman Spectroscopy (MVA-SERS) Multiplex Quantitative Detection of Trace Fentanyl in Illicit Drug Mixtures Using a Handheld Raman Spectrometer

Abstract

Keywords

Get full access to this article

References

Supplementary Material