Improved detection of fentanyl using Raman spectroelectrochemistry

The field of forensic science is continually evolving by incorporating newer and more reliable analytical technologies. When it comes to illicit drugs, the landscape changes rapidly every year, and the demand for adequate screening methods rises. Such screening methods are the topic of much research today. Rapid and reliable identification of legal and illicit drugs is essential to ensure that appropriate analytical protocols are developed, useful information is gathered, field investigations are successful, and safety improvements are made for laboratory staff, healthcare practitioners, and crime scene investigators. This blog article discusses the opioid fentanyl and how research from the 2022 winner of the Metrohm Young Chemist Award (MYCA), Dr. Colby Ott, assists in its forensic identification with Raman spectroelectrochemistry.

Fentanyl: wonder drug or public health menace?

Fentanyl is a synthetic opioid estimated to be 50 times stronger than heroin and 100 times more potent than morphine [1,2]. Due to its strength, pharmaceutical fentanyl is prescribed to treat severe pain, e.g., for advanced-stage cancers. However, patients who are prescribed fentanyl should be monitored closely since it is a major contributor to drug overdoses and deaths in the United States and other countries.

Illicit fentanyl is found in different forms, including liquid and powder. Furthermore, it is commonly mixed with other illegal drugs (e.g., heroin, cocaine, and methamphetamine) and made into pills that resemble prescription opioids or other drugs. Fentanyl-laced drugs are extremely dangerous, and many people are unaware that they may come into contact with such a strong opioid when using street drugs.

Just two milligrams of fentanyl can be lethal depending on factors such as a person’s body size, tolerance, and past usage. Such a small amount makes the risk of overdose extremely high. U.S. Drug Enforcement Administration (DEA) analysis has found counterfeit pills ranging up to 5 mg of fentanyl per tablet—more than twice the lethal dose!

Fentanyl crisis in society: the data

In the period from 1999 to 2022, more than 1.1 million people died in the U.S. due to a drug overdose [3]. It is currently estimated that over 200 people die there every day from overdoses related to synthetic opioids like fentanyl (based on numbers for the 12-month period ending in September 2023) [4]. The DEA seized a record number of fentanyl-laced pills (79.5 million) in 2023 along with almost 12,000 pounds (5400 kg) of fentanyl powder [5]. The amount of fentanyl seized in 2023 by the DEA was equivalent to more than 376.7 million lethal doses [5]. Of the pills seized by the DEA, laboratory testing indicates that 70% contain a lethal dose of fentanyl [5].

Approximately 110,000 people died in the U.S. from drug overdoses in 2022 alone [6]. Nearly 74,000 of these deaths were caused by fentanyl and other synthetic opioids (Figure 1), accounting for almost 70% of the total (Figure 2). When compared to the rate of opioid overdose deaths including prescription opioids and heroin (Figure 3), it becomes quite clear how dangerous fentanyl is and why there is such a great need for fast and accurate fentanyl identification.

Challenges for fentanyl detection methods

Fentanyl test strips are a low-cost detection method used to help prevent overdoses and reduce harm. They consist of small strips of paper that can detect the presence of fentanyl in different kinds of drugs (e.g., cocaine, methamphetamine, heroin, etc.) and forms (e.g., pills, powder, and injectables).

However, fentanyl strips typically require three to five minutes to give results. This delay could be the difference between life or death. Even if the test is negative, this may not indicate «safe» drugs, as the test strips might not detect more potent fentanyl-like chemicals. In addition, test strips are qualitative and not quantitative – only indicating the presence or absence of fentanyl. For these reasons, the development of fast, easy, sensitive, and selective methods for fentanyl is imperative.

Raman spectroelectrochemistry combines the advantages of both electrochemistry and Raman spectroscopy as an interesting alternative technique to determine fentanyl in different substances. The electrochemical activation of metallic structures allows the enhancement of Raman intensity thanks to the surface-enhanced Raman scattering (SERS) effect. This phenomenon improves sensitivity and allows the detection of very low concentrations of the analyte under study.
 

Learn more about the advantages of using SERS in our related blog post.

Raman vs SERS… What’s the Difference?

Forensic identification of fentanyl drugs with spectroelectrochemistry

We took the opportunity to interview Dr. Colby Ott and discuss why his approach to this research opens new doors for future applications in clinical situations, Point-of-Care (POC) analyses, and other types of forensic analysis.

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

«Most methods employed for drug identification utilize sophisticated instrumentations like GC-MS and LC-MS/MS, which are expensive, require a lot of training and maintenance, and are time-consuming. Aside from instrumental methods, screening methods using chemical color tests are common; however, they are prone to false positive and negative results. Spectroscopic methods are generally fast, lower cost to the user, and provide structural information and identification. Raman spectroelectrochemistry is a rapid technique that can improve drug screening in the field and could potentially reach rural settings where access to other instrumentation is more limited due to 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 generally much weaker than other spectroscopic techniques. However, when a surface-enhanced Raman spectroscopy (SERS) experiment is used, the obtained signals are much stronger, and you end up with a powerful resource to identify fentanyl. Signal enhancement is needed in fentanyl cases since this drug is generally found as a minor component mixed with other adulterants and cutting agents as a result of its potency. Therefore, electrochemistry provides a means of generating an acceptable SERS substrate quickly and easily, providing the needed enhancement of signal.»

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

«Screen-printed electrodes (SPEs) are popular in many electrochemical applications due to their small size, reproducibility, and ease of use. Silver SPEs provide a great surface alternative to electrochemically generate the silver nanoparticles in situ from the electrode material itself, increasing the ease of use in the field for having a SERS substrate. In addition, the disposable nature and reproducibility of SPEs are an advantage in forensic settings.»

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 allowed for simple measurement and experiment set-up in one software platform rather than attempting to have different software and instruments communicate. More importantly, the small footprint has allowed for 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 limited performance in screening seized drug materials, novel screening methods have become a focal point in forensic chemistry. Many current spectroscopic methods are incapable of identifying components in low concentrations, especially in the presence of large amounts of cutting agents and adulterants. Our spectroelectrochemical approach has allowed for the identification of fentanyl and fentanyl analogs in low concentrations and in the presence of common drugs and diluent compounds, providing a possible screening solution for seized drug materials.»

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

«This type of method could be employed within analytical schemes at the front-end to inform down-the-line decision-making for confirmatory approaches. Additionally, the portability of the instrument and the experimental approach make this work amenable to field testing and could be used at border crossings, ports of entry, and crime scenes. We are currently working on methods that could be useful in toxicological scenarios, where this affordable and simple method would be used in rural communities, compliance testing, and drug screening.»

Conclusion

Fentanyl, a potent synthetic opioid, poses a significant overdose risk. Its rapid and reliable identification is crucial for investigative and safety purposes. Raman spectroelectrochemistry offers a quicker and more effective solution compared to the current detection methods, especially in field settings. Dr. Colby Ott's research in this area, using portable instrumentation, shows promise for clinical and forensic applications with potential commercial impact.

Your knowledge take-aways

Application Note: Enhancement of Raman intensity for the detection of fentanyl

On-demand Webinar: Spectroelectrochemistry: Drug Identification in Forensic Applications

Fast On-site Screening of Seized Drugs by Electrochemical and Spectroscopic Tools: Identification of Fentanyl and Novel Psychoactive Substances

Blog post: Raman spectroelectrochemistry from India to Spain: History and applications

Blog post: Spectroelectrochemistry: shedding light on the unknown

Blog post: Intuitive spectroelectrochemistry: How user-friendly cells make analysis even easier