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新的 400MHz HTS 动力驱动磁体 NMR 技术在典型药物 API,盐酸西那卡塞上的性能。

Performance of new 400-MHz HTS power-driven magnet NMR technology on typical pharmaceutical API, cinacalcet HCl.

机构信息

Department of Attribute Sciences, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320-1799, USA.

Bruker BioSpin, 15 Fortune Drive, Billerica, MA, 01821, USA.

出版信息

Magn Reson Chem. 2018 Sep;56(9):817-825. doi: 10.1002/mrc.4740. Epub 2018 May 9.

Abstract

After years towards higher field strength magnets, nuclear magnetic resonance (NMR) technology in commercial instruments in the past decade has expanded at low and high magnetic fields to take advantage of new opportunities. At lower field strengths, permanent magnets are well established, whereas for midrange and high field, developments utilize superconducting magnets cooled with cryogenic liquids. Recently, the desire to locate NMR spectrometers in nontypical NMR laboratories has created interest in the development of cryogen-free magnets. These magnets require no cryogenic maintenance, eliminating routine filling and large cryogen dewars in the facility. Risks of spontaneous quenches and safety concerns when working with cryogenic liquids are eliminated. The highest field commercially available cryogen-free NMR magnet previously reported was at 4.7 T in 2013. Here we tested a prototype cryogen-free 9.4-T power-driven high-temperature-superconducting (HTS) magnet mated to commercial NMR spectrometer electronics. We chose cinacalcet HCl, a typical active pharmaceutical ingredient, to evaluate its performance towards structure elucidation. Satisfactory standard 1D and 2D homonuclear and heteronuclear NMR results were obtained and compared with those from a standard 9.4-T cryogenically cooled superconducting NMR instrument. The results were similar between both systems with minor differences. Further comparison with different shims and probes in the HTS magnet system confirmed that the magnet homogeneity profile could be matched with commercially available NMR equipment for optimal results. We conclude that HTS magnet technology works well providing results comparable with those of standard instruments, leading us to investigate additional applications for this magnet technology outside a traditional NMR facility.

摘要

经过多年向更高场强磁体的发展,过去十年中商业仪器中的核磁共振(NMR)技术已在低场和高场扩展,以利用新的机会。在较低场强下,永磁体已得到很好的应用,而对于中程和高场,则利用低温液体冷却的超导磁体进行开发。最近,由于希望将 NMR 光谱仪定位在非典型 NMR 实验室中,因此人们对开发无液氦磁体产生了兴趣。这些磁体不需要低温维护,从而消除了设施中常规的填充和大型低温杜瓦瓶。消除了与低温液体一起工作时的自发淬火风险和安全问题。以前报道的商业上可用的无液氦 NMR 磁体的最高场强为 2013 年的 4.7T。在这里,我们测试了一个原型无液氦 9.4-T 功率驱动高温超导(HTS)磁体,该磁体与商业 NMR 光谱仪电子设备相匹配。我们选择了盐酸西那卡塞,一种典型的活性药物成分,用于评估其在结构阐明方面的性能。获得了令人满意的标准 1D 和 2D 同核和异核 NMR 结果,并与来自标准 9.4-T 液氦冷却超导 NMR 仪器的结果进行了比较。两个系统之间的结果相似,只有微小差异。在 HTS 磁体系统中进一步与不同的匀场片和探头进行比较,证实了磁体的均匀性可以与商业 NMR 设备相匹配,以获得最佳结果。我们得出结论,HTS 磁体技术运行良好,提供的结果可与标准仪器相媲美,这促使我们研究这种磁体技术在传统 NMR 设施之外的其他应用。

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