二维柱切换高效液相色谱法同时测定阿立哌唑中3种基因毒性杂质  

Simultaneous determination of three genotoxic impurities in aripiprazole by two-dimensional column switching high performance liquid chromatography

作　　者：周琳 吴弢[2] 楼永明 Zhou Lin;Wu Tao;Lou Yong-ming(Devision of Chemical Drug Inspection,Fujian Institute for Food and Drug Quality Control,Fuzhou 350001,China;Department of Cervical Thyroid and Breast Surgery,The People’s Hospital Affiliated to Fujian University of Chinese Medicine,Fuzhou 350001,China)

机构地区：[1]福建省食品药品质量检验研究院化学药品检验所,福州350001 [2]福建中医药大学附属人民医院颈部甲状腺乳腺外科,福州350001

出　　处：《中国药物应用与监测》2024年第6期867-870,共4页Chinese Journal of Drug Application and Monitoring

摘　　要：目的建立柱切换高效液相色谱法测定阿立哌唑中的3种基因毒性杂质。方法杂质初步分离:一维色谱柱为Agilent ZORBAX SB-C18,规格4.6 mm×150 mm,5μm,以乙腈-0.05%三氟乙酸(40∶60)为流动相,流速1 mL·min^(-1),波长254 nm,柱温40℃,进样体积50μL,切换时间为12~18 min;杂质分析:二维色谱柱为Agilent Eclipse XDB-C8(4.6 mm×150 mm,5μm),色谱条件同一维色谱。结果杂质7-(4-溴丁氧基)-3,4-二氢-2(1H)-喹诺酮(PPA-A)、6-(4-溴丁氧基)-3,4-二氢-2(1H)-喹诺酮(PPA-ZP)和5-(4-溴丁氧基)-3,4-二氢-2(1H)-喹诺酮(PPA-ZQ)分别在0.1035~0.5175μg·mL^(-1)(r=0.9997)、0.1023~0.5115μg·mL^(-1)(r=0.9990)和0.1066~0.5330μg·mL^(-1)(r=0.9998)范围内线性关系良好,重复性和稳定性相对标准偏差(RSD)均<3.6%,平均回收率为98.9%~103.4%,RSD不超过3.5%,定量限均为0.1μg·mL^(-1),检测限均为0.04μg·mL^(-1)。结论该方法专属性强,能有效分离杂峰干扰,改善基线噪音,提高检测灵敏度,降低经济成本,为阿立哌唑的临床安全性和质量控制提供新的技术支持。Objective To establish a method of column switching high-performance liquid chromatography for the determination of three genotoxic impurities in aripiprazole.Methods For preliminary separation,an Agilent ZORBAX SB-C18 column(4.6 mm×150 mm,5μm)was used as one-dimensional chromatographic column,and acetonitrile-0.05%trifluoroacetic acid(40:60)was set as mobile phase.The flow rate was 1.0 mL·min-1and the injection volume was 50μL.The detection wavelength was set at 254 nm with column temperature at 40℃.The switching time was from 12 to 18 minutes.For impurity analysis,two-dimensional chromatographic separation was conducted on an Agilent Eclipse XDB-C8 column(4.6 mm×150 mm,5μm),and other chromatographic conditions were the same with one-dimensional chromatography.Results The impurities 7-(4-bromobutoxy)-3,4-dihydro-2(1H)-quinolinone(PPA-A),6-(4-bromobutoxy)-3,4-dihydro-2(1H)-quinolinone(PPA-ZP)and 5-(4-bromobutoxy)-3,4-dihydro-2(1H)-quinolinone(PPA-ZQ)showed favorable linear relationship in the range of 0.1035~0.5175μg·mL^(-1)(r=0.9997),0.1023~0.5115μg·mL^(-1)(r=0.9990)and 0.1066~0.5330μg·mL^(-1)(r=0.9998)respectively.Both the RSD of repeatability and stability were less than 3.6%.The average recoveries were 98.9%~103.4%with RSD not more than 3.5%.The limit of quantification was 0.1μg·mL^(-1) and that of detection was 0.04μg·mL^(-1).Conclusion This method shows strong specificity,which can be used to effectively separate impurities,improve baseline noise,enhance detection sensitivity and reduce economic costs.Therefore,it provides a new technical support for the clinical safety and quality control of aripiprazole.

关 键 词：阿立哌唑 柱切换 基因毒性杂质 高效液相色谱 质量控制 

分 类 号：O657.72[理学—分析化学] TQ460.72[理学—化学]