Poster Presentation Crystal36-AXAA Conference 2026

Identification of Designer Drug Powders Using Microcrystal Electron Diffraction (MicroED) (143672)

Christopher Ross 1 , SHUTING LI 1 , Katherine Smith 1 , Malcolm McLeod 1 , Hongyi Xu 1
  1. Australian National University, Acton, ACT, Australia

Designer drugs are constantly evolving, with new compounds appearing faster than reference standards and detection methods can keep pace. This creates a real risk to users, who often have little information about what they are actually taking. CanTEST, a confidential drug checking and harm reduction service in Canberra, aims to close this gap by analysing samples submitted by members of the public. The service relies on fast first line techniques such as FTIR and UPLC, but these methods struggle with impure samples, mixtures of multiple components, and are unable to identify entirely novel compounds or resolve stereochemistry 1.

Three-dimensional electron diffraction (3D ED) 2, also known as MicroED 3, is an emerging crystallographic technique that enables structure determination from crystals too small for single-crystal X-ray diffraction and too complex for analysis by powder X-ray diffraction 4. Here, we present a MicroED workflow developed for the analysis of real drug samples submitted to CanTEST. Samples are prepared with minimal handling and analysed on a JEOL F200 transmission electron microscope equipped with a Dectris SINGLA detector under cryogenic conditions. Data is collected using CAMMatic 5 (modified version of Instamatic) 6, and processed using XDS 7 as well as Olex2 8, followed by dynamical refinement using PETS2 9 and Jana2020 10, which allows for absolute structure determination 11.

This workflow has been used to characterise a range of designer drugs directly from powder, including a novel ketamine analogue, a synthetic cannabinoid with full stereochemical assignment, and a designer benzodiazepine. We also explore the application of this workflow to multiphase samples, showing the potential for MicroED to identify multiple crystalline components within a single mixture.

This work represents one of the first applications of MicroED to forensic drug powder analysis, demonstrating novel compound identification, absolute structure determination, and multiphase discrimination directly from unpurified powders.

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