Composition Analysis of ´´Legal Highs´´ by GC-EI-MS for Medico-Legal Purposes

Significance of the topic

The rapid emergence of synthetic and plant-derived designer drugs, often marketed as "legal highs," presents a significant challenge in forensic and clinical toxicology. Constant structural modification of psychoactive substances to evade legislation demands robust analytical approaches and comprehensive spectral libraries for accurate identification.

Objectives and overview

This study aimed to develop a reliable GC/EI-MS method for the identification of a broad range of designer drugs and to create a custom mass spectra library. The method was then applied to 943 "legal highs" samples (tablets, powders, herbal mixtures) obtained from inspections of smart shops in Poland.

Methodology and instrumention

Sample preparation

• Powders and tablets: 50 mg extracted with 2.5 mL methanol overnight
• Herbal mixtures: 100 mg extracted with 2 mL methanol overnight

GC/EI-MS analysis

• Instrument: Agilent 7890A GC coupled with 7000 MS
• Column: HP-5ms UI (30 m × 0.25 mm × 0.25 µm), helium carrier gas at 14.9 psi, splitless injection
• Temperature program: 60 °C (1 min), ramped at 4 °C/min to 325 °C (hold 12 min), total run time 19.63 min
• Ionization: Electron impact at 70 eV, full scan m/z 50–600
• Software: MassHunter Workstation and Library Editor for custom spectral library creation

Main results and discussion

A custom library of 53 reference spectra was built, covering 15 synthetic cannabinoids, 8 cathinones, 7 phenethylamines, 5 piperazines, 2 pyrrolidines and 16 unclassified designer compounds. Application to 943 samples revealed:

• Tablets and powders grouped into 64 product names; only half showed consistent active ingredients across batches
• Caffeine was the most frequent additive (202 occurrences), followed by cathinones butylone and MDPV, and the piperazine TFMPP
• Herbal mixtures formed 17 product groups; again consistency was just above 50%
• Most common synthetic cannabinoids in plant material were JWH-081, JWH-122 and RCS-4; no HU-210 or CP-series compounds detected
• Occasional unusual additives included lidocaine and MDPV in herbal mixtures

Benefits and practical applications

The developed GC/EI-MS method is open and extendable to newly emerging designer drugs. Creation of an in-house spectral library minimizes misidentification among structurally similar compounds. The methodology accelerates routine forensic screening and provides insight into market trends in psychoactive products.

Future trends and possibilities for use

Ongoing expansion of the spectral library to include novel analogs is essential. Integration with high-resolution MS and automated deconvolution tools will enhance detection capabilities. Real-time screening and cloud-based spectral databases could streamline forensic workflows and support rapid law enforcement responses.

Conclusion

The study successfully established a robust GC/EI-MS protocol and custom mass spectra library for comprehensive identification of designer drugs. Application to real samples from Polish smart shops demonstrated its utility in uncovering product inconsistencies and market dynamics, reinforcing its value in forensic and clinical toxicology.