Rapid Detection of the Low Dose API in Xanax Using Surface-Enhanced Raman Spectroscopy for Anti-Counterfeiting Purposes

Importance of the Topic

Counterfeit prescription drugs represent a growing public health and safety concern, with fake Xanax tablets frequently laced with dangerous substances such as fentanyl. Rapid, field-deployable screening methods are essential to distinguish genuine pharmaceuticals from harmful counterfeits before they reach consumers.

Objectives and Study Overview

This study aims to develop a surface-enhanced Raman spectroscopy (SERS) protocol for detecting trace levels (<0.20% w/w) of the active pharmaceutical ingredient (API) alprazolam in Xanax tablets using a handheld Raman spectrometer. The method also evaluates the ability to identify fentanyl substitutions in counterfeit samples.

Methodology and Used Instrumentation

Sample Preparation:

• Approximately 30 mg of a 0.25 mg alprazolam Xanax tablet dissolved in 0.5 mL acetone.
• Paper-based SERS substrate immersed in solution for ~30 s.
• Analysis at three different spots per substrate to account for heterogeneity.

Instrumentation:

• B & W Tek TacticID handheld Raman spectrometer with 785 nm laser excitation.
• TacPac adaptor and paper-based SERS substrates.

Data Acquisition:

• Automated integration times from 15 to 30 s per scan.
• Hit Quality Index (HQI) algorithm for spectral library matching.

Main Results and Discussion

Direct Raman measurements on the raw Xanax surface yielded only lactose peaks and failed to detect alprazolam. In contrast, SERS spectra of genuine Xanax exhibited characteristic alprazolam peaks at 688, 1000, 1132, 1160, 1312, 1380, 1484, 1568, and 1592 cm⁻¹. Excipients such as cellulose, lactose, starch, and magnesium stearate showed minimal SERS response due to low solubility. SERS spectra of fentanyl revealed a strong 1000 cm⁻¹ peak but lacked unique alprazolam markers, enabling spectral discrimination. HQI matching produced average scores of 91.0 for alprazolam and 82.3 for fentanyl, while excipients produced no match.

Benefits and Practical Applications of the Method

• High selectivity and sensitivity for trace API detection in complex formulations.
• Non-destructive, simple sample preparation suitable for field use.
• Rapid identification reduces risk to law enforcement and consumers.
• Onboard HQI algorithm enables real-time decision support.

Future Trends and Possibilities for Use

Advancements may include expanded spectral libraries, machine learning-based spectral deconvolution, integration with portable mass spectrometry, and application to a wider range of dosage forms and APIs. Miniaturization of SERS substrates and automated sample handling could further streamline field anti-counterfeiting workflows.

Conclusion

The developed SERS-based approach, implemented on a handheld Raman spectrometer, enables reliable detection of low-dose alprazolam and discrimination from harmful fentanyl in Xanax tablets. Its speed, portability, and selectivity make it a valuable tool for pharmaceutical quality control and law enforcement efforts against counterfeit drugs.

References

1. U.S. Food and Drug Administration. Counterfeit Medicine. http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/CounterfeitMedicine/
2. Addiction Resource. The Dangers of Fentanyl. https://addictionresource.com/drugs/the-dangers-of-fentanyl/
3. U.S. Drug Enforcement Administration. Counterfeit Prescription Pills. https://www.dea.gov/docs/Counterfeit%20Prescription%20Pills.pdf
4. Xanax Official Website. https://www.xanax.com/
5. National Institute on Drug Abuse. Fentanyl. https://www.drugabuse.gov/drugs-abuse/fentanyl