The Role of SERS in detecting Nitazene

The opioid crisis has entered a dangerous new phase. While fentanyl continues to dominate headlines, an even more potent class of synthetic opioids has emerged from the shadows, nitazenes. These 2-benzylbenzimidazole compounds, originally synthesized in the 1950s but abandoned due to extreme toxicity, have resurfaced on illicit drug markets with devastating consequences.^[1] Traditional laboratory analysis methods, though highly accurate, require hours of processing time and are too slow for the rapid decision-making needed by first responders, law enforcement, and harm reduction workers facing contaminated street drugs. The solution lies in an innovative optical technology, Surface-Enhanced Raman Spectroscopy (SERS).

Why detection of Nitazene matters more than ever

Nitazenes represent one of the most concerning developments in the synthetic drug landscape. Research has shown that certain nitazene analogs, such as etonitazene, demonstrate opioid receptor potency 50 times greater than fentanyl.^[2] Fatal overdoses have been documented with blood concentrations in the low-to-sub nanogram per milliliter range levels, which are so minute they challenge conventional detection methods.^[3]

Since isotonitazene first appeared on recreational drug markets in 2019, the Centers for Disease Control and Prevention reported that nitazenes were implicated in approximately 5% of all drug overdose deaths in the United States by 2021, with prevalence continuing to increase.^[4] European monitoring systems have identified 22 distinct nitazene analogs across member states, with these compounds frequently appearing in counterfeit pharmaceutical tablets, powder heroin, and drug mixtures often without the user’s knowledge.

The Detection Challenge

The extreme potency of nitazenes creates unique analytical challenges. Effective doses measured in micrograms necessitate detection methods capable of identifying concentrations at the nanogram per milliliter level. Traditional analytical approaches like gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), while providing excellent specificity, require extensive sample preparation, specialized laboratory infrastructure, and analysis times measured in hours, which is entirely impractical for front-line screening scenarios where immediate decisions can mean the difference between life and death.^[5]

Detecting Emerging Drugs with SERS

Surface-Enhanced Raman Spectroscopy leverages the plasmonic properties of metallic nanostructures to amplify molecular signals by factors ranging from 10¹⁰ to 10¹¹.^[6] This extraordinary sensitivity enables detection of synthetic opioids at toxicologically relevant concentrations, the nanogram per milliliter levels where nitazenes exert their deadly effects. Unlike immunoassays that require specific antibodies for each target compound, SERS provides universal molecular fingerprint detection capable of identifying novel analogs as they emerge.

From Lab to Field the Real-World Application in Street Drug Testing

Recent breakthrough research has demonstrated SERS capability for rapid nitazene detection in real-world scenarios.^[7] Hhandheld SERS spectrometers were successfully deployed to screen suspect counterfeit tablets seized at international mail facilities, identifying three nitazene analogs—N-pyrrolidino etonitazene, isotonitazene, and etodesnitazene within 1-5 minutes per sample. This represents a dramatic improvement over traditional laboratory methods requiring hours of analysis.

The operational workflow is elegantly simple: dissolve the suspicious tablet in water or alcohol, apply a small sample to the Nikalyte SERS substrate, measure immediately without drying, and obtain results in real-time. This speed proves invaluable for:

• Border Control & Mail Screening: Rapid triage of suspect packages enables efficient resource allocation and immediate interdiction of dangerous substances
• Crime Scene Investigation: On-site presumptive identification guides investigative priorities and officer safety protocols
• Harm Reduction Services: Drug checking programs at festivals, safe consumption sites, and community organizations empower users with critical substance composition information
• Emergency Response: First responders can quickly assess scene hazards and make informed treatment decisions

Proven Performance on Related Compounds

While nitazene-specific SERS research is still emerging given the compounds recent appearance, extensive validation with structurally similar fentanyl analogs provides strong evidence for nitazene detection capability. Electrochemical-SERS approaches have achieved detection limits of 10-100 ng/mL for fentanyl compounds while successfully distinguishing six different fentanyl analogs and identifying fentanyl at concentrations as low as 1% in complex drug mixtures.^[8] Portable SERS systems combined with machine learning algorithms have demonstrated fentanyl quantification in heroin with over 93% prediction accuracy.^[9]

