HPLC-MS法测定奈玛特韦原料药3个非对映异构体  

Determination of three diastereoisomers in nirmatrelvir API by HPLC-MS

作　　者：金云 张显华 王俊 李金霞 吴耀莉 沈梦洁 赵龙山[1] JIN Yun;ZHANG Xian-hua;WANG Jun;LI Jin-xia;WU Yao-li;SHEN Meng-jie;ZHAO Long-shan(College of Pharmaceutical Sciences,Shenyang Pharmaceutical University,Shenyang 110016,China;Zhejiang Huahai Pharmaceuticals Co.,Ltd.,Linhai 317024,China;Agilent Technologies(China)Ltd.,Inc.,Beijing 100102,China)

机构地区：[1]沈阳药科大学药学院,沈阳110016 [2]浙江华海药业股份有限公司,临海317024 [3]安捷伦科技(中国)有限公司,北京100102

出　　处：《药物分析杂志》2025年第1期175-180,共6页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立HPLC-MS法检测奈玛特韦原料药3个非对映异构体。方法:采用InfinityLab Poroshell SB-C_(18)(150 mm×3.0 mm,2.7μm)色谱柱,2根串联使用,以缓冲液(0.1%甲酸溶液)(A)-乙腈(B)为流动相,以水-乙腈-甲醇(61∶19.5∶19.5)为稀释液,进行梯度洗脱,柱温80℃,进样量2μL,样品温度5℃,以电喷雾离子(ESI+)作为离子源,SIM模式扫描。结果:奈玛特韦与3个非对映异构体能够完全分离(分离度>1.5),供试品溶液在3 d内稳定性良好;非对映异构体1的定量限为0.04%,非对映异构体2的定量限为0.04%,非对映异构体3的定量限为0.05%;非对映异构体3线性相关系数>0.99,范围为杂质定量限浓度~150%指标浓度;非对映异构体3平均回收率(n=9)为97.2%,RSD为3.1%;重复性和中间精密度符合规定。经检测,3批奈玛特韦原料药24个月长期稳定性3个非对映异构体结果均符合质量标准。结论:该方法简便快速,灵敏度高,专属性强,可用于奈玛特韦原料药3个非对映异构体的测定。Objective:To establish an HPLC-MS method for determination of three diastereoisomers in nirmatrelvir API.Methods:The analytical column was an InfinityLab Poroshell SB-C_(18)(150 mm×3.0 mm,2.7μm),the two columns connected in series in series.The mobile phase was buffer(0.1%formic acid)(A)-acetonitrile(B),the diluent was water-acetonitrile-methanol(61∶19.5∶19.5).The whole run carried out by gradient elution.The column temperature was 80℃,the injection volume was 2μL,and the sample temperature was 5℃.Results:Nirmatrelvir was separated completely from three diastereoisomers(the resolution>1.5).The test solution was stable for at least 3 d.The LOQ of diastereoisomer 1 was 0.04%,the LOQ of diastereoisomer 2 was 0.04%,the LOQ of diastereoisomer 3 was 0.05%.The linear correlation coefficient of diastereoisomer 3 was>0.99.The linear range was LOQ-150%of specification.The average recovery(n=9)of diastereoisomer 3 was 97.2%,RSD=3.1%.The repeatability and intermediate precision completely met the requirements.The three diastereoisomers contents in three batches of nirmatrelvir API 24 months long-term stability test were all completely met the requirements,respectively.Conclusion:This method is simple,rapid,sensitive and specific to be used for the determination of three diastereoisomers in nirmatrelvir API.

关 键 词：奈玛特韦 奈玛特韦原料药 非对映异构体 高效液相色谱联合质谱法 质量控制 分析方法开发 分离 

分 类 号：R917[医药卫生—药物分析学]