目的 建立同時測定注射用唑來膦酸中雜質(zhì)B、C、D的HPLC法。方法 采用Titank Phenyl-Hexyl色譜柱（250 mm×4.6 mm，5 μm），以8 mg·mL^-1的1-辛烷磺酸鈉和0.037 mg·mL^-1的EDTA-二鈉為緩沖液，乙腈-緩沖液（4∶96）為流動相，體積流量0.8 mL·min^-1，柱溫20℃，檢測波長為215 nm，進樣量為10 μL。結(jié)果 在該色譜條件下，雜質(zhì)B、C、D之間的色譜峰分離度良好；各雜質(zhì)的檢測限和定量限分別為126.0～454.5 ng·mL^-1、315.0～1515.0 ng·mL^-1；各雜質(zhì)在相應(yīng)濃度范圍內(nèi)線性關(guān)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批注射用唑來膦酸樣品檢測結(jié)果顯示，雜質(zhì)B、C、D的質(zhì)量分?jǐn)?shù)均低于0.5%。結(jié)論 該方法簡便、靈敏、專屬性好，適用于注射用唑來膦酸中有關(guān)物質(zhì)的測定。

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

江蘇省產(chǎn)教融合一流課程《藥物分析》建設(shè)項目；江蘇海洋大學(xué)專業(yè)學(xué)位研究生課程《藥品質(zhì)量控制》案例庫建設(shè)項目（YJSZY202102）；江蘇海洋大學(xué)2023年一流課程《藥物儀器分析》建設(shè)項目；連云港市政策引導(dǎo)產(chǎn)學(xué)研項目（CYX2202）