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.

Determination of hydroxyl groups in biorefinery resources via quantitative 31P NMR spectroscopy

“…These active nuclei normally have much broader chemical shift ranges with less signal overlap and less interference from the homonuclear coupling. Most important, however, is the fact that the solvent normally has no effect on the NMR signal and thus solvent suppression is not necessary 74 . Phosphitylation followed by 31…”

Concepts and Core Principles of Fragment-Based Drug Design

“…The former method works similarly to the chemical shift perturbation NMR methods using 15 N or 13 C-labeled proteins described above and requires the introduction of a fluorinated label into the biomacromolecule, usually via non-natural amino acids [91]. Chemical shifts of 19 F are extremely sensitive to changes in the local environment induced by protein–ligand interactions or conformational changes of the protein [92]. Compared to 13 C labelling, 19 F offers a higher natural abundance and less signal overlap [93].…”

Insight and performance of LC‐DFT vs DFT in the NMR shielding and chemical shift calculations: Case of CHClCHCF3

“…This effect has been explained by the lack of relativistic effects in the NMR calculations, which is mainly the spin-orbit (SO) couplings. [4,12,14,15,21,32]…”

“…Nuclear magnetic resonance spectroscopy (NMR) has become a powerful tool for obtaining information concerning the structure and dynamics of molecules. [ 1–37 ] In the field of molecular modeling, the assessment of the NMR shielding was addressed by Ramsey in the early 1950s. [ 5,9 ] Thereafter, it has been modernized by Stevens et al in 1963.…”

“…[31,44] However, the nucleus 19 F offers the advantage of higher natural abundance than the isotope 13 C. It shows a large chemical shift range compared to 1 H, which helps avoid signal overlap. [12] Chapman and Bryce [14] have investigated the shielding tensors of 35 Cl, using the quantum chemical method B3LYP/aug-cc-pVDZ for Cl atom and cc-pVDZ for all other atoms in the amino acid hydrochloride structures. They found that this method agrees well with the experiment.…”