作者：李星影1, 雍智全2, 任霞3, 王睿1, 付晓芸1, 熊小平1, 徐小平1
作者单位：1. 四川大学华西药学院，四川 成都 610041;
2. 广州安好医药科技有限公司，广东 广州 510700;
3. 山东瑞安药业有限公司，山东 济南 251499
关键词：DX1002;抗肿瘤;容量分析;高效液相色谱法;含量测定
摘要：
该文以有机弱酸正丁铵盐DX1002为对象，评价弱酸弱碱盐原料药的含量测定方法，优化出HPLC法为DX1002含量测定的最佳方法。根据DX1002的苯丙乙烯酸正丁铵盐的结构特点，分别针对本品的酸根部分、正丁铵离子部分和共轭体系部分等采用容量法（酸碱滴定和非水滴定）、紫外分光光谱法（UV）和高效液相色谱法（HPLC）进行含量测定，通过比较其精密度、回收率和含量结果，评价优选出最佳的方法。DX1002在4种方法分析中均具有良好的线性关系，重复性精密度RSD在0.063%~2.0%，平均加样回收率在99.4%~101.8%，平均含量99.3%~103.6%，其中非水滴定法和HPLC法的含量结果<100%，酸碱滴定法和光谱法的含量结果>100%。结果表明，4种定量方法没有显著性差异（P>0.05），但采用HPLC法可更好地克服供试样品中共存杂质的干扰，具有高专属、高灵敏和良好精密度等优点，建议可作为弱酸铵盐类化合物DX1002含量测定的较好方法。
Evaluation of the assay methods on a new anticancer drug of weak acid ammonium salt DX1002
LI Xingying1, YONG Zhiquan2, REN Xia3, WANG Rui1, FU Xiaoyun1, XIONG Xiaoping1, XU Xiaoping1
1. West China School of Pharmacy, Sichuan University, Chengdu 610041, China;
2. Guangzhou Anhao Pharmaceutical Technology Co., Ltd., Guangzhou 510700, China;
3. Shandong Ruian Pharmaceutical Co., Ltd., Jinan 251499, China
Abstract: To establish and optimize the determination methods of a weak acid ammonium salt DX1002. According to the structural characteristics of DX1002 including the acid radical part, n-butylammonium ion part, and conjugate system part, we respectively utilized volumetric methods (acid-base titration and non-aqueous titration), UV method and HPLC method to determine the content for this weak acid ammonium salt and select the best evaluation method by comparing the precision, recovery and content results. DX1002 has a good linear relationship of the four quantitative methods. The precision is good (RSD is 0.063%-2.0%). The average sample recovery is 99.4%-101.8% and the average content is 99.3%-103.6%. The results of non-aqueous titration and HPLC are less than 100%, the results of acid-base titration and spectrophotometry are more than 100%. The results show that the four quantitative methods have no significant difference (P > 0.05), but the interference of co-existing impurities in the samples can be overcome by HPLC, which have the advantages of high specificity, high sensitivity and good precision, it is suggested that DX1002 can be used as a better method for the determination of weak acid ammonium salt compound.
Keywords: DX1002;anti-cancer;titrimetric analysis;HPLC;assay determination
2020, 46(8):64-68,81 收稿日期: 2020-02-02;收到修改稿日期: 2020-04-24
基金项目: 广州高新技术创新创业领军人才基金（2020-1019）
作者简介: 李星影（1996-），女，四川成都市人，硕士研究生，专业方向为药物质量控制和药物代谢分析
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