The technique’s versatility extends across the entire spectrum of novel psychoactive substances. Research has documented successful SERS detection of synthetic cannabinoids, synthetic cathinones, phenethylamines, and designer benzodiazepines demonstrating the universal applicability of surface enhanced Raman to the evolving synthetic drug landscape.^[10]

Biological Matrix Compatibility

Beyond powder and tablet analysis, SERS shows promise for biological specimen testing. Flow-separation strips have successfully detected codeine and fentanyl in blood plasma and whole blood within 5 minutes at concentrations relevant to overdose presentations.^[11] While nitazene concentrations in fatal cases (low-to-sub ng/mL range) approach current SERS detection limits, ongoing substrate optimization and signal enhancement strategies continue to push sensitivity boundaries.

Why Choose Nikalyte SERS for Nitazene and Synthetic Drug Detection?

Nikalyte’s vacuum-based fabrication eliminates the contamination inherent to wet chemical synthesis. Chemically produced nanoparticles retain residual citrate, polyvinylpyrrolidone (PVP), and other capping agents that occupy surface sites and introduce interfering spectral features. Nikalyte’s ligand-free nanoparticles provide clean surfaces maximizing analyte interaction and signal quality.^[12]

Superior Performance Metrics

• Sensitivity: Parts-per-billion detection capability for forensically relevant analytes
• Enhancement: Up to 1,000-fold signal amplification compared to conventional Raman spectroscopy
• Specificity: High signal-to-noise ratios enabling accurate identification of structurally similar molecules
• Speed: Immediate measurement without drying requirements—critical for time-sensitive applications
• Reproducibility: Uniform vacuum deposition produces consistent batch-to-batch performance

Ultra-Pure Vacuum-Deposited SERS Substrates

Nikalyte SERS substrates have been deployed globally across healthcare, pharmaceuticals, narcotics detection, forensics, environmental monitoring, and food safety applications. ^[12] Field users including border control agencies, police forces, and emergency first responders trust Nikalyte SERS substrates for reliable performance in demanding operational environments where laboratory access is unavailable and rapid decisions are critical.

Nikalyte SERS substrates are compatible with both portable handheld Raman spectrometers for field deployment and research-grade systems for laboratory validation. The paper-based format requires no special handling, storage, or disposal procedures enabling rapid adoption without extensive user training or infrastructure investment. ^[12]

Conclusion:

The synthetic drug crisis evolves continuously as clandestine chemists modify molecular structures to circumvent legal controls. Traditional analytical workflows, designed for known compounds, struggle to keep pace with this innovation cycle. Nitazenes exemplify the challenge: ultra-potent compounds appearing with minimal warning, requiring immediate detection capability to prevent overdose deaths and guide public health responses.

Nikalyte SERS technology offers a powerful solution uniquely suited to this dynamic threat landscape. The combination of molecular fingerprint specificity, extraordinary sensitivity, rapid analysis speed, and field portability addresses critical gaps in current detection capabilities. As nitazenes and other novel synthetic drugs continue emerging, the analytical community needs tools that are simultaneously sophisticated enough to provide definitive identification and practical enough for widespread deployment. Nikalyte SERS substrates meet both requirements.

From international mail facilities screening packages to harm reduction workers testing street drugs to forensic laboratories confirming case evidence, Nikalyte SERS substrates are on the front lines of the fight against synthetic opioids. As research continues expanding SERS applications and improving detection limits, this transformative technology will play an increasingly vital role in protecting communities from the devastating consequences of ultra-potent synthetic drugs like nitazenes.

Contact us to learn how Nikalyte SERS can help detect nitazenes and other synthetic drugs. Our experts can tailor fast, reliable screening solutions to your specific needs.

