Comprehensive Analysis of Drug Residues from a Confiscated Pipe: GC-High Resolution Mass Spectrometry with Chemical Ionization to Facilitate Unknown Identification

Significance of the Topic

The rapid emergence of novel synthetic drugs poses a critical challenge for forensic laboratories and law enforcement. These substances often evade routine screening due to structural novelty and absence from standard mass spectral libraries. High-resolution mass spectrometry coupled with chemical ionization offers a powerful approach to detect and elucidate unknown compounds in complex matrices such as residues from drug paraphernalia.

Objectives and Study Overview

This study examined extractable residues from a confiscated pipe to:

1. Demonstrate the use of combined high-resolution electron impact (EI) and chemical ionization (CI) time-of-flight mass spectrometry for unknown identification.
2. Identify the two most abundant unknown analytes (“Unknown A” and “Unknown B”).
3. Characterize additional synthetic cannabinoids and true cannabis constituents present in the sample.

Methodology and Used Instrumentation

Sample Preparation:

• Approximately 93 mg of residue was scraped from the pipe interior.
• Residue was dissolved in a 2:1 methanol/dichloromethane mixture; 1 mL aliquots were transferred to autosampler vials.

Gas Chromatography – Mass Spectrometry Conditions:

• GC System: Agilent 7890 with Restek Rxi-5HT column (30 m × 0.25 mm ID, 0.10 µm df).
• Carrier Gas: Helium at 1.0 mL/min; injection 1 µL splitless at 280 °C.
• Oven Program: 60 °C (1 min), ramp 40 °C/min to 310 °C, hold 8 min.
• Transfer Line Temperature: 300 °C.

Mass Spectrometry:

• Instrument: LECO Pegasus® GC-HRT high-resolution time-of-flight MS.
• Ionization Modes: EI at 70 eV (source 250 °C), CI with methane (source 180 °C).
• Acquisition Rate: 10 spectra/s over m/z 50–550 at resolution R≈25 000.

Main Results and Discussion

Unknown A:

• EI spectrum showed a prominent ion at m/z 359.16861, but molecular ion confirmation required CI data.
• HR-CI produced a protonated ion at m/z 360.17632 and C₂H₅ adduct at m/z 388.20798, confirming nominal MW 359.
• Accurate mass formula assignments: EI ion C₂₄H₂₂FNO (Δ = 0.00062 Da, 1.72 ppm) and CI ion C₂₄H₂₃FNO (0.00050 Da, 1.38 ppm).
• Database search of C₂₄H₂₂FNO suggested AM-2201; confirmation was obtained by analysis of an authentic standard.

Unknown B:

• EI spectrum lacked a clear molecular ion, but HR-CI data revealed C₂₄H₂₁NO (m/z 339.16177, –1.45 ppm).
• Candidate structure was identified as JWH-022 by formula search and spectral features.

Additional Findings:

• Extracted ion chromatograms revealed Δ⁹-THC and synthetic cannabinoids JWH-018, JWH-122, and JWH-081 with mass accuracy values between –1.39 and –0.12 ppm.
• A variety of other licit and illicit compounds (sterols, indole derivatives, nitriles, phenols) were detected, highlighting sample complexity likely due to multiple uses or production impurities.

Practical Benefits and Applications

Combining high-resolution EI and soft CI enables reliable determination of molecular weights and elemental compositions for unknown psychoactive compounds. This workflow:

• Improves forensic screening for emerging drugs not present in commercial libraries.
• Facilitates structural elucidation without extensive sample derivatization.
• Supports rapid confirmation through comparison with reference standards.

Future Trends and Opportunities

Advancements likely to enhance this approach include:

• Expansion of high-resolution spectral libraries covering new psychoactive substances.
• Integration of automated data mining and mass defect filtering for non-targeted screening.
• Real-time ambient ionization techniques paired with high-resolution MS for on-site forensic analysis.
• Machine-learning algorithms for rapid structural prediction from accurate mass data.

Conclusion

The Pegasus GC-HRT instrument demonstrated robust performance for comprehensive forensic analysis of pipe residues. High-resolution EI and CI data enabled confident identification of AM-2201 and JWH-022 as major constituents, along with detection of multiple cannabinoids and other compounds. This methodology provides a reliable framework for addressing the dynamic challenge of novel synthetic drugs in forensic investigations.

References

1. Collins M. Some new psychoactive substances: precursor chemicals and synthesis-driven end-products. Drug Test. Anal. 2011;3:404–416.
2. Lindigkeit R, et al. Spice: A never ending story? Forensic Sci. Int. 2009;191:58–63.
3. Hudson S, Ramsey J. The emergence and analysis of synthetic cannabinoids. Drug Test. Anal. 2011;466–478.
4. Gragenauer M, et al. Analysis of synthetic cannabinoids using HRMS and mass defect filtering. Anal. Chem. 2012;84:5574–5581.
5. Musah RA, et al. Rapid identification of synthetic cannabinoids via DART-MS. Rapid Commun. Mass Spectrom. 2012;26:1109–1114.
6. Dresen S, et al. Monitoring of herbal mixtures potentially containing psychoactive compounds. J. Mass Spectrom. 2010;45:1186–1194.