目的建立匹伐他汀钙片溶出度测定方法，评价国内仿制药与原研药溶出曲线的相似性。方法建立高效液相色谱（HPLC）法测定匹伐他汀钙片含量，并进行专属性、回收率、精密度、重复性、稳定性等方法学考察。以原研药为参比制剂，采用桨法，转速50 r/min，测定仿制药与原研药在4种不同pH溶出介质（pH 1.2盐酸溶液、pH 4.5醋酸盐缓冲液、pH 6.8磷酸盐缓冲液、水）中的溶出度，绘制溶出曲线，采用相似因子（f₂）法分析溶出曲线相似性。结果色谱条件为：色谱柱Diamonsil C₁₈（250 mm×4.6 mm，5 μm），醋酸盐缓冲液（冰醋酸500 μL、醋酸铵140.6 mg，加水至1 000 mL）-乙腈（15：85）为流动相，波长244 nm。方法学验证结果均符合检测要求。其中3家仿制药与原研药溶出行为基本一致，另外1家仿制药在水和pH 4.5醋酸盐缓冲液中均与原研药溶出曲线不相似。结论大部分厂家仿制药体外溶出与原研药一致。所建HPLC法适用于匹伐他汀钙片的浓度测定，可为今后匹伐他汀钙片溶出度一致性评价提供参考。

Objective To establish a method for determination of dissolution curve of pivastatin calcium tablets, and evaluate the similarity of dissolution curve of domestic generic drugs and the original drugs. Methods The concentrations of samples were detected by HPLC. The specificity, recovery, precision, repeatability, stability and other methodological studies were carried out. The paddle method was using for the dissolution process. The rotation speed of paddle was 50 r/min. To determine the dissolution profiles of generic pivastatin calcium tablets and the original product in four dissolution mediums (the pH 1.2 hydrochloric acid solution, the pH 4.5 acetate buffer solution, the pH 6.8 phosphate buffer solution and water). The f₂ factor method was used for analyze the similarity of dissolution curves. Results A Diamonsil C₁₈ column (250 mm×4.6 mm, 5 μm) was used. Mobile phase consisted of a mixture of acetate buffer(acetic acid 500 μL and ammonium acetate 140.6 mg were added to 1 000 mL water)-acetonitrile(15: 85), and UV detection wavelength was 244 nm. The results of methodology validation met the detection requirements. The dissolution profile of three generic tablet were similar to the original tablet in the four dissolution media. The dissolution of the other company's products was inconformity to the innovater drug in the water dissolution media and pH 4.5 acetate buffer solution. Conclusion The in vitro dissolution of some generic drugs was significantly different from the original drug. The HPLC method be appropriate for the determination of the concentration of pivastatin calcium tablets, which can provide a reference for further consistency evaluation of pivastatin calcium tablets.

R927

河北省卫健委医学科学研究课题计划（20200916）