 References

1. Vandeputte, M. M., Van Uytfanghe, K., Layle, N. K., St. Germaine, D. M., Iula, D. M., & Stove, C. P. (2021). Synthesis, chemical characterization, and μ-opioid receptor activity assessment of the emerging group of “nitazene” 2-benzylbenzimidazole synthetic opioids. ACS Chemical Neuroscience, 12(7), 1241-1251. https://doi.org/10.1021/acschemneuro.1c00064
2. Glatfelter, G. C., Vandeputte, M. M., Chen, L., Walther, D., Tsai, M. M., Shi, L., Stove, C. P., & Baumann, M. H. (2023). Alkoxy chain length governs the potency of 2-benzylbenzimidazole ‘nitazene’ opioids associated with human overdose. Psychopharmacology, 240(12), 2573-2584. https://doi.org/10.1007/s00213-023-06451-2
3. De Vrieze, L. M., Walton, S. E., Pottie, E., Papsun, D., Logan, B. K., Krotulski, A. J., Stove, C. P., & Vandeputte, M. M. (2024). In vitro structure-activity relationships and forensic case series of emerging 2-benzylbenzimidazole ‘nitazene’ opioids. Archives of Toxicology, 98(9), 2999-3018. https://doi.org/10.1007/s00204-024-03774-7
4. Centers for Disease Control and Prevention. (2022). Notes from the field: Nitazene-related deaths—Tennessee, January 2019–December 2021. Morbidity and Mortality Weekly Report, 71(37), 1172-1173. https://doi.org/10.15585/mmwr.mm7137a5
5. Walton, S. E., Krotulski, A. J., & Logan, B. K. (2022). A forward-thinking approach to addressing the new synthetic opioid 2-benzylbenzimidazole nitazene analogs by liquid chromatography-tandem quadrupole mass spectrometry (LC-QQQ-MS). Journal of Analytical Toxicology, 46(3), 221-231. https://doi.org/10.1093/jat/bkab117
6. Pilot, R., Signorini, R., Durante, C., Orian, L., Bhamidipati, M., & Fabris, L. (2019). A review on surface-enhanced Raman scattering. Biosensors, 9(2), 57. https://doi.org/10.3390/bios9020057
7. Kimani, M. M., Lanzarotta, A. C., & Batson, J. S. (2023). Rapid screening of 2-benzylbenzimidazole nitazene analogs in suspect counterfeit tablets using Raman, SERS, DART-TD-MS, and FT-IR. Drug Testing and Analysis, 15(4), 439-453. https://doi.org/10.1002/dta.3440
8. Ott, C. E., Gupta, R., Daniels, J., Markham, J., Poe, B., Uddin, M. N., & Arroyo, L. E. (2022). 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, 2, 834820. https://doi.org/10.3389/frans.2022.834820
9. Zhu, Y., Song, H., Liu, R., Mu, Y., Gedda, M., Alodhay, A. N., Ying, L., & Gan, Q. (2025). On-site quantitative detection of fentanyl in heroin by machine learning-enabled SERS on super absorbing metasurfaces. npj Nanophotonics, 2(7).https://doi.org/10.1038/s44310-025-00055-8
10. Muhamadali, H., Watt, A., Xu, Y., Chisanga, M., Subaihi, A., Jones, C., Ellis, D. I., Sutcliffe, O. B., & Goodacre, R. (2019). Rapid detection and quantification of novel psychoactive substances (NPS) using Raman spectroscopy and surface-enhanced Raman scattering. Frontiers in Chemistry, 7, 412. https://doi.org/10.3389/fchem.2019.00412
11. Shende, C., Brouillette, C., & Farquharson, S. (2019). Detection of codeine and fentanyl in saliva, blood plasma and whole blood in 5-minutes using a SERS flow-separation strip. Analyst, 144(18), 5449-5454. https://doi.org/10.1039/C9AN01087D
12. Nikalyte Ltd. (n.d.). Surface enhanced Raman spectroscopy (SERS) substrates [Web page]. https://www.nikalyte.com/sers-substrates-new/