氢氯噻嗪片中有关物质的测定及杂质结构推测  

Determination of Related Substances and Impurity Structure Estimation in Hydrochlorothiazide Tablets

作　　者：甘加明 黄莹[1] 黄诺哲 严全鸿[1] Gan Jiaming;Huang Ying;Huang Nuozhe;Yan Quanhong(Guangdong Institute for Drug Control,NMPA Key Laboratory for Rapid Testing Technology of Drugs,Guangzhou 510663,China)

机构地区：[1]广东省药品检验所,国家药品监督管理局药品快速检验技术重点实验室,广东广州510663

出　　处：《广东化工》2023年第23期113-117,共5页Guangdong Chemical Industry

基　　金：广东省医学科学技术研究基金项目(B2019109);广东省药品检验所基金项目(ZA20200020);广东省药品检验所基金项目(ZA20200017);广州市科学技术局基金项目(202102080640)。

摘　　要：目的:建立氢氯噻嗪片有关物质测定方法。方法:用十八烷基硅烷键合硅胶为填充剂,以0.5%甲酸溶液为流动相A,乙腈为流动相B,采用梯度洗脱程序,检测波长为275 nm,进样量10μL。结果:在选定的色谱条件下,空白辅料无干扰,各组分分离良好,杂质I和氯噻嗪分别在0.129~6.430μg·mL^(-1)(r=0.9999)、0.066~3.283μg·mL^(-1)(r=0.9999)浓度范围内线性关系良好;定量限分别为26.0、32.8 ng·mL^(-1),检测限分别为10.4、9.8 ng·mL^(-1);精密度的RSD均小于1.0%,平均回收率分别为99.4%(RSD=0.5%)、99.3%(RSD=0.6%)。测定的3个不同厂家生产的7批样品中,杂质I的含量为0.08%~0.28%,氯噻嗪的含量均为0.04%~0.05%,最大未知杂质含量为0.07%~0.13%,总杂质含量为0.21%~0.24%。采用二维液相-高分辨质谱仪,负离子扫描方式,分析样品中最大未知杂质和高温破坏产生的主要杂质。结论:该方法操作简便,专属性强,结果准确度高,优于现行标准方法,能有效反映药品质量,可作为氢氯噻嗪片的有关物质测定方法。Objective:To establish a method for the determination of related substances in hydrochlorothiazide tablets.Methods:octadecylsilane bonded silica gel was used as filler,0.5%formic acid solution was used as mobile phase A,acetonitrile was used as mobile phase B,gradient elution procedure,detection wavelength was 275nm,injection volume was 10μL.Results:under the selected chromatographic conditions,the blank excipients had no interference and the components were well separated.The linear ranges of impurity I,chlorthiazide and hydrochlorothiazide were 0.129~6.430μg·mL^(-1)(r=0.9999)and 0.066~3.283μg·mL^(-1)(r=0.9999),respectively;the limits of quantitation were 26.0 and 32.8 ng·ml-1,respectively The detection limits were 10.4 and 9.8 ng·mL^(-1),respectively.The RSDs of precision were less than 1.0%,and the average recoveries were 99.4%(RSD=0.5%)and 99.3%(RSD=0.6%),respectively.Among the 7 batches of samples produced by 3 different manufacturers,the content of impurity I was 0.08%~0.28%,the content of chlorothiazide was 0.04%~0.05%,the maximum unknown impurity content was 0.07%~0.13%,and the total impurities content is 0.21%~0.24%.The impurity composition was analyzed by two-dimensional liquid phase-high resolution mass spectrometry and negative ion scanning mode.The m/z of the main impurity produced by high temperature destruction was 283.9575 and the m/z of maximum unknown impurity was 604.9235.Conclusion:The method is simple,specific and accurate,which is superior to the current standard method.It can effectively reflect the quality of drugs and can be used as a method for the determination of related substances in hydrochlorothiazide tablets.

关 键 词：氢氯噻嗪 氯噻嗪 苯并噻二嗪 有关物质 

分 类 号：R927.2[医药卫生—药学]