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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。
A HPLC method was established for the quality control of biapenem and its impurities. A Dikma Diamonsil C18 (250 mm × 4.6 mm, 5 μm) column was used. The mobile phase was acetonitrile-0.1% triethylamine (1:99, v / v) and the detection wavelength was 220 nm. The linear range of biapenem was (0.05-10.0) mg / mL (r ~ 2 = 0.999). The minimum detectable limit (LOD) and the minimum limit of quantitation (LOQ) ) And 18.5 ng (S / N = 10). The intra-day precision (RSD) of biapenem’s maximum impurity and total impurity were 1.84% and 3.37%, respectively 4.84% and 7.58% respectively (n = 9). The test solution was stable at 4 ℃ for 6 h. Using HPLC-DAD data, a two-dimensional chromatographic spectral correlation analysis technique was used to achieve mass-controlled analysis of the chromatographic peaks in the HPLC-UV chromatogram and the chromatographic peaks in the LC-MS chromatogram without impurity reference substance Recognize. The four chromatographic peaks in the control chromatogram with relative retention times of 0.528, 0.743, 1.062 and 2.817 were identified as the hydrolysates and dimers of biapenem. This method provides a new way to identify chromatographic peaks in conventional HPLC-UV chromatograms.