盐酸地巴唑片质量分析研究

Quality Analysis of Bendazol Hydrochloride Tablets

目的探讨盐酸地巴唑片的质量现状及存在的问题。方法按现行质量标准[WS1-24(B)-89]对抽验样品进行法定检验;建立以下探索性研究方法:模拟处方工艺考察盐酸地巴唑片表面色斑的来源;采用超高效液相色谱-飞行质谱联用(UPLC-QTOF-MS)法和核磁共振波谱(NMR)法鉴定杂质;采用紫外-可见分光光度(UV)法测定不同溶出介质、不同厂家产品的溶出度,并计算不同批次产品的含量均匀度;建立测定样品含量的高效液相色谱(HPLC)法。结果法定检验中,183批次样品的合格率为53.55%;探索性研究中,样品表面的色点可能由辅料引入或压片机缺乏及时保养维护导致;最大未知杂质为2-(羟基苯基)苯并咪唑;样品在pH 5.8和pH6.8的磷酸盐缓冲液中溶解度较低,在pH 1.0盐酸溶液中的溶出行为相似;9批次样品含量均匀度的A+2.2 S值>15.0;建立的HLPC法测定结果与高氯酸滴定法比较无显著性差异(P>0.05)。结论盐酸地巴唑片总体质量水平一般,其现行质量标准的有效性和安全性指标设立不足,不能完全有效控制药品质量,需尽快提高质量标准。

Objective To evaluate the status and existing problems of the quality of Bendazol Hydrochloride Tablets.Methods The samples were examined by the statutory testing methods according to the current quality standard[WS1-24(B)-89].The following exploratory research methods were established:the source of color spots on the surface of Bendazol Hydrochloride Tablets was investigated by simulating the formulation process,the impurities were identified by the ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-QTOF-MS)and nuclear magnetic resonance(NMR),the dissolution profile of different dissolution media and products from different manufacturers was determined by the ultraviolet visible spectrophotometry(UV),the content uniformity of different batches of products was calculated,and a high-performance liquid chromatography(HPLC)method was established for the content determination of the samples.Results The statutory test results showed that the qualified rate of 183 batches of samples was 53.55%.The exploratory research results showed that the color spots on the surface of the samples might be caused by the introduction of excipients or the lack of timely maintenance of the tablet press machine,the largest unknown impurity was 2-(hydroxyphenylmethyl)benzimidazole,the solubility of the sample in p H 5.8 and p H 6.8 phosphate buffer was low,while the dissolution behavior of the samples in the pH 1.0 hydrochloric acid solution was similar,and the content uniformity item A+2.2 S value of nine batches of samples was higher than 15.0.There was no significant difference in the results determined by the established HLPC method and perchloric acid titration method.Conclusion The overall quality level of Bendazol Hydrochloride Tablets is general,the effectiveness and safety indicators of the current quality standard are insufficiently established,which can not fully and effectively control the quality of the drug,so it is necessary to improve the quality standard as soon as possible.