目的 對(duì)羥苯甲酯和羥苯甲酯鈉對(duì)照品的包裝、貯存及使用風(fēng)險(xiǎn)進(jìn)行評(píng)價(jià)研究。方法 采用多種方法聯(lián)合分析，通過動(dòng)態(tài)水分吸附分析法測定羥苯甲酯和羥苯甲酯鈉的水分吸附動(dòng)力學(xué)曲線和吸附/解吸附等溫線，并與傳統(tǒng)的引濕性試驗(yàn)結(jié)果相對(duì)比；通過費(fèi)休氏容量滴定法測定并比較包裝前后羥苯甲酯鈉的水分含量和均勻性，干燥失重法測定包裝前后羥苯甲酯的減失質(zhì)量，考察了西林瓶和安瓿瓶兩種包裝用瓶的適用性；分別采用高效液相色譜（HPLC）法、粉末X射線衍射法、熱重分析法和差示掃描量熱分析法研究了羥苯甲酯和羥苯甲酯鈉的化學(xué)穩(wěn)定性、晶型穩(wěn)定性以及熱穩(wěn)定性。結(jié)果 羥苯甲酯鈉對(duì)照品置于溫度25℃、相對(duì)濕度80%恒溫恒濕箱內(nèi)24 h，增重百分率為21.2%，極具引濕性；采用西林瓶或安瓿瓶包裝均無法保證對(duì)照品量值的準(zhǔn)確；引濕增重21.2%未對(duì)其HPLC純度產(chǎn)生影響，但晶型發(fā)生了轉(zhuǎn)變；熱重分析表明，隨著溫度升高，樣品中的水分完全釋放。羥苯甲酯對(duì)照品無引濕性，西林瓶包裝足以保證其量值的準(zhǔn)確；長期貯存穩(wěn)定，干燥不會(huì)對(duì)其穩(wěn)定性產(chǎn)生影響，引濕前后未發(fā)生晶型轉(zhuǎn)變。結(jié)論 通過對(duì)羥苯甲酯和羥苯甲酯鈉對(duì)照品深入系統(tǒng)的研究，評(píng)價(jià)了對(duì)照品使用的關(guān)鍵點(diǎn)及風(fēng)險(xiǎn)級(jí)別，建議質(zhì)量標(biāo)準(zhǔn)中采用羥苯甲酯對(duì)照品替代羥苯甲酯鈉對(duì)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

國家藥典委員會(huì)藥品標(biāo)準(zhǔn)制修訂研究課題（2019Y16）；國家重大研發(fā)項(xiàng)目（2016YFE0205400）；化學(xué)藥品質(zhì)量研究與評(píng)價(jià)重點(diǎn)實(shí)驗(yàn)室項(xiàng)目