缬沙坦美托拉宗片溶出度检测的方法学研究

Methodological validation of the dissolution test of valsartan and metolazone tablets

目的建立缬沙坦美托拉宗片溶出度测定方法,并进行方法学验证,为药品的质量控制提供保障。方法采用高效液相色谱法,色谱柱为Agilent SB C18（4.6 mm×250 mm,5μm）色谱柱,流动相为乙腈-水（磷酸调p H值至2.3,比例50∶50）,流速1.0 ml/min,检测波长235 nm。结果缬沙坦在6~120μg/ml浓度范围内线性关系良好（r=1.0000,n=6）,美托拉宗在37.5~750 ng/ml浓度范围内线性关系良好（r=1.0000,n=6）;缬沙坦和美托拉宗的平均回收率分别为99.85%和99.44%,RSD分别为1.05%和1.16%,溶液在24 h内稳定,滤膜对两种药物均没有吸附,两种药物的重复性及中间精密度的相对标准偏差（RSD）均〈2%。结论建立的溶出度检测方法操作简单,灵敏度及准确度高,满足缬沙坦美托拉宗片质量控制的要求。

Objective To establish a method for testing the dissolution of valsartan and metolazone tablets,and validate the method to provide a basis for drug quality control. Methods The dissolution was analyzed by HPLC method. An Agilent SB C18（4.6mm×250 mm,5 μm）column and a mixture of acetonitrile and water were used with the ratio of 50∶50 at a flow rate of 1.0 ml/min with UV detection at 235 nm. Results The calibration curve of valsartan and metolazone was 6-120 μg/ml（r=1.0000,n=6）and 37.5-750ng/ml（r=1.0000,n=6）,respectively. The average recovery of the two drugs was 99.85% and 99.44% with RSD of 1.05% and 1.16%（n=9）,respectively.The test solution was stable within 24 h and the filter did not interfere with determination as the two drugs were not adsorbed on it.RSD of this method were all less than 2%. Conclusion The method is simple,sensitive,accurate,and with highly distinguished ability for quality control.