A new approach for accurate quantitative determination using fluorine nuclear magnetic resonance spectroscopy

Abstract

Abstract:A new approach for accurate quantitative determination by fluorine nuclear magnetic resonance ( 19 F NMR) spectroscopy is presented and discussed.19 F NMR spectroscopy has similar properties to 1 H NMR spectroscopy except for the wide chemical shift dispersion, which is the main difference between the two techniques. The off-resonance effect, which is caused by the chemical shift difference between the excitation pulse offset and the resonance signal position, is expected to be the most important parameter influencing the accuracy of the quantitative analysis by 19 F NMR spectroscopy. We propose a new method that reduces the influence of the off-resonance effect in 19 F NMR measurement. First, we discussed the areas of signals originating from different functional groups in a molecule. Then, we evaluated the areas of signals originating from two different reference materials (RMs). The accuracy of the ratios of two signal areas in the 19 F NMR spectrum of a molecule of Potassium perfluorooctanesulfonate was less than 1 %. We also evaluated the purity of flusulfamide and diflubenzuron as RMs, and found that the method could determine the purity to less than 1 % accuracy relative to the reference values.

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

“…Supplementary Figures S1–S13 show the 19 F NMR spectra of all investigated compounds (see Supplementary Material available online at https://doi.org/10.1155/2017/9206297). A potential shortcoming of 19 F NMR is that, due to the wide chemical shift dispersion, a single excitation pulse cannot produce a uniform excitation over the entire range of the chemical shift region of interest [28]. To overcome this problem usually two measurements have to be performed: one overview experiment over the whole range to identify the optimal sweep width and then a second experiment for quantification in this range.…”

“…The NMR probe was maintained at 300 K during the whole experiment. A delay time ( D 1) of 20 s was adopted to ensure full T 1 relaxation, and pulse angle of 90° was used to provide maximum signal-to-noise ratio (S/N) and minimize the influence of off-resonance effect on the accuracy of 19 F NMR measurement [28]. To maximize sensitivity, 512 scans were collected into 65536 data points over a spectral width of typically 95–125 ppm (for details see Tables 1 and 2).…”

Quantitative benchtop 19F NMR spectroscopy: a robust and economical tool for rapid reaction optimization

“…Large systematic errors are encountered on high-field instruments, since the signal intensity decreases dramatically with their distance from the center frequency (Fig. 2) 58,59 . Reduced excitation translates to a reduced integral for a reaction component.…”

Internal Standard Reference Data for 19F qNMR: 3,5-Bis(trifluoromethyl)Benzoic Acid [ISRD-09]

“…There are a number of literature reports on the use of specific compounds as 19 F qNMR internal standards. 25,[29][30][31] The focus of these papers are generally a specific application of 19 F qNMR rather the general application of an individual compound as a higher-order, SI-traceable primary measurement standard for qNMR. The second goal of this report is to establish the desirable properties for individual compounds to serve as versatile SI-traceable internal standards for purity assignment by 19 F qNMR.…”