两种阿仑膦酸钠片的崩解度和溶出度及在Caco-2细胞模型上的转运比较

目的：建立9-氯甲酸芴甲酯（FMOC）柱前衍生化高效液相色谱法测定阿仑膦酸钠片含量的方法,比较两种阿仑膦酸钠片的崩解度、溶出度和转运特性,为该药物制剂开发和临床应用提供参考。方法：采用Kromasil-C18色谱柱（4.6mm×150mm,5μm）;以甲醇-乙腈-柠檬酸与焦磷酸钠混合液为流动相,梯度洗脱;流速为1mL·min-1;柱温为35℃;紫外检测波长为265nm。结果：阿仑膦酸钠在2-200μg·mL-1范围内线性关系良好（r=0.9998）,回收率、日内和日间精密度RSD均小于15%。两种阿仑膦酸钠片的崩解度、溶出度均有一定的差异,而在Caco-2细胞模型的转运量没有显著的差异。结论：两种阿仑膦酸钠片的生物利用度、药代动力学可能存在差异。

Comparison on disintegration, dissolution and transport across Caco-2 cell monolayer of two alendronate sodium tablets

Objective： To develop an HPLC method with 9-fluorenylmethyl chloroformate （FMOC） pre-column derivatization for determination of alendronate sodium tablets, and compare the disintegration, dissolution and transport of two alendronate sodium tablets to provide reference for the development and clinical application of alendronate sodium preparation. Methods： A Kromasil-C18 （4.6 mm×150 mm, 5 μm） was adopted as analytical column. The mobile phase consisted of methanol-acetonitrile-the mixture of citric acid and pyrophosphate sodium at a flow rate of 1 mL·min-1 with gradient elution. The column temperature was 35 ℃, and the UV detection wavelength was set at 265 nm. Results： The calibration curve of alendronate sodium was linear within the concentration range of 2 ~ 200 μg·mL-1 （r = 0.999 8）. The recovery, the intra-day RSD and the inter-day RSD were all less than 15%. There were differences in disintegration and dissolution between two alendronate sodium tablets, while there was no significant difference in terms of transport across Caco-2 cell model. Conclusion： The results of disintegration and dissolution suggested that there may be some differences between two alendronate sodium tablets with regard to bioavailability and pharmacokinetics.