琥珀酸美托洛尔中潜在的环氧乙烷类基因毒性杂质含量测定研究  

Determination of ethylene oxide genotoxic impurity in metoprolol succinate

作　　者：刘春亮 刘小琼 张磊 朱克旭 曹杰永 王晨[4] 许明哲[4] 张现化[5] LIU Chunliang;LIU Xiaoqiong;ZHANG Lei;ZHU Kexu;CAO Jieyong;WANG Chen;XU Mingzhe;ZHANG Xianhua(Chuzhou Institute for Food and Drug Control,Chuzhou Anhui 239000,China;Anhui Center for Drug Evaluation&Inspection,Hefei Anhui 230051,China;Hefei Cosource Pharmaceuticals Inc,Hefei Anhui 230088,China;National Institutes for Food and Drug Control,Beijing 100050,China;Department of Pharmacy,Peking University Third Hospital,Beijing 100191,China)

机构地区：[1]滁州市食品药品检验中心,安徽滁州239000 [2]安徽省药品审评查验中心,安徽合肥230051 [3]合肥合源药业有限公司,安徽合肥230088 [4]中国食品药品检定研究院,北京100050 [5]北京大学第三医院药剂科,北京100191

出　　处：《中国药物警戒》2023年第4期370-373,378,共5页Chinese Journal of Pharmacovigilance

基　　金：国家重点研发计划(SQ2022YFC3401205)。

摘　　要：目的对琥珀酸美托洛尔中潜在的环氧乙烷类基因毒性杂质含量进行测定。方法采用高效液相色谱法测定琥珀酸美托洛尔中含有环氧乙烷结构的杂质XI含量。色谱柱采用Wondasil C_(18)-WR柱(250 mm×4.6 mm,5.0μm),以流动相A为缓冲液(取磷酸二氢钾2.72 g,高氯酸钠一水合物6.13 g,加水1000 mL溶解后,用1.0 mol·L^(-1)氢氧化钠溶液调pH值至6.0),流动相B为甲醇的梯度洗脱,流速1.0 mL·min^(-1),进样量40μL,柱温30℃,检测波长280 nm。结果杂质XI在线性范围为0.8523~6.8183μg·mL^(-1)内,r=0.9999,检测限浓度为0.4261μg·mL^(-1),定量限浓度为0.8523μg·mL^(-1),平均回收率为94.21%。结论本研究准确可靠、专属性强且重现性好,可为琥珀酸美托洛尔中潜在的环氧乙烷类基因毒性杂质的质量控制和安全性评价提供科学依据。Objective To establish an HPLC method for the determination of ethylene oxide genotoxic impurity XI in metoprolol succinate.Methods The Wondasil C_(18)-WR(4.6 mm×250 mm,5.0μm)column was used.The mobile phase consisted of methanol and buffer(potassium dihydrogen phosphate 2.72 g,sodium perchlorate monohydrate 6.13 g,dissolved in 1000 mL water,with pH adjusted to 6.0 with 1.0 mol·L^(-1)sodium hydroxide solution)under gradient elution.The flow rate was 1.0 mL·min^(-1),the injection volume was 40μL,the column temperature was 30℃and the detection wavelength was 226 nm.Results The linear range of impurity XI was 0.8532 to 6.8183μg·mL^(-1)(r=0.9999).The detection limit was 0.4261μg·mL^(-1),with a quantitative limit of 0.8523μg·mL^(-1).The average recovery was 94.21%.Conclusion This method is highly specific,sensitive and user-friendly,which can be used for the determination of genotoxic impurity of ethylene oxide in metoprolol succinate.

关 键 词：琥珀酸美托洛尔 环氧乙烷类 基因毒性 杂质 梯度洗脱 含量测定 高效液相色谱法 专属性 

分 类 号：R917[医药卫生—药物分析学]