¹⁹F_qNMR定量法测定五氟利多的含量

目的:采用¹⁹F核磁共振定量法(¹⁹F qNMR法)测定五氟利多的绝对含量。方法:以4-氟肉桂酸为内标,以二甲基亚砜为溶剂,采用Bruker Avance Ⅲ 400型核磁共振谱仪,脉冲序列zgfhigqn.2在恒温25℃下获取¹⁹F核磁共振谱(¹⁹F NMR谱),测定五氟利多的含量,驰豫延迟时间(D1)为10 s。结果:以五氟利多的峰(δ-117.4)及4-氟肉桂酸(δ-110.9)峰作为定量峰;同一样品连续测试5次,测得精密度RSD为0.34%;平行配制6份供试溶液,其结果的重复性RSD为0.38%;将样品与内标的NMR峰面积比对其质量比绘制标准曲线,五氟利多的线性范围为6.58~22.85 mg,相关系数为0.9999;定量限为4.06 mg。¹⁹F qNMR法测得样品的含量为99.89%,与质量平衡法结果99.96%基本一致。结论:经方法学验证,¹⁹F qNMR法可用于测定五氟利多的绝对含量。

Objective: To establish a ¹⁹F quantitative nuclear magnetic resonance (¹⁹F qNMR) approach for the determination of penfluridol. Methods: ¹⁹F nuclear magnetic resonance (¹⁹F NMR) spectra were obtained by using an Avance Ⅲ 400 spectrometer with zgfhigqn.2 pulse sequence at 25℃, the solvent was DMSO, and the internal standard was 4-fluorocinnamic acid, the relaxation delay time (D1) was 10 s. Results: The peaks of penfluridol (δ-117.4) and 4-fluorocinnamic acid (δ-110.9) were used for quantitation. The sample was characterized for 5 times and the precision RSD was 0.34%. Totally 6 samples were prepared in parallel and characterized, the repeatability RSD was 0.38%. Linear relationship between the peak area ratio and the weight ratio of sample to inner standard was obtained as the linearity of penfluridol ranged from 6.58 mg to 22.85 mg (r=0.999 9). The LOQ was 4.06 mg. The result determined by the method (99.89%) was consistent with the result by mass balance method (99.96%). Conclusion: The ¹⁹F qNMR method was used for the quantitative determination of penfluridol. It is indicated that ¹⁹F qNMR is an effective,reliable and economic method.

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