动态核极化增强的NMR光谱学用于制药配方
Aaron J Rossini1, Cory M Widdifield, Alexandre Zagdoun
1Centre de RMN à Trés Hauts Champs, Institut de Sciences Analytiques, Université de Lyon (CNRS/ENS Lyon/UCB Lyon 1) , 69100 Villeurbanne, France.
Journal of the American Chemical Society
|January 14, 2014
概括
动态核极化 (DNP) 固态NMR使药物配方的详细表征成为可能. 这种技术可以快速识别无形活性药物成分 (API),并揭示API-辅助剂相互作用,而不会改变药物产品.
科学领域:
- 固态NMR光谱学 固态NMR光谱学
- 制药分析 制药分析
- 材料的表征材料的表征.
背景情况:
- 在原子水平上对制药配方进行表征对于质量控制至关重要.
- 传统的NMR方法可能需要样本修改或缺乏复杂配方的敏感性.
- 动态核极化 (DNP) 为固态NMR提供了增强的灵敏度.
研究的目的:
- 为了证明DNP增强的固态NMR对商业制药配方的特征的有用性.
- 分析药物产品中的原子层结构和相互作用.
- 为了确定活性药物成分 (API) 的物理形式和颗粒大小.
主要方法:
- 使用了DNP增强的9.4T固态NMR光谱.
- 在1,1,2,2-四乙烯中浸了多基极化剂的细磨片.
- 在105K获得一维和二维的13C和15N固态NMR光谱.
- 分析了DNP增强 (ε) 作为两极化时间的函数,以建模核旋转扩散.
主要成果:
- 在四种商业配方中为 cetirizine二化物实现了 40-90 的 DNP 增强 (ε).
- 成功地在片中确定了API的无形形式.
- 使用1H-15N相关性光谱观察到直接的API-povidone相互作用.
- 使用韦布尔分布建模确定了API域大小,粒子半径约为0.07μm.
结论:
- 用DNP增强的固态NMR是一种强大的,非破坏性的技术,用于药物配方的详细表征.
- 该方法允许快速获取高质量的光谱,并保留微观结构信息.
- 它提供了关于API物理形式,粒子大小和药物辅助剂相互作用的见解.
相关概念视频
¹³C NMR: Distortionless Enhancement by Polarization Transfer (DEPT)
1.3K
When proton-coupled carbon-13 spectra are simplified by a broadband proton decoupling technique, structural information about the coupled protons is lost. Distortionless enhancement by polarization transfer (DEPT) is a technique that provides information on the number of hydrogens attached to each carbon in a molecule. While the DEPT experiment utilizes complex pulse sequences, the pulse delay and flip angle are specifically manipulated. The resulting signals have different phases depending on...
1.3K
¹H NMR: Interpreting Distorted and Overlapping Signals
1.3K
Spin systems where the difference in chemical shifts of the coupled nuclei is greater than ten times J are called first-order spin systems. These nuclei are weakly coupled, and their chemical shifts and coupling constant can generally be estimated from the well-separated signals in the spectrum.
As Δν decreases and the signals move closer, the doublets appear increasingly distorted. The intensities of the inner lines increase at the cost of those of the outer lines as the signals are...
As Δν decreases and the signals move closer, the doublets appear increasingly distorted. The intensities of the inner lines increase at the cost of those of the outer lines as the signals are...
1.3K
Two-Dimensional (2D) NMR: Overview
1.6K
The 1D NMR spectrum of large and complex molecules like natural products has complicated splitting patterns and overlapping signals, which can be easily interpreted using 2-dimensional (2D) NMR. Unlike 1D NMR, 2D NMR has two frequency axes that provide the coupling information between the nucleus A and nucleus B in a molecule. The process from which 2D spectra are obtained has four steps.
The first step is the preparation period, during which nucleus A is excited with a radiofrequency pulse....
The first step is the preparation period, during which nucleus A is excited with a radiofrequency pulse....
1.6K
Other Nuclides: 31P, 19F, 15N NMR
888
Many organic, inorganic, and biological molecules contain spin-half nuclei such as nitrogen-15, fluorine-19, and phosphorus-31. As a result, NMR studies of these nuclei have found extensive applications in chemical and biological research.
While fluorine-19 and phosphorous-31 have high natural abundances (100%) and positive gyromagnetic ratios, nitrogen-15 has a low natural abundance and a negative gyromagnetic ratio. However, nitrogen-15 is still preferred over nitrogen-14 (which has a...
While fluorine-19 and phosphorous-31 have high natural abundances (100%) and positive gyromagnetic ratios, nitrogen-15 has a low natural abundance and a negative gyromagnetic ratio. However, nitrogen-15 is still preferred over nitrogen-14 (which has a...
888
Double Resonance Techniques: Overview
870
Double resonance techniques in Nuclear Magnetic Resonance (NMR) spectroscopy involve the simultaneous application of two different frequencies or radiofrequency pulses to manipulate and observe two distinct nuclear spins. One important application of double resonance is spin decoupling, which selectively suppresses coupling with one type of nucleus while observing the NMR signal from another nucleus, simplifying the spectrum and enhancing resolution.
Spin decoupling is usually achieved by...
Spin decoupling is usually achieved by...
870
Nuclear Overhauser Enhancement (NOE)
1.3K
Irradiation of a spin-active nucleus causes an increase or decrease in the signal intensity of neighboring nuclei that are not necessarily chemically bonded or involved in J-coupling. This phenomenon, called the nuclear Overhauser enhancement (NOE), results from through-space interactions between the nuclear spins. The NOE effect decreases with increasing internuclear distance and is generally not observed beyond 4 angstroms. In NOE, dipole-dipole interactions between neighboring spin-active...
1.3K


