<sup>19</sup>F-{<sup>1</sup>H} NMR spectroscopy in weakly orienting solvents for the enantiomeric resolution of fluorinated chiral drugs: The case of fluoxetine

Vincent Chiapolino; François-Marie Moussallieh; Philippe Lesot; Boris Gouilleux

doi:10.1016/j.jpha.2025.101469

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Vincent Chiapolino, François-Marie Moussallieh, Philippe Lesot, Boris Gouilleux. 19F-{1H} NMR spectroscopy in weakly orienting solvents for the enantiomeric resolution of fluorinated chiral drugs: The case of fluoxetine[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101469

Citation:

Vincent Chiapolino, François-Marie Moussallieh, Philippe Lesot, Boris Gouilleux. ¹⁹F-{¹H} NMR spectroscopy in weakly orienting solvents for the enantiomeric resolution of fluorinated chiral drugs: The case of fluoxetine[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101469

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¹⁹F-{¹H} NMR spectroscopy in weakly orienting solvents for the enantiomeric resolution of fluorinated chiral drugs: The case of fluoxetine

doi: 10.1016/j.jpha.2025.101469

a. University of Paris-Saclay, Institute of Molecular Chemistry and Materials of Orsay (ICMMO), Orsay, 91400, France;
b. National Center for Scientific Research (CNRS), Paris, 75016, France

Funds:

The authors thank the French National Research Agency (ANR) for its financial support (Grant No.: ANR-23-CE29-0005-01) in the developments of this research. The authors also thank the National Center for Scientific Research (CNRS), France and the University of Paris-Saclay, France for their recurrent funding. They would also like to thank the Institute of Molecular Chemistry and Materials of Orsay (ICMMO), France and the University of Paris-Saclay (Mutualized regional equipment (ERM) funding) for their financial participation to the BBFO 5-mm NMR probe as part of the renewal of the technical and scientific platform. Finally, the authors acknowledge Louise Meraud who participated to this work as a Master student.

Received Date: Mar. 15, 2025
Accepted Date: Oct. 09, 2025
Rev Recd Date: Oct. 03, 2025
Available Online: Oct. 13, 2025

Abstract

Abstract

A rapid and simple method combining ¹⁹F-{¹H} nuclear magnetic resonance (NMR) and weakly orienting chiral solvents is proposed for the spectral discrimination and accurate quantitation of fluoxetine enantiomers. Fluoxetine (FLX) is a well-known bioactive chiral drug in pharmacology with well-established anti-depressant properties (Prozac or Sarafem) and currently used as a racemate. Since 1991, it has been established that the (S)-form of FLX shows different pharmacokinetic and pharmacodynamic profiles in comparison to the (R)-form, hence the development of novel enantioresolved NMR methods for analyzing FLX is of interest. The reported approach, relying on a commercial polymer: poly-γ-benzyl-L-glutamate (PBLG) as chiral selector, addresses the enantiomeric analysis of FLX hydrochloride solutions with a high level of accuracy in a short time. The influence of experimental parameters, such as solute concentration and temperature on the enantiomeric resolution is investigated and discussed in depth. In particular, the uniformity and stability of PBLG-based lyotropic liquid crystals (LLCs) in presence of a hydrochloride analyte is assessed for the first time by ¹⁹F NMR imaging. All the outcomes obtained highlight the analytical potential of this NMR approach for the enantiomeric analysis of fluorinated chiral drugs while the spectral data recorded at various conditions in temperature and mesophase composition provide new valuable insights toward a better understanding of chiral recognition processes in polypeptide orienting media.
- Fluorinated chiral drugs,
- Fluoxetine,
- ¹⁹F NMR,
- PBLG-based LLC,
- Enantiomeric analysis,
- Active pharmaceutical ingredient

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References(51)

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