Raman spectroelectrochemistry for fentanyl detection

The field of forensic science is continually advancing as it integrates newer and more reliable analytical technologies. The landscape of illicit drug detection is ever-changing, with yearly shifts increasing the need for effective screening methods. Currently, these screening approaches are the focus of extensive research.

Rapid and dependable detection of legal and illicit drugs is critical for developing suitable analytical protocols, gathering useful information, conducting successful field investigations, and improving safety for laboratory staff, medical professionals, and crime scene investigators.

This article addresses the opioid fentanyl and how Raman spectroelectrochemistry can help with its forensic identification, according to Dr. Colby Ott, the 2022 Metrohm Young Chemist Award (MYCA) winner.

Fentanyl: Wonder drug or public health menace?

Fentanyl is a synthetic opioid that is about 50 times more powerful than heroin and about 100 times more potent than morphine.^1,2

Due to its potency, pharmaceutical fentanyl is used to treat severe pain, such as advanced-stage cancers. However, patients who are prescribed fentanyl must be carefully monitored because it is a leading cause of drug overdoses and fatalities in the United States and other countries.

Illicit fentanyl comes in several forms, including liquid and powder. In addition, it is often mixed with other illegal substances (such as heroin, cocaine, and methamphetamine) and made into pills that resemble prescription drugs or other opioids.

Fentanyl-laced drugs are very harmful, and many people are unaware that they could come into contact with such a potent opioid while taking illicit drugs.

As little as two milligrams of fentanyl can be lethal, with the risk varying based on an individual's body size, tolerance, and past usage. This minuscule amount significantly heightens the danger of overdose.

Recently, the US Drug Enforcement Administration (DEA) discovered counterfeit tablets containing up to 5 milligrams of fentanyl per tablet, which is more than double the deadly amount.

Fentanyl crisis in society: The data

From 1999 to 2022, over 1.1 million people in the US succumbed to drug overdoses.³ Based on data from the 12 months ending in September 2023, it is projected that synthetic opioids like fentanyl are causing over 200 deaths daily.⁴

In 2023, the DEA made record seizures, including 79.5 million fentanyl-laced pills and nearly 12,000 pounds (about 5400 kg) of fentanyl powder.⁵ Additionally, more than 376.7 million lethal doses of fentanyl were confiscated.⁵ Laboratory tests revealed that 70 % of these seized tablets contained lethal fentanyl levels.⁵

Nearly 110,000 people died in the US as a result of drug overdose in 2022 alone.⁶ Fentanyl and other synthetic opioids were responsible for almost 74,000 of these deaths (Figure 1), or nearly 70 % of the total (Figure 2).⁶

When compared to the rate of opioid overdose deaths, including prescription opioids and heroin (Figure 3), it is evident how dangerous fentanyl is and why there is such a high demand for rapid and reliable fentanyl identification.

Figure 1. Synthetic opioid overdose deaths (mostly fentanyl) in the U.S. over the period of 1999–2022 ⁷. Image Credit: Centers for Disease Control

Figure 2. In 2022, fentanyl was responsible for almost 70% of drug overdose deaths in the U.S. ⁷. Image Credit: Centers for Disease Control

Figure 3. Deaths attributed to opioid overdoses in the U.S. over the period of 1999–2022 [7]. It is clear that synthetic opioids (including fentanyl) have become a major threat to public health in the past decade. Image Credit: Centers for Disease Control and Prevention

Challenges for fentanyl detection methods

Fentanyl test strips are a low-cost detection technique that can assist in the prevention of overdoses. They are made up of small strips of paper that can identify the presence of fentanyl in a variety of drugs (such as cocaine, methamphetamine, and heroin) and forms (like pills, powder, and injectables).

Fentanyl strips, however, usually produce results in three to five minutes. This delay could mean the difference between life and death.

Even if the test is negative, this does not necessarily suggest that the drugs are safe, as the test strips may not detect more potent fentanyl-like chemicals. In addition, test strips are qualitative rather than quantitative, indicating only the presence or absence of fentanyl.

For these reasons, the development of rapid, simple, sensitive, and selective methods for fentanyl detection is crucial.

Raman spectroelectrochemistry combines the benefits of both electrochemistry and Raman spectroscopy to provide an intriguing alternative technique for detecting fentanyl in various substances.

The surface-enhanced Raman scattering (SERS) phenomenon can be used to increase intensity when metallic objects are electrochemically activated. This phenomenon increases sensitivity and enables the detection of extremely low concentrations of the analyte being studied.

Under the guidance of Dr. Luis E Arroyo, Associate Professor in the Forensic and Investigative Science Department at West Virginia University, Dr. Colby Ott has concentrated his research on the development of innovative methods for screening confiscated drugs. The aim is to provide swift and dependable detection in both laboratory and field settings.

The combination of electrochemistry and surface-enhanced Raman spectroscopy (EC-SERS) offers a low-cost and effective approach for detecting fentanyl and its analogs.

Dr. Ott’s research,^8-10 funded by the National Institute of Justice, was conducted using SPELEC RAMAN. SPELEC RAMAN is a spectro-electrochemical instrument that includes a 785 nm laser, a spectrometer, and a potentiostat.

It is controlled by a single software that produces synchronized optical and electrochemical results. Dr. Ott received the 2022 Young Chemist Award from Metrohm USA for his innovative and impactful work.

Dr. Colby Ott (center) receiving the Metrohm USA Young Chemist Award in 2022. Image Credit: Metrohm Middle East FZC

Forensic identification of fentanyl drugs with spectroelectrochemistry

In the following interview, Dr. Colby Ott discusses how his approach to this research opens up new doors for future applications in clinical settings, Point-of-Care (POC) analyses, and other kinds of forensic analysis.

