复方地巴唑氢氯噻嗪胶囊中盐酸异丙嗪和氯氮的有关物质分析

目的:建立测定复方地巴唑氢氯噻嗪胶囊中盐酸异丙嗪和氯氮产生的有关物质。方法:采用高效液相色谱法。色谱柱为ZORBAX SB-C8,流动相为0.05 mol/L磷酸二氢铵(p H 3.2)-甲醇(梯度洗脱),检测波长为254 nm;按照对照品保留时间归属各杂质及采用液质联用法确定氯氮中的杂质,面积归一化法计算51批10个企业样品中有关物质的量。结果:主成分与有关物质能有效分离,且空白辅料和其他组分对检测成分未见干扰,盐酸氯丙嗪和氯氮中杂质检测限分别为2.5、2 ng;51批次样品检查结果显示盐酸异丙嗪的杂质量较低(均低于1%),而氯氮的杂质量普遍较高(大多在2%⁵%),且后者中的主要杂质为7-氯-5-苯基-1,3-二氢-1,4-苯并二氮杂-2-酮(4-氧化物)。结论:本方法可用于分析复方地巴唑氢氯噻嗪胶囊中盐酸异丙嗪和氯氮产生的有关物质。

Analysis of Related Substances Produced by Promethazine Hydrochloride and Chlordiazepoxide in Compound Bendazol and Hydrochlorothiazide Capsules

OBJECTIVE：To establish a method for the detection of related substance produced by promethazine hydrochloride and chlordiazepoxide in Compound bendazol and hydrochlorothiazide capsules. METHODS：HPLC method was adopted. The determination was performed on ZORBAX SB-C8 column with mobile phase consisted of 0.05 mol/L ammonium dihydrogen phosphate（p H 3.2）-methanol（gradient elution）. The detection wavelength was set at 254 nm. According to the retention time of substance control,LC-MS method was adopted to determine the impurity of chlordiazepoxide,and the amount of related substance in 51 batches of samples from 10 manufacturers were calculated by normalization method of peak area. RESULTS：Main component was separated from related substance,and test component didn＇t suffered from the interference from blank exicipients and other component. The detection limits of impurity in promethazine hydrochloride and chlordiazepoxide were 2.5 ng and 2 ng. 51 batches of samples showed that the amount of impurities by promethazine hydrochloride was in low level（less than 1%）,and that of chlordiazepoxide was generally high（mostly between 2%-5%）. The impurity of the latter was 7-chloro-5-phenyl-1,3-2 hydro-1,4 benzodiazepine-2-ketone（4-oxide）. CONCLUSIONS：This method could be used for detecting the related substances produced by promethazine hydrochloride and chlordiazepoxide in Compound bendazol and hydrochlorothiazide capsules.