目的 對(duì)國(guó)產(chǎn)勞拉西泮片的關(guān)鍵質(zhì)量屬性進(jìn)行分析，為該品種現(xiàn)行質(zhì)量標(biāo)準(zhǔn)的完善以及質(zhì)量風(fēng)險(xiǎn)控制提供依據(jù)。方法 在了解國(guó)內(nèi)勞拉西泮片整體質(zhì)量狀況的基礎(chǔ)上，以問(wèn)題為導(dǎo)向，圍繞安全性和有效性，選擇片劑的有關(guān)物質(zhì)、溶出度等質(zhì)控關(guān)鍵點(diǎn)開(kāi)展研究。結(jié)果 通過(guò)對(duì)原料雜質(zhì)譜的分析，確認(rèn)USP雜質(zhì)C（ChP雜質(zhì)Ⅱ）為勞拉西泮最主要的降解雜質(zhì)，同時(shí)確定了該雜質(zhì)的來(lái)源；ChP現(xiàn)行標(biāo)準(zhǔn)有關(guān)物質(zhì)檢查方法能夠有效分離已知及未知雜質(zhì)，且雜質(zhì)的定量方法合理；斑馬魚(yú)胚胎發(fā)育毒性結(jié)果顯示雜質(zhì)C的神經(jīng)毒性較勞拉西泮強(qiáng)；對(duì)現(xiàn)行標(biāo)準(zhǔn)溶出度檢查法進(jìn)行了優(yōu)化；國(guó)產(chǎn)制劑與進(jìn)口制劑在體外溶出特性方面存在一定差別。結(jié)論 國(guó)產(chǎn)勞拉西泮片的整體質(zhì)量狀況良好，但與進(jìn)口制劑間仍存在一定的差距，應(yīng)提高生產(chǎn)工藝的穩(wěn)定性?，F(xiàn)行標(biāo)準(zhǔn)基本上能夠?qū)崿F(xiàn)對(duì)本品關(guān)鍵指標(biāo)的控制，但溶出度檢查項(xiàng)有待優(yōu)化，以提高對(duì)不同質(zhì)量產(chǎn)品的區(qū)分度。

Objective The critical quality attributes of domestic Lorazepam tablets were analyzed, in order to improve the current quality standard and provide direct ground for quality risk control. Methods On the basis of evaluating the whole quality status of domestic Lorazepam tablets, several exploratory researches were carried out using problem-oriented approach. It involved in the related substances and dissolution. Results By investigation of the impurity profile, Lorazepam related compound C was considered to be the critical impurity of Lorazepam, and the source and the degradation pathway were discussed. The current quality standard can effectively separate the known and the unknown impurities, and the quantitative methods for impurities were rational. Moreover, the effect of Lorazepam and its related compound B and C on cell proliferation has no significant difference, but the toxicity of Lorazepam related compound C on zebrafish embryos were strongest than that of Lorazepam and related compound B. The method of dissolution was optimized and it was found that there were some differences between domestic and imported preparations in dissolution characteristics in vitro. Conclusion The overall quality of domestic Lorazepam tablets was satisfied, but there was still the certain gap between domestic and imported preparations. The stability of production process should be improved, and it was suggested to optimize the dissolution test to improve the differentiation of different quality products.