Fluorine NMR: Enhancing your NMR toolbox with this ideal NMR handle

Fluorine-19 is one of the most popular nuclides in NMR, along with ¹H, ¹³C and ³¹P. It has a relatively large chemical shift window (-300 to 400 ppm), which minimizes signal overlap even at low fields, is 100% naturally abundant, and its sensitivity is nearly as high as proton.¹ This makes fluorine an excellent nucleus for analyzing molecules or monitoring reaction progress. Fluorine also plays an important part in pharmaceuticals, as companies in this industry add fluorine to their drugs to enhance lipophilicity, thereby enhancing membrane permeation. Due to its unique chemical shift range, fluorine is sometimes also used as a marker to follow metabolic pathways when proton NMR spectra are too complex, even at higher fields.² It’s estimated that about 25% of drugs on the market contain at least one fluorine atom.

Fluorine-19 is also an attractive nuclide to conduct quantitative NMR (qNMR) experiments due to its high sensitivity.³ In the pharmaceutical industry, qNMR can be utilized to accurately determine the purity of drug compounds and to monitor their stability. Fluoxetine hydrochloride is a fluorinated compound used predominantly in the treatment of depression.⁴ The purity of the compound can be easily determined when an internal calibrant and the proper acquisition parameters are used.⁵ Figure 1 displays the ¹⁹F NMR spectrum of fluoxetine hydrochloride using 2-chloro-4-fluorotoluene as the internal calibrant.

Figure 1. ¹⁹F (96 MHz) NMR of analyte (fluoxetine hydrochloride) and internal calibrant (2-chloro-4-fluorotoluene) in CD₃OD.

To determine the purity of the drug, the signals of the calibrant and analyte were integrated, and the purity of the analyte was determined as 99.1 % (Table 1) using the following equation:

Overall, the addition of the fluorine channel to the Nanalysis 60 MHz, and now the Nanalysis 100 MHz instrument takes advantage of fluorine’s unique properties and the instrument’s magnetic strength to add another analytical dimension to your analysis.

If you have any questions about the incorporation of benchtop NMR into your workflow, please don’t hesitate to contact us!