抗新型冠状病毒肺炎候选药物利托那韦首批国家对照品研制  

Development of the first national reference substance of ritonavir as a candidate drug against COVID-19

作　　者：熊婧[1] 刘毅[1] 刘朝霞[1] 李婕[1] 张才煜[1] 武香香[2] 何兰[1] XIONG Jing;LIU Yi;LIU Zhaoxia;LI Jie;ZHANG Caiyu;WU Xiangxiang;HE Lan(National Institutes for Food and Drug Control,NMPA Key Laboratory for Quality Research and Evaluation of Chemical Drugs,Beijing 102629,China;Henan University of Traditional Chinese Medicine,Academy of Chinese Medicine Sciences,Zhengzhou Henan 450046,China)

机构地区：[1]中国食品药品检定研究院,化学药品质量研究与评价重点实验室,北京102629 [2]河南中医药大学,中医药科学院,河南郑州450046

出　　处：《中国药物警戒》2022年第2期137-141,共5页Chinese Journal of Pharmacovigilance

基　　金：国家重点研发计划(2016YFE0205400);国家自然基金青年科学基金项目(21801020)。

摘　　要：目的研制供含量测定用的利托那韦首批国家化学对照品。方法采用红外光谱、质谱和核磁共振谱进行结构确证,使用2种高效液相色谱法(HPLC)进行有关物质分析,用面积归一化法、主成分自身对照法和外标法加响应因子计算HPLC纯度,采用多种分析方法对均匀性、稳定性及其他理化性质进行考察,应用质量平衡法计算含量,并通过核磁共振定量法和差示扫描量热法对含量结果的准确性进行验证。结果确证了利托那韦首批国家对照品的结构,并测定其含量为99.8%。结论利托那韦首批供含量测定用化学对照品的研制,可满足利托那韦原料、制剂及复方制剂的生产需要。Objective To establish the first national reference standard for determination of the content of ritonavir. Methods The structure of ritonavir was identified by means of IR, MS, ^(1)H-NMR and ^(13)C-NMR. HPLC purity was calculated via peak area normalization, principal component self-comparison, external standard methods and response factors. The homogeneity, stability and other physicochemical properties were investigated using various analytical methods. The content was determined using the mass balance method and verified by the NMR quantitative method and differential scanning calorimeter. Results The structure of the first national reference substance of ritonavir was confirmed and its content was determined to be 99.8%. Conclusion The development of the first national reference substance of ritonavir can meet the production needs of raw materials, preparations and compound preparations of ritonavir.

关 键 词：利托那韦 新型冠状病毒肺炎 对照品 标准物质 质量平衡法 核磁共振定量 动态蒸气吸附法 

分 类 号：R969.4[医药卫生—药理学]