目的 建立唑来膦酸原料药中杂质A、B、C、D的HPLC测定方法。方法 采用Titank Phenyl-Hexyl色谱柱（250 mm×4.6 mm，5 μm）对杂质A、B、C、D进行定量分析，以8 mg·mL^-1的1-辛烷磺酸钠和0.037 mg·mL^-1的EDTA-二钠为缓冲液，缓冲液-乙腈（4∶96）为流动相，进行等度洗脱，体积流量为0.8 mL·min^-1，检测波长为215 mm，柱温为20℃，进样量为10 μL。结果 空白溶液不干扰对各杂质的检测；各杂质在相应浓度范围内线性关系良好，R²均不小于0.990；各杂质的检测限分别为192.6、545.5、126.0、150.0 ng·mL^-1，定量限分别为629、1 515、315、500 ng·mL^-1；各杂质的平均回收率分别为95.4%、82.4%、92.0%、95.9%，RSD分别为2.8%、2.7%、2.9%、2.4%；3批样品有关物质的测定结果显示，各杂质的质量分数均低于0.3%。结论 方法学验证结果显示，建立的HPLC法适用于唑来膦酸原料药中杂质A、B、C、D的检测。

Objective To establish a HPLC method for the determination of impurities A, B, C and D in zoledronic acid. Methods A Titank Phenyl-Hexyl column (250 mm × 4.6 mm, 5 μm) was used for quantitative analysis of impurities A, B, C and D. Using 8 mg·mL^-1 sodium 1-octanesulfonic acid and 0.037 mg·mL^-1 EDTA-disodium as buffer, buffer with acetonitrile (4:96) as mobile phase. The elution was carried out at a volume flow rate of 0.8 mL·min^-1, the detection wavelength was 215 mm, the column temperature was 20 ℃, and the injection volume was 10 μL. Results The blank solution did not interfere with the detection of impurities. Each impurity had a good linear relationship in the corresponding concentration range, and the correlation coefficient R² was not less than 0.990. The detection limits of the impurities were 192.6, 545.5, 126.0 and 150.0 ng·mL^-1, respectively, and the limits of quantification were 629, 1 515, 315 and 500 ng·mL^-1, respectively. The average recovery rates of each impurity were 95.4%, 82.4%, 92.0% and 95.9%, respectively, and the RSD were 2.8%, 2.7%, 2.9% and 2.4%, respectively. The results of three batches of samples showed that the content of each impurity was less than 0.3%. Conclusion The method can be used to detect impurities A, B, C and D in zoledronic acid raw materials.

R932

江苏省产教融合一流课程《药物分析》建设项目；江苏海洋大学专业学位研究生课程《药品质量控制》案例库建设项目（YJSZY202102）；江苏海洋大学2023年一流课程《药物仪器分析》建设项目；连云港市政策引导产学研项目（CYX2202）