# Discovery of Oxyacanthine Dihydrochloride Monohydrate Polymorphs from Obfuscated Samples by Microcrystal Electron Diffraction

## TL;DR

Scientists used a new technique to identify two crystal structures of a drug compound from mislabeled samples, showing the importance of this method in pharmaceutical quality control.

## Contribution

The study demonstrates the practical application of MicroED in identifying polymorphic structures from mislabeled pharmaceutical samples.

## Key findings

- Two polymorphic structures of oxyacanthine dihydrochloride monohydrate were identified using MicroED.
- One polymorph has a conformation between half-chair and half-boat, while the other adopts a distinct half-boat conformation.
- The latter polymorph is thermodynamically preferred based on structural and energy analysis.

## Abstract

It is estimated that more than 50% of marketed pharmaceuticals are derived from natural products. Structural characterization of natural products and their drug formulations is essential for the pharmaceutical industry. The use of microcrystal electron diffraction (MicroED) is reported to identify two polymorphic crystal structures of oxyacanthine dihydrochloride monohydrate from obfuscated samples that are mislabeled as “berbamine dihydrochloride”. The two polymorphs display primary conformational differences in one of the tetrahydroisoquinoline rings: one polymorph exhibits an intermediate conformation between half‐chair and half‐boat, while the other adopts a distinct half‐boat conformation. Analysis of their structures, energies, and crystal packing diagrams indicates a thermodynamic preference for a transformation into the latter. This study highlights the value of integrating MicroED into pharmaceutical pipelines as an efficient tool for structural analysis and quality control.

The practical application of microcrystal electron diffraction is demonstrated to identify two polymorphic crystal structures of oxyacanthine dihydrochloride monohydrate from obfuscated samples that had been mislabeled as "berbamine dihydrochloride". Analysis of their structures, energies, and crystal packing diagrams indicates a thermodynamic preference for a transformation into the latter form.© 2026 WILEY‐VCH GmbH