Establishment of an HPLC method for the analysis of biapenem and its impurities  

比阿培南及杂质质控HPLC分析方法的建立(英文)

作　　者：王楠[1] 李春凤 张斗胜[1] 胡昌勤[1] 

机构地区：[1]中国药品生物制品检定所,北京100050

出　　处：《Journal of Chinese Pharmaceutical Sciences》2011年第2X期171-180,共10页中国药学（英文版）

基　　金：National Key New Drug R&D Program Foundation of China(Grant No.2009ZX09313-027).

摘　　要：An HPLC method for routine quality control of biapenem was established.A Dikma Diamonsil C_(18) column(250mm×4.6 mm,5μm) was used with diode array detection and single wavelength detection at 220 nm.The mobile phase was consisted of acetonitrile-0.1%triethylamine water(1:99,v/v).The liner range for biapenem quantification was 0.05-10.0 mg/mL(r^2= 0.999). The LOD and LOQ of impurity were 4.8 ng(S/N = 3) and 18.5 ng(S/N = 10),respectively.Intra-day RSD of main impurity and total impurity were 1.84%and 3.37%(n = 3);inter-day RSD of main impurity and total impurity were 4.84%and 7.58% (n = 9).The test solution was stable when stored at 4℃for 6 h.The impurity peaks of biapenem can be identified by chromatographic spectral correlation analysis using high-performance liquid chromatography-diode array detection data from the quality control method by calculating correlation coefficients without reference standards.Two hydrolysis degradation products with relative retention times(RRTs) of 0.528 and 0.743,two dimers with RRTs of 1.062 and 2.817 were identified in the quality control chromatogram.It provides a new way to identify impurity peaks by the routine HPLC-UV method.建立了适用于比阿培南及其杂质质量控制的HPLC分析方法。采用Dikma Diamonsil C_(18)(250 mm×4.6 mm,5μm)色谱柱,流动相为乙腈-0.1%三乙胺溶液(1:99,v/v),二极管阵列检测器检测波长为220 nm。比阿培南的线性范围为(0.05-10.0)mg/mL(r^2=0.999);杂质的最低检出限(LOD)和最低定量限(LOQ)分别为4.8 ng(S/N=3)和18.5 ng(S/N=10);测定比阿培南最大杂质和总杂质的日内精密度(RSD)分别为1.84%和3.37%(n=3),日间精密度(RSD)分别为4.84%和7.58%(n=9);供试品溶液在4℃放置6 h稳定。利用HPLC-DAD数据,采用二维色谱光谱相关分析技术,在没有杂质对照品的情况下,实现了质控分析HPLC-UV色谱图中的色谱峰与LC-MS色谱图中的色谱峰的相互识别。质控色谱图中相对保留时间为0.528,0.743,1.062和2.817的4个色谱峰结构被确认,分别为比阿培南的水解产物和二聚体。该方法为鉴别常规HPLC-UV色谱图中的色谱峰提供了新思路。

关 键 词：BIAPENEM HPLC-DAD Two-dimensional chromatographic spectral correlative map Identification IMPURITIES 

分 类 号：R927.2[医药卫生—药学]