| Autor: |
Uchiyama N; National Institute of Health Sciences (NIHS)., Hosoe J; National Institute of Health Sciences (NIHS)., Komatsu T; JEOL Ltd., Sugimoto N; National Institute of Health Sciences (NIHS)., Ishizuki K; National Institute of Health Sciences (NIHS)., Koide T; National Institute of Health Sciences (NIHS)., Murabayashi M; Takeda Pharmaceutical Co., Ltd., Shinozaki T; Daiichi Sankyo Co., Ltd., Kobayashi K; Daiichi Sankyo Co., Ltd., Fujimine Y; Otsuka Pharmaceutical Co., Ltd., Ofuji K; Chugai Pharmaceutical Co., Ltd., Shimizu H; Chugai Pharmaceutical Co., Ltd., Hasebe T; Eisai Co., Ltd., Asai Y; Eisai Co., Ltd., Ena E; Eisai Co., Ltd., Kiyota K; Shionogi & Co., Ltd., Fujita K; Shionogi & Co., Ltd., Makino Y; Juzen Chemical Corp., Miura T; FUJIFILM Wako Pure Chemical Corporation., Muto Y; FUJIFILM Wako Pure Chemical Corporation., Asakura K; JEOL Ltd., Suematsu T; JEOL Ltd., Muto H; JEOL Ltd., Kohama A; Pharmaceutical and Medical Device Regulatory Science Society of Japan (PMRJ)., Goto T; Nippon Shinyaku Co., Ltd., Yasuda M; Nippon Shinyaku Co., Ltd., Ueda T; Sumitomo Pharma Co., Ltd., Goda Y; National Institute of Health Sciences (NIHS). |
| Abstrakt: |
The spectrum of 31 P-NMR is fundamentally simpler than that of 1 H-NMR; consequently identifying the target signal(s) for quantitation is simpler using quantitative 31 P-NMR ( 31 P-qNMR) than using quantitative 1 H-NMR ( 1 H-qNMR), which has been already established as an absolute determination method. We have previously reported a 31 P-qNMR method for the absolute determination of cyclophosphamide hydrate and sofosbuvir as water-soluble and water-insoluble organophosphorus compounds, respectively. This study introduces the purity determination of brigatinib (BR), an organophosphorus compound with limited water solubility, using 31 P-qNMR at multiple laboratories. Phosphonoacetic acid (PAA) and 1,4-BTMSB-d 4 were selected as the reference standards (RSs) for 31 P-qNMR and 1 H-qNMR, respectively. The qNMR solvents were chosen based on the solubilities of BR and the RSs for qNMR. CD 3 OH was selected as the solvent for 31 P-qNMR measurements to prevent the influence of deuterium exchange caused by the presence of exchangeable intramolecular protons of BR and PAA on the quantitative values, while CD 3 OD was the solvent of choice for the 1 H-qNMR measurements to prevent the influence of water signals and the exchangeable intramolecular protons of BR and PAA. The mean purity of BR determined by 31 P-qNMR was 97.94 ± 0.69%, which was in agreement with that determined by 1 H-qNMR (97.26 ± 0.71%), thus indicating the feasibility of purity determination of BR by 31 P-qNMR. Therefore, the findings of this study may provide an effective method that is simpler than conventional 1 H-qNMR for the determination of organophosphorus compounds. |
