Validated quantitative 19F-NMR technique for the determination of ticagrelor: A novel method for fluorochemicals detection

Abstract

Accurate, simple and reproducible quantitative fluorine nuclear magnetic resonance spectroscopy (19F-NMR) method for the determination of ticagrelor was developed and validated. Some proton signals of ticagrelor in the low field split into multiple or became broad peaks for the coupling of fluorine atom, which complicates the analysis using routinely 1H NMR method. However, this phenomenon did not occur to 19F signals and 19F-NMR method was successfully applied to the content determination of ticagrelor with ciprofloxacin as internal standard (IS) in 0.5 mL mixed solutions of deuterated dimethylsulfoxide (DMSO‑d6), deuteroxide (D2O) and dimethylsulfoxide (DMSO) (1.5:1.5:2, v/v/v). 1H NMR method was also adopted to the content determination to clarify whether the multiple or broad peaks had influences on the results or not. Statistical F-test and student t-test at 95% confidence level were performed and results revealed that there were insignificant differences in terms of precision and average content between 19F-NMR and 1H NMR methods, demonstrating that both 19F-NMR and 1H NMR methods were suitable to the determination of ticagrelor so long as parameters were optimized.