Probing Mefloquine-Resin Complexes by C-13 Solid State NMR

Mefloquine chlorhydrate is a medicine prescribed for the full course of malaria treatment. When taking for children, usually vomiting occurs and new doses of medication frequently need to be taken. During the course of our research a new pediatric dispersible mefloquine formulations have been developed, using mefloquine and ion exchange resins. In this communication samples of mefloquine chlorhydrate, polacrilin potassium resin and mefloquine-resin formulations were evaluated in order to probe the presence of complex type structures by C-13 CPMAS NMR. Spectra were acquired on a Bruker WB Avance III400 spectrometer (9.4T), operating at Larmor frequency of 100.4 MHz. Acquisition conditions: pulse sequence – cross polarization magic angle spinning; spinning rate - between 8 to 10kHz; recycle time - between 3 to 60s; contact time for cross-polarization - between 0.1 to 20ms. Glycine was used as reference (C=O 176.03 ppm). An optimized mefloquine chlorhydrate spectrum could be obtained at recycle time of 20s, spinning rate of 9.8 Hz and contact time of 10 ms. All the carbon signals could be clearly assigned, including those linked to fluorine, in the region between 115 and 125 ppm. Prado et al. (2020) published a mefloquine hydrochloride spectrum with a contact time of 1.5 ms, but they did not visualize the signals of the CF3 carbons. Guo et al. (2021) published data for C-13 CPMAS NMR spectra of mefloquine, at a rotation speed of 20 kHz and contact times between 0.5 and 1.4 ms, that was comparable to our optimized spectrum. Comparison of the T1rhoH values for the carbons of mefloquine and polacrilin and mefloquine-resin allows us to confirm the absence of physical mixture and the presence of the complex in a formulated sample of mefloquine-resin.

Guo, C. et al. Anal.Chem. 93 (2021) 8210-18.
Prado, V.M. et al. Green Chemistry 22 (2020) 54-61.