Breaking Down Fentanyl: New Technique Offers Promising Results in Differentiating Analogues

Scientists at Florida International University and the Escola Universitària Salesiana de Sarrià Passeig in Spain have found a novel approach to differentiate structurally similar fentanyl analogues using advanced spectroscopy techniques​ (1)​. The study, led by Sevde Dogruer Erkok of Florida International University, and her colleagues, compared Density Functional Theory (DFT) calculations with Surface-Enhanced Raman Spectroscopy (SERS) to yield unique spectroscopic fingerprints, offering a reliable and cost-effective method for forensic drug screening.

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Synthetic opioids, notably fentanyl and its analogues, are fueling a surge in overdose deaths across the United States. In 2022 alone, about 105,452 people died from drug overdoses, with synthetic opioids accounting for a staggering 75% of those deaths​ (1)​. Fentanyl is 50-100 times more potent than morphine, and some of its analogues, like carfentanil, can be even more dangerous, being up to 10,000 times more potent than morphine (1)​.

Given the high potency and risk associated with these compounds, detecting and differentiating fentanyl analogues has become critically important, especially in law enforcement and forensic analysis. However, many laboratories lack the equipment or expertise to accurately test for fentanyl analogues.

The study's authors explored the use of SERS as a technique to analyze fentanyl analogues. This approach uses Raman spectroscopy with colloidal metal nanoparticles, allowing for highly sensitive spectroscopic readings. The advantage of SERS lies in its capacity to detect trace amounts of illicit drugs and differentiate structurally similar fentanyl analogues by creating unique spectroscopic fingerprints​ (1). Handheld Raman instruments have been successful for investigators to identify the presence of fentanyl, but not to discriminate its analogues (2).

Read More: Handheld Raman to Fight Fentanyl—A Crucial New Use for an Established Tool

In their work, the team focused on five popular fentanyl analogues—carfentanil, furanyl fentanyl, acetyl fentanyl, 4-fluoroisobutyryl fentanyl (4-FIBF), and cyclopropyl fentanyl (CPrF). They found that SERS could effectively distinguish between these analogues, providing a quick and reliable method for identifying potentially dangerous mixtures of drugs. With portable Raman spectrometers becoming more prevalent, this method could be readily implemented in smaller laboratories and even in field applications, offering a powerful tool for drug enforcement and forensic analysis.

In addition to SERS, the study utilized Density Functional Theory (DFT) calculations to analyze the fentanyl analogues at a deeper level. By performing DFT calculations at the wB97XD/cc-pVTZ level, the team could assign spectral bands and determine characteristic peaks for each analogue​ (1). This theoretical approach provided a comprehensive understanding of the spectral variations among the different fentanyl analogues.

The results showed that even fentanyl analogues with similar structures could be differentiated, a crucial breakthrough for forensic analysis. The study also demonstrated that the limit of detection for 4-FIBF and CPrF was 0.35 ng/mL and 4.4 ng/mL, respectively, suggesting that this method is highly sensitive and can detect even trace amounts of these dangerous compounds​ (1).

The findings from this study have significant implications for law enforcement, forensic laboratories, and public health. With SERS and DFT offering new ways to differentiate fentanyl analogues, authorities can better combat the opioid crisis and reduce the risks associated with synthetic opioids. This innovative approach may pave the way for more effective drug screening and safer methods for analyzing potentially lethal compounds.

References

1. Dogruer, E. S.; Hernandez, E.; Cruz, J.; Mebel, A.M.; McCord, B. Differentiating Structurally Similar Fentanyl Analogs by Comparing Density Functional Theory (DFT) Calculations and Surface-Enhanced Raman Spectroscopy (SERS) Results. Appl. Spectrosc. 2024, 0 (0). doi:10.1177/00037028241246010
2. Lavery, P. Handheld Raman to Fight Fentanyl—A Crucial New Use for an Established Tool. https://www.spectroscopyonline.com/view/handheld-raman-fight-fentanyl-crucial-new-use-established-tool (accessed 2024-04-30).