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超清洁的纯转移NMR,具有最佳的抑制水分,用于分析水性制药样品
Guilherme Dal Poggetto1, Adam DiCaprio2, Mikhail Reibarkh1
1Merck & Co., Inc., 126 East Lincoln Avenue, 07065, Rahway, NJ, USA. guilherme.dal.poggetto@merck.com.
The Analyst
|March 22, 2024
概括
超清洁的纯转移NMR (SAPPHIRE) 与水抑制相结合,可提高水溶液中药物分析的光谱分辨率. 这种方法提高了小分子和的清晰度,有助于药物开发.
科学领域:
- 分析化学 分析化学
- 核磁共振 (NMR) 光谱学 核磁共振 (NMR) 光谱学
- 药品分析 药品分析
背景情况:
- 纯转移NMR实验通过将复杂的多重结构简化为单片来显著提高光谱分辨率.
- 在制药应用中常见的水性介质中分析样品时,抑制水的技术至关重要.
- 现有方法在混合溶剂中的各种药物化合物的最佳性能方面可能存在局限性.
研究的目的:
- 将超清洁的纯转移NMR (SAPPHIRE) 与先进的抑制水的方案相结合.
- 为了实现最佳的光谱分辨率和性能来分析小分子和宏环类药品.
- 为了验证该方法在水性和酸-水混合物中的有效性.
主要方法:
- 实施SAPPHIRE (同时获取纯转移和间接回声) 纯转移NMR技术.
- 整合了两个不同的内部编码的抑制水的方案.
- 适用于分析相关溶剂系统中的小分子和宏环制药标准.
主要成果:
- 在光谱分辨率的显著提升通过多重的崩成单片.
- 在纯水和乙-水混合物中实现了药物化合物的最佳性能.
- 验证了复杂样品的SAPHIRE和水抑制方法的有效性.
结论:
- SAPPHIRE纯转移NMR和内部水抑制的组合为制药分析提供了一个强大的工具.
- 这种方法为水性环境中的小分子和宏环提供了卓越的光谱清晰度.
- 该技术非常适合用于药物化合物的质量控制和表征.
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In an NMR sample, precise measurement of the absolute absorption frequencies of nuclei is difficult. A standard internal reference compound is added, and the frequency difference between the reference signal and sample signals is measured.
The internal reference compound generally used in NMR spectroscopy is tetramethylsilane (TMS). TMS is preferred because it is chemically inert, soluble in NMR solvents, and easily removable. Also, the highly shielded methyl protons in TMS yield an intense...
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The position of the absorption signal of a sample is reported relative to the position of the signal of tetramethylsilane (TMS), which is added as an internal reference while recording spectra. The difference between the absorption frequencies of the sample and TMS (in Hz) is divided by the spectrometer operating frequency (in MHz) to obtain a dimensionless quantity called the chemical shift. It is reported on the δ (delta) scale and expressed in parts per million.
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