1. What is the advantage of Raman spectroelectrochemistry over other traditional drug detection methods?

The majority of drug identification methods use complex instruments such as GC-MS and LC-MS/MS, which are costly, time-consuming, and require extensive training and maintenance.

Aside from instrumental methods, chemical color tests are commonly used for screening; however, they can produce false positive and negative results. Spectroscopic processes are often faster and cost-effective, and they provide structural information and identification.

Raman spectroelectrochemistry is a rapid method for improving drug screening in the field. It also has the potential to reach rural areas where access to other instruments is limited because of size or costs.

2. What is the contribution of electrochemistry to Raman spectroscopy for the detection of fentanyl?

The inherent downside to Raman spectroscopy is that the signal intensity is substantially lower than that of other spectroscopic methods. However, when a surface-enhanced Raman spectroscopy (SERS) experiment is utilized, the resultant signals are much stronger, resulting in a powerful tool for identifying fentanyl.

Due to its potency, signal enhancement is required when identifying fentanyl, as it is usually found as a minor component mixed with other adulterants and cutting agents. Electrochemistry provides a quick and easy way to generate an acceptable SERS substrate, fulfilling the need for signal enhancement.

3. What are the advantages of using screen-printed electrodes (SPEs) compared to SERS substrates?

Screen-printed electrodes (SPEs) are widely used in many electrochemical applications because of their small size, reproducibility, and ease of usage.

Silver SPEs are an excellent surface alternative for electrochemically generating silver nanoparticles in situ from the electrode material, enhancing the ease of usage in the field. In addition, the disposable and reproducible nature of SPEs makes them useful in forensic settings.

Dr. Colby Ott using SPELEC RAMAN in combination with SPEs for his research on fentanyl detection. Image Credit: Metrohm Middle East FZC

4. How has a portable and fully integrated instrument (potentiostat, laser, and spectrometer in one box) such as SPELEC RAMAN contributed to the success of your research?

The ease of use of the fully integrated Raman spectrometer and potentiostat has made it possible to set up measurements and experiments on one software platform rather than attempting to communicate between different software and instruments.

More importantly, the small footprint has enabled portable measurements, where we have taken the instrument off-site for measurements.

5. How relevant is the real-time acquisition of optical and electrochemical measurements for this research?

As chemical color tests continue to be scrutinized for their restrained performance in screening confiscated drugs, innovative screening methods have become a focal point in forensic chemistry.

Many existing spectroscopic approaches are unable to identify components at low concentrations, particularly in the presence of large amounts of cutting agents and adulterants.

Our spectro-electrochemical method has allowed for the detection of fentanyl and fentanyl analogs in low concentrations and in the presence of common drugs and diluent compounds, offering a potential screening solution for seized drug materials.

6. What is the potential commercial impact of your work?

This approach can be used in analytical schemes at the front end to inform down-the-line decision-making for confirmatory processes. In addition, the portability of the instrument and the experimental method make it suitable for field testing at border crossings, ports of entry, and crime scenes.

We are currently developing methods that could be beneficial in toxicological contexts, where this affordable and easy approach would be used in rural communities, compliance testing, and drug screening.

Conclusion

Fentanyl, a potent synthetic opioid, poses a major overdose risk. Its rapid and dependable detection is crucial for investigative and safety purposes.

Raman spectroelectrochemistry provides a quicker and more effective solution than existing detection methods, particularly in field settings. Dr. Colby Ott’s research in this area, using portable instrumentation, shows potential for clinical and forensic applications with major commercial impact.

References

1. Opioid Overdose | Drug Overdose | CDC Injury Center. Centers for Disease Control and Prevention. https://www.cdc.gov/ (accessed 2024-03-13).
2. Fentanyl Facts. Centers for Disease Control and Prevention. https://www.cdc.gov/ (accessed 2024-03-13).
3. Drug Overdoses - Data Details. National Safety Council. https://injuryfacts.nsc.org/home-and-community/safety-topics/drugoverdoses/data-details/ (accessed 2024-03-13).
4. Ahmad, F. B.; Cisewski, J. A.; Rossen, L. M.; et al. Provisional Drug Overdose Death Counts. Centers for Disease Control and Prevention. https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm (accessed 2024-03-13).
5. One Pill Can Kill. United States Drug Enforcement Administration. https://www.dea.gov/onepill (accessed 2024-03-13).
6. Weiland, N. US Recorded Nearly 110,000 Overdose Deaths in 2022. The New York Times. May 17, 2023.
7. Are fentanyl overdose deaths rising in the US?. USAFacts. https://usafacts.org/articles/are-fentanyl-overdose-deaths-rising-in-the-us/ (accessed 2024-03-13).
8. Ott, C. E.; Burns, A.; Sisco, E.; et al. Targeted Fentanyl Screening Utilizing Electrochemical Surface-Enhanced Raman Spectroscopy (EC-SERS) Applied to Authentic Seized Drug Casework Samples. Forensic Chemistry 2023, 34, 100492. DOI: 10.1016/j.forc.2023.100492
9. Ott, C. E.; Perez-Estebanez, M.; Hernandez, S.; et al. Forensic Identification of Fentanyl and Its Analogs by Electrochemical-Surface Enhanced Raman Spectroscopy (EC-SERS) for the Screening of Seized Drugs of Abuse. Frontiers in Analytical Science 2022, 2. DOI:10.3389/frans.2022.834820
10. González-Hernández, J.; Ott, C. E.; Arcos-Martínez, M. J.; et al. Rapid Determination of the ‘Legal Highs’ 4-MMC and 4-MEC by Spectroelectrochemistry: Simultaneous Cyclic Voltammetry and In Situ Surface-Enhanced Raman Spectroscopy. Sensors 2021, 22 (1), 295. DOI:10.3390/s22010295

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