目的 建立同时测定注射用唑来膦酸中杂质B、C、D的HPLC法。方法 采用Titank Phenyl-Hexyl色谱柱（250 mm×4.6 mm，5 μm），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，乙腈-缓冲液（4∶96）为流动相，体积流量0.8 mL·min^-1，柱温20℃，检测波长为215 nm，进样量为10 μL。结果 在该色谱条件下，杂质B、C、D之间的色谱峰分离度良好；各杂质的检测限和定量限分别为126.0～454.5 ng·mL^-1、315.0～1515.0 ng·mL^-1；各杂质在相应浓度范围内线性关系良好，R²在0.999 3～1.000 0；平均回收率在93.1%～102.5%，RSD均小于10.0%；且3批注射用唑来膦酸样品检测结果显示，杂质B、C、D的质量分数均低于0.5%。结论 该方法简便、灵敏、专属性好，适用于注射用唑来膦酸中有关物质的测定。

Objective An HPLC method was developed for the simultaneous determination of impurity B, impurity C and impurity D in Zoledronic Acid Injection. Methods The separation was performed on a Titank Phenyl-Hexyl column (250 mm × 4.6 mm, 5 μm) with 8 mg·mL^-1 sodium 1-octanesulfonate and 0.037 mg·mL^-1 EDTA-disodium as the buffer, acetonitrile-buffer (4:96) as the mobile phase, at a flow rate of 0.8 mL·min^-1, and the column temperature of 20 ℃, with a detection wavelength of 215 nm. The injection volume was 10 μL. Results Under these chromatographic conditions, the peaks between impurity B, impurity C and impurity D were well separated. The limits of detection and quantification of each impurity were 126.0 to 454.5 ng·mL^-1 and 315.0 to 1 515.0 ng·mL^-1, respectively. The linearity of each impurity in the corresponding concentration range was good, with R² in the range of 0.999 3 to 1.000 0, and the average recoveries were in the range of 93.1% to 102.5% with the RSDs less than 10.0%. The test results of three batches of Zoledronic Acid Injection showed that the contents of impurities B, C and D were all lower than 0.5%. Conclusion The method is simple, sensitive and specific, and is suitable for the determination of related substances in zoledronic acid for injection.

R932

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