Fluorine pharma: Quality control by NMR

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  • Published: Dec 1, 2017
  • Author: David Bradley
  • Channels: NMR Knowledge Base
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Routine fluorine

Routine analysis and quality control of fluorine-containing pharmaceuticals could now be possible with the application of the relatively simple and straightforward technique of fluorine-19 nuclear magnetic resonance (NMR) spectroscopy, according to researchers in Kenya and Germany.

Routine analysis and quality control of fluorine-containing pharmaceuticals could now be possible with the application of the relatively simple and straightforward technique of fluorine-19 nuclear magnetic resonance (NMR) spectroscopy, according to researchers in Kenya and Germany.

Alex Okaru of the University of Nairobi and Tobias Brunner, Svenja Ackermann, Thomas Kuballa, Stephan Walch, Matthias Kohl-Himmelseher, and Dirk Lachenmeier of Chemisches und Veterinäruntersuchungsamt (CVUA) Karlsruhe, explain how with the advent of a wide range of fluorinated pharmaceuticals there is now an urgent need for quality control and fraud and counterfeit product detection methods that can determine fluorine content quickly and at low cost. The team points out that NMR spectroscopy has continued to mature as an analytical technique and now in the form of fluorine-19 NMR offers sensitivity and unparalleled access to molecular information. It is rapid, high-throughput and non-destructive, unlike many other analytical techniques that might otherwise have been used in this context. Its use also precludes the need for a reference standard.

Obvious candidate

Many of the aforementioned advantages of NMR apply equally irrespective of the nucleus in question, whether hydrogen, carbon, or fluorine. However, fluorine offers several advantages over the less relatively abundant carbon-13 such as stronger signals and reduced signal overlap than is seen with proton NMR, the team explains. Moreover, given that there are some 200 medicines that now contain fluorine and one-third of the top-performing drugs on the market are fluorinated, fluorine-19 is an obvious candidate for their analysis in a range of contexts.

Specificity

Of course, chromatography, electrochemistry, electrophoresis, ultraviolet spectroscopy, and various other techniques have been used widely for analysis of such products. But, these come with extra costs and hindrances and the limitations that requisite reference materials bring with them. The team adds that the direct relationship between the NMR peak area and the number of fluorine nuclides might be readily exploited in a spectral analysis.

As proof of principle, the team has now used fluorine-19 NMR spectroscopy in dimethylsulfoxide-d6 or aqueous buffer, and with trifluoroacetic acid as an internal NMR standard to quantify 13 fluorine-containing pharmaceuticals. The compounds span a range pharmacological classes, among them fluprednidene, flucytosine, .flumazenil, and fluoxetine Their results show the technique to be "fit for purpose" with an interday precision of 1.2% relative standard deviation. Fluorine-19 NMR spectroscopy might thus "be applied for routine analysis and quality control of fluorine-containing pharmaceuticals due to its simplicity, nondestructive sample measurement, reliability, and high specificity."

Related Links

J Anal Methods Chem 2017, online: "Application of 19F NMR Spectroscopy for Content Determination of Fluorinated Pharmaceuticals"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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