Dataset Information

Application of 19F NMR Spectroscopy for Content Determination of Fluorinated Pharmaceuticals.

ABSTRACT: A simple, rapid, and selective quantitative nuclear magnetic resonance spectroscopic method was evaluated for the determination of the content of fluorinated pharmaceuticals. 19F NMR spectra were either obtained in dimethylsulfoxide-d6 or aqueous buffer, using trifluoroacetic acid as internal standard. Quantification of 13 fluorine-containing pharmaceuticals spanning various pharmacological classes was accomplished using the proposed method. The method was found to be fit for purpose (interday precision 1.2% relative standard deviation) and may thus be applied for routine analysis and quality control of fluorine-containing pharmaceuticals due to its simplicity, nondestructive sample measurement, reliability, and high specificity. Therefore, 19F NMR may serve as a suitable analytical tool for the identification and selective determination of fluorinated pharmaceuticals used as reference materials and bulk samples.

SUBMITTER: Okaru AO

PROVIDER: S-EPMC5664369 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Application of 19F NMR Spectroscopy for Content Determination of Fluorinated Pharmaceuticals.

Okaru Alex O AO Brunner Tobias S TS Ackermann Svenja M SM Kuballa Thomas T Walch Stephan G SG Kohl-Himmelseher Matthias M Lachenmeier Dirk W DW

Journal of analytical methods in chemistry 20171018

A simple, rapid, and selective quantitative nuclear magnetic resonance spectroscopic method was evaluated for the determination of the content of fluorinated pharmaceuticals. 19F NMR spectra were either obtained in dimethylsulfoxide-d6 or aqueous buffer, using trifluoroacetic acid as internal standard. Quantification of 13 fluorine-containing pharmaceuticals spanning various pharmacological classes was accomplished using the proposed method. The method was fou ...[more]

PMID: 29181224

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Project description:Nanometer-range distances are important for restraining the three-dimensional structure and oligomeric assembly of proteins and other biological molecules. Solid-state NMR determination of protein structures typically utilizes 13C-13C and 13C-15N distance restraints, which can only be measured up to ?7 Å because of the low gyromagnetic ratios of these nuclear spins. To extend the distance reach of NMR, one can harvest the power of 19F, whose large gyromagnetic ratio in principle allows distances up to 2 nm to be measured. However, 19F possesses large chemical shift anisotropies (CSAs) as well as large isotropic chemical shift dispersions, which pose challenges to dipolar coupling measurements. Here, we demonstrate 19F-19F distance measurements at high magnetic fields under fast magic-angle spinning (MAS) using radiofrequency-driven dipolar recoupling (RFDR). We show that 19F-19F cross-peaks for distances up to 1 nm can be readily observed in two-dimensional 19F-19F correlation spectra using less than 5 ms of RFDR mixing. This efficient 19F-19F dipolar recoupling is achieved using practically accessible MAS frequencies of 15-55 kHz, moderate 19F radio frequency field strengths, and no 1H decoupling. Experiments and simulations show that the fastest polarization transfer for aromatic fluorines with the highest distance accuracy is achieved using either fast MAS (e.g., 60 kHz) with large pulse duty cycles (>50%) or slow MAS with strong 19F pulses. Fast MAS considerably reduces relaxation losses during the RFDR ?-pulse train, making finite-pulse RFDR under fast-MAS the method of choice. Under intermediate MAS frequencies (25-40 kHz) and intermediate pulse duty cycles (15-30%), the 19F CSA tensor orientation has a quantifiable effect on the polarization transfer rate; thus, the RFDR buildup curves encode both distance and orientation information. At fast MAS, the impact of CSA orientation is minimized, allowing pure distance restraints to be extracted. We further investigate how relayed transfer and dipolar truncation in multifluorine environments affect polarization transfer. This fast-MAS 19F RFDR approach is complementary to 19F spin diffusion for distance measurements and will be the method of choice under high-field fast-MAS conditions that are increasingly important for protein structure determination by solid-state NMR.

Dataset Information

Application of 19F NMR Spectroscopy for Content Determination of Fluorinated Pharmaceuticals.

Publications

Application of <sup>19</sup>F NMR Spectroscopy for Content Determination of Fluorinated Pharmaceuticals.

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