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Peer-reviewedCC BY-NC-ND 4.0ACS Omega

Two-Step Crystallization Process Strategy for Cannabidiol Isolation at Higher Yields

  • William P. Chappell1
  • Botao Liu1
  • Mizuki Moriyama2
  • Yusuke Sato2
  • Brian O. Patrick1
  • Zijian Zhang3
  • Markus Roggen4
4 affiliations
  1. 1The University of British Columbia , , 2036 Main Mall , , ,
  2. 2Shionogi Pharma , Amagasaki Site 1-3, Kuise Terajima 2-chome , , ,
  3. 3Japan Tobacco Inc. , Kamiyacho Trust Tower, 1-1 Toranomon 4-chome , Minato-ku, ,
  4. 46221 University Boulevard , , , ,
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Abstract

We describe a Two-step DMA-MediAted Crystallization method (2DMAC-method) for the first time. This two-step strategy for the purification of cannabidiol (CBD) utilizes N,N-dimethylacetamide (DMA) to form an isolable CBD·2DMA solid solvate, which precipitates from cooled heptane. The 2DMAC-method is selective for CBD, as the solvate is free of tetrahydrocannabinol (THC). DMA can subsequently be removed via aqueous washing, and the free CBD is crystallized from heptane. Overall, the 2DMAC-method delivers higher recovery and tighter impurity control compared to a standard industry method. Across three samples, final CBD recoveries averaged 61% with the 2DMAC-method, versus 48% for a standard heptane crystallization. All CBD isolates obtained via the solvate reached ≥97.5% CBD, with nondetectable THC by HPLC, LC-MS, and NMR, in line with common method purities. Additionally, the 2DMAC-method was more effective in removing cannabidivarin (CBDV) and the toxic, oxidative impurity HU-331 (CBD hydroxyquinone).

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Cite

BibTeXRIS
BibTeX
@article{chappell2026twostep,
  title = {{Two-Step Crystallization Process Strategy for Cannabidiol Isolation at Higher Yields}},
  author = {William P. Chappell and Botao Liu and Mizuki Moriyama and Yusuke Sato and Brian O. Patrick and Zijian Zhang and Markus Roggen},
  journal = {ACS Omega},
  year = {2026},
  month = oct,
  doi = {10.1021/acsomega.6c08005},
  url = {https://pubs.acs.org/acsodf/article/doi/10.1021/acsomega.6c08005/5460972/Two-Step-Crystallization-Process-Strategy-for},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Two-Step Crystallization Process Strategy for Cannabidiol Isolation at Higher Yields
AU  - William P. Chappell
AU  - Botao Liu
AU  - Mizuki Moriyama
AU  - Yusuke Sato
AU  - Brian O. Patrick
AU  - Zijian Zhang
AU  - Markus Roggen
PY  - 2026
DA  - 2026/10/29
JO  - ACS Omega
DO  - 10.1021/acsomega.6c08005
UR  - https://pubs.acs.org/acsodf/article/doi/10.1021/acsomega.6c08005/5460972/Two-Step-Crystallization-Process-Strategy-for
AB  - We describe a Two-step DMA-MediAted Crystallization method (2DMAC-method) for the first time. This two-step strategy for the purification of cannabidiol (CBD) utilizes N,N-dimethylacetamide (DMA) to form an isolable CBD·2DMA solid solvate, which precipitates from cooled heptane. The 2DMAC-method is selective for CBD, as the solvate is free of tetrahydrocannabinol (THC). DMA can subsequently be removed via aqueous washing, and the free CBD is crystallized from heptane. Overall, the 2DMAC-method delivers higher recovery and tighter impurity control compared to a standard industry method. Across three samples, final CBD recoveries averaged 61% with the 2DMAC-method, versus 48% for a standard heptane crystallization. All CBD isolates obtained via the solvate reached ≥97.5% CBD, with nondetectable THC by HPLC, LC-MS, and NMR, in line with common method purities. Additionally, the 2DMAC-method was more effective in removing cannabidivarin (CBDV) and the toxic, oxidative impurity HU-331 (CBD hydroxyquinone).
SN  - 2470-1343
ER  -