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[Research Achievement] Revolutionizing Nitrosamine Risk Mitigation: Direct Structure Determination with 3D ED / MicroED (Joint Research with Rigaku Corporation)

A new research paper authored by Keiyo Nakai, Kuniyoshi Miki, Natsuki Hashimoto, Mitsuhisa Yamano, et al., has been published in Org. Process Res. Dev. 2025 (ASAP).

 

掲載誌: 　　Org. Process Res. Dev. 2025 (ASAP)

タイトル: 　Structure Determination of Synthesized Nitrosamine
　　　　      Drug Substance-Related Impurities (NDSRIs) Using 3D ED/MicroED

URL: 　　    https://doi.org/10.1021/acs.oprd.5c00236

著者:        　 ¹Keiyo Nakai*, ¹Yuki Ejima, ²Takashi Kikuchi, ¹Kuniyoshi Miki,

                          ¹Natsuki Hashimoto,  ¹Mitsuhisa Yamano

所属:        　 ¹SPERA PHARMA, Inc.　²Rigaku Corporation　

 

Summary:

3D Electron Diffraction (3D ED) / MicroED is changing the game in nitrosamine risk mitigation.

Our latest study demonstrates how this cutting-edge technology enables rapid and precise structure determination of NDSRIs (Nitrosamine Drug Substance-Related Impurities).

n recent years, nitrosamine contamination risk has become a critical global issue for the pharmaceutical industry. When a potential risk is identified, rapid implementation of mitigation measures is required, with the core steps being reference standard synthesis and structural confirmation.
However, current practice often relies on indirect evidence from MS (mass spectrometry), ¹H-NMR(nuclear magnetic resonance), and ¹³C-NMR, leading to conclusions that are merely “likely correct.” In fact, even commercially available nitrosamines have been found to contain structural errors upon precise analysis.

By applying 3D ED / MicroED to the structural determination of various NDSRIs, we achieved the following groundbreaking results:

　　■ Analysis of microcrystalline nitrosamines without electron-beam damage

　　■ Exceptional utility in identifying rotational and positional isomers

 

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