离子对反相高效液相色谱法测定阿仑膦酸钠含量及其有关物质

Determination of Alendronate and Its Related Substances by Ion-pair Reversed Phase-High Performance Liquid Chromatography

以挥发性的正戊胺作为离子对试剂,采用离子对反相高效液相色谱法,配以蒸发光散射检测器（ELSD）检测,建立了用于阿仑膦酸钠含量测定及相关物质检查的分析方法.以Iintersil C8 柱为固定相,流动相为50 mmol/L正戊胺水溶液（用乙酸调节pH至7.0）-甲醇（98： 2）,流速为1.0 mL/min,柱温为室温.方法的线性范围为200～1000 mg/L;回归方程为lgA=2.5884lgC-0.243,r=0.9990;方法的平均回收率为100.4%;RSD为0.65%.在该色谱条件下,阿仑膦酸钠与其有关物质（包括残留的合成原料亚磷酸及氧化分解产物磷酸盐）的分离良好,且样品测定不受辅料干扰.样品测定结果满意.本法不需特殊的样品处理过程,快速,特异性好,适用于阿仑膦酸钠的常规检测及有关物质检查,为该药的质量控制提供了可靠的分析手段.

An isocratic liquid chromatographic method with evaporative light scattering detection （ELSD） was developed for analysis of alendronate and its related substances which are not retained on non-polar column and lack chromophore for detection. Volatile n-amylamine was used as ion-pairing agent. Separations were performed on an Inertsil Cs column （4.6 mm × 150 mm, 5 μm） with a mobile phase of 50 mmol/L amylamine aqueous solution （adjusted to pH 7.0 with acetic acid）-methanol （98： 2）. The flow rate was 1.0 mL/min. The linearity range was 200 - 1000 mg/L （r =0. 9990, n =5）. The average recovery was 100.4% with RSD of 0.7%. The active ingredient-alendronate was successfully separated from its related substances, including remained phosphoric acid in the synthesis of alendronate and other possible impurities of oxidation and decomposition such as phosphate. The method is rapid, simple, accurate and reproducible and provides a new and reliable means for the quality control of alendronate.