离子对色谱法检测阿德福韦酯中降解产物的含量

目的: 建立阿德福韦酯主要的降解产物阿德福韦单特戊酸甲酯、阿德福韦及其他杂质的检测方法。 方法: 采用Welch Materials XB-C₈柱(250 mm×4.6 mm,5 μm),以0.05 mol·L^-1的磷酸氢二钾和0.01 mol·L^-1四丁基硫酸氢铵缓冲溶液(磷酸调pH至3.0)-乙腈(65∶35)为流动相,检测波长为260 nm,流速为1.0 mL·min^-1。 结果: 阿德福韦酯主峰与临近杂质峰可达到基线分离,主要降解产物阿德福韦、阿德福韦单特戊酸甲酯及9-(2-二乙氧基膦酰甲氧基乙基)腺嘌呤分离度均在2.0以上。阿德福韦、阿德福韦单特戊酸甲酯及阿德福韦酯分别在0.109~21.8 μg·mL^-1、0.111~22.2 μg·mL^-1、0.105~21.0 μg·mL^-1的浓度范围内呈良好的线性;阿德福韦和阿德福韦单特戊酸甲酯的回收率分别为98.8%、99.7%。 结论: 该方法简便,准确,专属性好,可适用于阿德福韦酯的有关物质检查及质量控制。

Objective: To establish a method for the determination of main degradation products including mono-POM PMEA,adefovir and other impurities in adefovir dipivoxil. Methods: The Welch Materials XB-C₈ column (250 mm×4.6 mm,5 μm) was adopted with the mobile phase consisting of buffer solution-acetonitrile (65∶35),the buffer solution contained 50 mmol·L^-1 potassium phosphate dibasic and 10 mmol·L^-1 tetrabutylammonium hydrogen sulfate,and was adjusted to pH 3.0 with phosphate acid.The detection wavelength was 260 nm,and the flow rate was 1.0 mL·min^-1. Results: The baseline separation was achieved between the main peak of adefovir dipivoxil and the near peak of impurities,and the resolutions among the main degradation products (i.e.,adefovir,mono-POM PMEA and 9-[2-(diethyl-phosphonomethoxy)ethyl] adenine) were above 2.0.The good linearity was obtained over the range of 0.109-21.8 μg·mL^-1 for adefovir,0.111-22.2 μg·mL^-1 for mono-POM PMEA,and 0.105~21.0 μg·mL^-1 for adefovir dipivoxil.The average recoveries were 98.8% for adefovir and 99.7% for mono-POM PMEA,respectively. Conclusion: This method is simple,accurate,with well specificity,and can be applied to determination of the relative substances in adefovir dipivoxil and quality control.