依替膦酸钠及其有关物质的反相离子对色谱分析

An Assay of Etidronate and Its Related Metabolites by Ion-pair RP-HPLC

建立用于依替膦酸钠含量测定及有关物质检查的分析方法.采用反相离子对高效液相色谱法,蒸发光散射检测器检测.以Hypersil C8 BDS柱为固定相,流动相为甲醇-含8 mmol/L正戊胺的5 mmol/L乙酸铵缓冲液(用乙酸调节pH至7.0)(体积比为5:95),流速为1.0mL/min,柱温为室温.方法的线性范围为110～994μg/mL,回归方程为lg A=2.105lg ρ+1.972(r=0.999 9).方法的回收率为99%～102%,RSD为0.70%(n=9).在该色谱条件下,依替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.本法不需特殊的样品处理过程,快速,特异性好,适用于依替膦酸钠的常规检测,为该药的质量控制提供了新的可靠的分析手段.

An analytical method for determination of etidronate and related metabolites was developed,based on ion-pair reverse-phase high performance liquid chromatography(ion-pair RP-HPLC)coupled withevapora-tive light-scattering detection(ELSD).The ion-pair RP-HPLC was performed on a BDS C 8 column(5μm,4.6mm×150mm)atroomtemperature,usingthe mobile phase of methanol buffer solution(5mmol/Lammo-nium acetate and8mmol/L amylamine,adjusted to pH7.0with acetic acid)(5∶95by volume),at a flow rate of1.0mL/min.The linearity range was110-994μg/mL(r=0.9999,n=5).The recovery was99%-102%with RSD of0.70%(n=9).The active ingredient etidronate was successfully separated fromits related metabolites,includingresidual phosphoric acid duringthe synthesis ofetidronate and other pos-sible impurities from oxidation and decomposition such as phosphate.The method was rapid,simple,accu-rate and reproducible.Itwas successfullyemployed for the assay of etidronate in bulk material and pharmaceu-tical dosage form,as well as for the determination of its related metabolites.It provides a new and reliable means for quality control of etidronate.