目的 建立測定唑來膦酸原料藥及粉針劑中主成分唑來膦酸含量的HPLC法。方法 采用Kromasil 100-5-C₁₈ （250 mm×4.6 mm，5 μm）色譜柱，制備0.2%的三乙胺溶液、用磷酸調(diào)pH至4.0作為緩沖液，乙腈-緩沖液（4∶96）為流動相，體積流量為0.8 mL·min^-1，檢測波長為215 nm，柱溫為25℃，進樣量10 μL。結(jié)果 唑來膦酸與相鄰峰的分離效果良好，分離度為3.9，主成分唑來膦酸在100.2～1 002.0 μg·mL^-1線性關(guān)系良好，R²為0.998 6，檢測限和定量限分別為75.2、250.5 ng·mL^-1，回收率在105.2%～111.4%，重復性試驗、中間精密度試驗、穩(wěn)定性、耐用性符合要求。3批原料藥和粉針劑的檢測結(jié)果顯示，唑來膦酸的質(zhì)量分數(shù)均≥95.0%。結(jié)論 經(jīng)方法學驗證，所建立方法靈敏、高效、專屬性強、準確度高，可作為測定唑來膦酸原料藥及粉針劑主成分唑來膦酸含量的方法。

Objective An HPLC method was developed for the simultaneous determination of zoledronic acid in API and powder formulations. Method A Kromasil 100-5-C₁₈ (250 mm × 4.6 mm, 5 μm) column was used for the quantitative analysis of the main components. The mobile phase was acetonitrile-triethylamine solution (4:96), pH adjusted to 4.0 with phosphoric acid, at a flow rate of 0.8 mL·min^-1, detection wavelength of 215 nm, column temperature of 25 ℃ and injection volume of 10 μL. Results The separation of zoledronic acid from the surrounding peaks was good, the degree of separation is 3.9. The linear range of the principal component zoledronic acid was good from 100.2 to 1 002.0 μg·mL^-1 with the correlation coefficients R² greater than 0.998 6. The limits of detection and limits of quantification of the principal component zoledronic acid were 75.2 and 250.5 ng·mL^-1, respectively. The recoveries of the main ingredient zoledronic acid were in the range of 105.1%-111.4% and repeatability test, intermediate precision test, stability and durability meet the requirements. The results of the three batches of API and powder injection showed that the content of the main ingredient zoledronic acid was higher than 95%. Conclusion The results of the methodological validation showed that the established method was proved to be sensitive, efficient, specific and accurate, and can be used as a method for determining the content of zoledronic acid API and powder injection.

R932

江蘇省產(chǎn)教融合一流課程《藥物分析》建設(shè)項目；江蘇海洋大學專業(yè)學位研究生課程案例庫建設(shè)項目（YJSZY202102）；江蘇海洋大學2023年一流課程《藥物儀器分析》建設(shè)項目；連云港市政策引導產(chǎn)學研項目（CYX2202）