UPLC与HPLC法测定阿托伐他汀钙及其制剂中的有关物质  

Determination of related substances in atorvastatin calcium and its preparation by UPLC and HPLC

作　　者：周怡[1] 高青 尚悦[1] 付龙[2] 刘颖 宋彬彬 郭伟[1,2] 钱忠直 ZHOU Yi;GAO Qing;SHANG Yue;FU Long;LIU Ying;SONG Bin-bin;GUO Wei;QIAN Zhong-zhi(Chinese Pharmacopeia Commission, Beijing 100061, China;ChP-Waters Joint Open Laboratory, Beijing 100061, China;Beijing Institute of Drug Control, Beijing 102206, China)

机构地区：[1]国家药典委员会,北京100061 [2]ChP-Waters联合开放实验室,北京100061 [3]北京市药品检验所,北京102206

出　　处：《药物分析杂志》2018年第4期720-727,共8页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立测定阿托伐他汀钙有关物质及含量的超高效液相色谱法(UPLC)和高效液相色谱法(HPLC),并对方法及测定结果进行比较。方法:UPLC法,采用Acquity BEH Shield RP18色谱柱(150 mm×2.1 mm,1.7μm),流速0.4 mL·min^(-1);HPLC法,采用Symetry Shield RP18色谱柱(250 mm×4.6 mm,5μm),流速1.5 mL·min^(-1)。两方法均以20 mmol·L^(-1)醋酸铵溶液(用冰醋酸调节pH为4.0)为流动相A,乙腈-四氢呋喃(95∶5)为流动相B,梯度洗脱,检测波长254 nm,柱温35℃。结果:UPLC法和HPLC法测定有关物质在一定范围内均呈现良好线性,r>0.999,加样回收率、精密度和样品测定结果基本无差异;UPLC检测下限略低于HPLC检测下限,主峰与非对映异构体(杂质B)分离度优于HPLC法,UPLC法测定时间为17 min,HPLC法为50 min,UPLC法溶剂使用量减少12倍。用建立的UPLC和HPLC方法对阿托伐他汀钙5个企业10批样品,阿托伐他汀钙片剂4个企业14批样品以及阿托伐他汀钙胶囊1个企业6批样品进行有关物质检查,结果无显著差异。结论:UPLC和HPLC 2种方法准确性、精密度、线性等验证试验结果以及样品测定结果基本一致;UPLC法测定阿托伐他汀钙有关物质和含量快速、灵敏度高,分离度好,更环保。Objective：To establish UPLC and HPLC method for the determination of seven related substances in atorvastatin calcium and its preparation,and to compare the two methods as well as the determination results.Methods：A gradient UPLC system was used in the quantitative analysis of seven compounds on Acquity BEH Shield RP18 column（2.1 mm×100 mm,1.7 μm）,using acetonitrile-tetrahydrofuran-ammonium acetate buffer（pH 4.0） as mobile phase,with a flow rate of 0.4 mL·min^-1.An HPLC method was conducted on Symetry Shield RP18 column（4.6 mm×250 mm,5 μm）,with flow rate of 1.0 mL·min^-1 and the same mobile phase as the UPLC method.The wavelength and column temperature were set at 254 nm and 35 ℃,respectively in both methods.In order to compare the two methods,resolution,linearity,repeatability,recovery,limit of detection,force degradation tests,stability and the content of the seven compounds were investigated.Results：The linear relationship between the concentration and peak areas of the seven compounds were all good（r0.999）.There were no significant difference between the analytical validation（accuracy and repeatability） and impurities detection results of the two methods.UPLC shows shorter analysis time（1/3 of HPLC analysis time）,less solvent（1/12）,better resolution between main peak and impurity B peak,lower limits of detection.The results of two methods on related substance test for all samples have no significant differences.Conclusion：Both of the methods show almost the same results.The UPLC method is more efficient,accurate,sensitive and environmental protective.

关 键 词：有关物质 阿托伐他汀钙 降血脂药 超高效液相色谱 高效液相色谱 梯度洗脱 方法验证 方法转换 方法比较 

分 类 号：R917[医药卫生—药物分析学]