Absolute purity determination of an organic fluorine pharmaceutical voriconazole via quantitative 19F NMR and method validation
Year: 2024
Type: article
Abstract: The 19 F NMR spectrum has a smaller number of signals than 1 H NMR, therefore, quantitative 19 F NMR ( 19 F-qNMR) can replace quantitative 1 H NMR ( 1 H-qNMR) for the absolute quantitation of organic fluorine-bearing compounds. In this study, we determined the purity of voriconazole (VCZ), an organic fluorine pharmaceutical, using 19 F-qNMR, validated the results in multiple laboratories, and compared them with those obtained using an established 1 H-qNMR method. 3,5-Bis(trifluoromethyl)benzoic acid (3,5-BTFMBA) was selected as the reference standard for both 19 F-qNMR and 1 H-qNMR owing to its solubility characteristics and 19 F-qNMR and 1 H-qNMR chemical shifts. Since VCZ contains three fluorines, the 19 F-qNMR spectrum of VCZ showed three major fluorine signals (FA, FB, and FC). 19 F-qNMR measurements were performed under three conditions with each 19 F signal of VCZ (FA, FB, and FC) and the 19 F signal of RS as the center (offset) of each observation. The quantitative values of the three target signals FA, FB, and FC were calculated and were comparable; 99.40 %, 99.66 %, and 99.49 %, respectively. Owing to a difference of up to 8.8 % between the quantitative values of the two signals other than the targeted quantitative signal, the average FA, FB, and FC quantitative values were considered for purity (%). The purity of VCZ determined by 1 H- and 19 F-qNMR was comparable (99.65±0.29 % and 99.52±0.44 %, respectively), exhibiting variations within an acceptable range. Compared to conventional 1 H-qNMR methods, the developed 19 F-qNMR method has been proven efficient and highly promising for determining the accurate purity of organic fluorine pharmaceuticals.
Authors: Nahoko Uchiyama, Junko Hosoe, Kohei Kiyota, Takanori Komatsu, Naoki Sugimoto, Kyoko Ishizuki, Tatsuo Koide, Mika Murabayashi, Taeko Shinozaki, Yoshinori Fujimine, Katsuya Ofuji, Hitoshi Shimizu, Kazuhiro Fujita, Takashi Hasebe, Yumi Asai, Eri Ena, Yoshinobu Makino, Toru Miura, Yasuhiro Muto, Katsuo Asakura, Takako Suematsu, Hitomi Abe, Ai Kohama, Takashi Goto, Masu Yasuda, Tomohiko Ueda, Yukihiro Goda
Language: English
Subfield: Analytical Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $1,500
Awards: G2247173229, G4510494343
OpenAlex ID: W4402035612