Differentiating Structurally Similar Fentanyl Analogs by Comparing Density Functional Theory (DFT) Calculations and...

Area of Science:

• Forensic Chemistry
• Analytical Chemistry
• Spectroscopy

Background:

• Fentanyl and its analogs are primary drivers of overdose fatalities in the U.S.
• Identifying and distinguishing fentanyl analogs is crucial due to potency variations.
• Surface-enhanced Raman spectroscopy (SERS) offers a method for differentiating structurally similar compounds.

Purpose of the Study:

• To develop and validate methods for differentiating 4-fluoroisobutyryl fentanyl (4-FIBF), cyclopropyl fentanyl (CPrF), and related fentanyl analogs.
• To compare theoretical calculations with experimental spectroscopic data for analog identification.

Main Methods:

• Density functional theory (DFT) calculations were employed to assign spectral bands.
• Normal Raman and SERS techniques were used to acquire experimental spectra.
• Principal component analysis (PCA) and soft independent modeling of class analogy (SIMCA) were applied for data analysis.

Main Results:

• DFT calculations successfully assigned spectral bands for fentanyl analogs.
• Both theoretical and experimental methods allowed for visual differentiation of structurally similar analogs.
• SERS achieved limits of detection of 0.35 ng/mL for 4-FIBF and 4.4 ng/mL for CPrF.

Conclusions:

• Fentanyl analogs can be reliably differentiated using a combination of DFT calculations and SERS.
• The developed methods are suitable for field applications and smaller laboratories utilizing portable Raman spectrometers.
• This technique enhances the ability to detect and identify dangerous synthetic opioids in illicit drug samples.