目的 对羟苯甲酯和羟苯甲酯钠对照品的包装、贮存及使用风险进行评价研究。方法 采用多种方法联合分析，通过动态水分吸附分析法测定羟苯甲酯和羟苯甲酯钠的水分吸附动力学曲线和吸附/解吸附等温线，并与传统的引湿性试验结果相对比；通过费休氏容量滴定法测定并比较包装前后羟苯甲酯钠的水分含量和均匀性，干燥失重法测定包装前后羟苯甲酯的减失质量，考察了西林瓶和安瓿瓶两种包装用瓶的适用性；分别采用高效液相色谱（HPLC）法、粉末X射线衍射法、热重分析法和差示扫描量热分析法研究了羟苯甲酯和羟苯甲酯钠的化学稳定性、晶型稳定性以及热稳定性。结果 羟苯甲酯钠对照品置于温度25℃、相对湿度80%恒温恒湿箱内24 h，增重百分率为21.2%，极具引湿性；采用西林瓶或安瓿瓶包装均无法保证对照品量值的准确；引湿增重21.2%未对其HPLC纯度产生影响，但晶型发生了转变；热重分析表明，随着温度升高，样品中的水分完全释放。羟苯甲酯对照品无引湿性，西林瓶包装足以保证其量值的准确；长期贮存稳定，干燥不会对其稳定性产生影响，引湿前后未发生晶型转变。结论 通过对羟苯甲酯和羟苯甲酯钠对照品深入系统的研究，评价了对照品使用的关键点及风险级别，建议质量标准中采用羟苯甲酯对照品替代羟苯甲酯钠对照品。

Objective To evaluate the packaging, storage and use risk of methylparaben (MeP) and sodium methyl parahydroxybenzoate (SMeP) reference standards (RS). Methods Using a combination of methods, dynamic vapor sorption analysis was used to determine the moisture sorption dynamic curve and adsorption-desorption isotherm of MeP and SMeP, and compared with the results of traditional hygroscopicity test. The applicability of penicillin bottles and ampoule bottles were investigated by measuring and comparing the moisture content and uniformity of SMeP before and after packaging determined by the Karl fischer reaction method, and measuring the weight loss of MeP before and after packaging determined by loss on drying method. The chemical stability, crystal stability and thermal stability of MeP and SMeP were studied by HPLC, powder X-ray diffraction, thermogravimetry and differential scanning calorimetry. Results The weight gain of SMeP control sample was 21.2% in a constant temperature and humidity box with 25℃ and 80% relative humidity for 24 h, which was extremely hygroscopic; the accuracy of the weight gain of the control sample could not be guaranteed by using vials or ampoules; 21.2% of the weight gain of the control sample had no effect on the purity of HPLC, but the crystal type changed; TGA showed that the water in the sample was completely released with the increase of temperature. There is no hygroscopic property for the MeP reference product, and the packaging of Xilin bottle is enough to ensure the accuracy of its quantity value; the long-term storage was stable, and the drying will not affect its stability, and there was no crystal transformation before and after hygroscopic. Conclusion The key points and risk levels of MeP and SMeP RS were evaluated, which provided the basis for the revision of the quality standard.It is suggested that the reference of SMeP should be replaced by the reference of MeP in the quality standard.

R927.11

国家药典委员会药品标准制修订研究课题（2019Y16）；国家重大研发项目（2016YFE0205400）；化学药品质量研究与评价重点实验室项目