一测多评法检测头孢克洛胶囊中3种已知杂质  

Detection of Three Known Impurities in Cefaclor Capsules by QAMS

作　　者：路惬楠 张素平 王柳 张轶华 LU Qienan;ZHANG Suping;WANG Liu;ZHANG Yihua(Hebei Institute for Drug and Medical Device Control·NMPA Key Laboratory for Quality Control and Evaluation of Generic Drug,Shijiazhuang,Hebei,China 050200)

机构地区：[1]河北省药品医疗器械检验研究院·国家药品监督管理局仿制药质量控制与评价重点实验室,河北石家庄050200

出　　处：《中国药业》2023年第24期81-85,共5页China Pharmaceuticals

基　　金：中央引导地方科技发展资金项目[216Z2605G]。

摘　　要：目的建立同时检测头孢克洛胶囊中3种已知杂质的一测多评法。方法采用高效液相色谱法,色谱柱为Waters Sunfire C18柱(250 mm×4.6 mm,5μm);流动相为0.78%磷酸二氢钠溶液(pH 4.0,A)-[0.78%磷酸二氢钠溶液(pH 4.0)-乙腈(55︰45,V/V),B],梯度洗脱;流速为1.0 mL/min;检测波长为220 nm;柱温为25℃;进样量为10μL。以头孢克洛为内参物,计算3种已知杂质的相对校正因子,测定含量并与外标法测定结果比较。结果头孢克洛δ-3-异构体、水合羟基化头孢克洛、杂质Ⅰ质量浓度分别在2.79~55.75μg/mL、1.54~30.80μg/mL、2.65~53.02μg/mL范围内与峰面积线性关系良好;检测限分别为0.14,0.15,0.13 ng,定量限分别为0.42,0.46,0.40 ng;精密度、稳定性、重复性试验结果的RSD均小于2.0%(n=6);平均加样回收率分别为99.78%,102.79%,101.02%,RSD分别为1.90%,0.75%,1.01%(n=9);相对校正因子分别为0.83,1.07,1.34。一测多评法与外标法对3种杂质含量的测定结果基本一致。结论所建立的方法操作简单,结果准确,可用于头孢克洛胶囊的杂质检测。Objective To establish a quantitative analysis of multi-components by single marker(QAMS)method for the simultaneous detection of three known impurities in Cefaclor Capsules.Methods High-performance liquid chromatography(HPLC)method was adopted.The chromatographic column was Waters Sunfire C18 column(250 mm×4.6 mm,5μm),the mobile phase was 0.78%sodium dihydrogen phosphate solution(pH 4.0,A)-[0.78%sodium dihydrogen phosphate solution(pH 4.0)-acetonitrile(55∶45,V/V),B],with gradient elution,the flow rate was 1.0 mL/min,the detection wavelength was 220 nm,the column temperature was 25℃,and the injection volume was 10μL.The relative correction factors of three known impurities were calculated with cefaclor as the internal reference,the content of the impurities was determined and compared with that by the external standard method(ESM).Results The linear ranges of cefaclorδ-3-isomer,hydrated hydroxylated cefaclor and impurityⅠwere 2.79-55.75μg/mL,1.54-30.80μg/mL,2.65-53.02μg/mL respectively.The limits of detection(LOD)were 0.14,0.15,0.13 ng,and the limits of quantification(LOQ)were 0.42,0.46,0.40 ng,respectively.The RSDs of precision,stability and repeatability tests were all lower than 2.0%(n=6).The average recovery rates were 99.78%,102.79%,101.02%with RSDs of 1.90%,0.75%and 1.01%(n=9)respectively.The relative correction factors were 0.83,1.07,1.34,respectively.The content of three impurities determined by QAMS method and ESM was similar.Conclusion The established method is simple and accurate,which can be used for the impurity detection of Cefaclor Capsules.

关 键 词：一测多评法 高效液相色谱法 相对校正因子 头孢克洛胶囊 杂质 

分 类 号：R917[医药卫生—药物分析学] R927[医药卫生—药学]