Deadly Counterfeit Pills: Untargeted Analysis of Fentanyl-Laced Drugs

Significance of Topic

Counterfeit pills pose severe health risks due to unknown potent adulterants such as fentanyl derivatives that can cause fatal overdoses. Rapid and comprehensive identification of these compounds supports forensic investigations and public safety efforts.

Objectives and Study Overview

This study aimed to apply untargeted high performance time of flight mass spectrometry to characterize the chemical composition of fake pills. The focus was on detecting fentanyl its analogs and precursors in counterfeit oxycodone Benadryl and unknown tablets using advanced data processing.

Methodology and Used Instrumentation

• Sample Preparation
  • Pills were crushed and extracted with a mixture of chloroform methanol and isopropanol by sonication
  • Extracts were filtered and aliquots transferred to GC vials
• Instrumentation
  • Gas Chromatograph Agilent 7890 with L PAL3 Autosampler
  • Column Rxi 35 Sil MS 15 m x 0.25 mm x 0.25 µm
  • LECO Pegasus BT Time of Flight Mass Spectrometer
  • ChromaTOF software for untargeted data processing and library searches
• Analytical Parameters
  • Injection 1 µL split mode at 250 °C
  • Carrier gas helium constant flow at 1.4 mL per min
  • Temperature program from 110 to 300 °C at 40 °C per min
  • Electron ionization with mass range of 45 to 600 m/z and acquisition rate of 10 spectra per second

Main Results and Discussion

• Fake Benadryl tablets contained diphenhydramine fentanyl and the precursor despropionyl fentanyl with high spectral similarity and low mass errors
• Counterfeit oxycodone samples lacked oxycodone but contained acetaminophen caffeine metamizole fentanyl analogs and ANPP precursor compounds
• An unknown tablet was identified to contain multiple fentanyl analogs including p fluorofentanyl N propionyl norfentanyl and phenethyl 4 ANPP using mass error verification and library matching

Benefits and Practical Applications

This method offers rapid comprehensive profiling of counterfeit pills providing forensic laboratories with reliable evidence of lethal adulterants. The untargeted approach reveals unexpected compounds and supports law enforcement and public health interventions.

Future Trends and Potential Applications

• Integration of high resolution mass spectrometry with machine learning for automated identification of novel analogs
• Deployment of field portable instruments for on site drug screening
• Expansion of spectral libraries to cover emerging synthetic opioids and precursors

Conclusion

The combination of fast separation time of flight mass spectrometry and advanced software processing enables the untargeted detection of fentanyl and related compounds in counterfeit pills. This approach enhances analytical capabilities in forensic toxicology and contributes to the fight against illicit drug distribution.

Reference

1. Fentanyl DrugFacts National Institute on Drug Abuse June 2021
2. Recommended Methods for the Identification and Analysis of Fentanyl and its Analogs in Biological Specimens United Nations Office on Drugs and Crime 2017
3. Vandeputte MM Krotulski AJ Hulpia F Van Clengergh S Stove CP Phenethyl 4 ANPP A Marginally Active Byproduct Suggesting a Switch in Illicit Fentanyl Synthesis Routes Journal of Analytical Toxicology April 2021