比阿培南开环物杂质的确证及含量测定

Identification of Biapenem Open-ring Impurities and Content Determination of Them

目的：确证比阿培南中开环物杂质并建立其含量测定方法。方法：采用液相色谱．质谱（LC．MS）联用法确证比阿培南中开环物杂质，LC条件：色谱柱为GL Sciences C18流动相A为0．01mol／L醋酸铵溶液，流动相B为乙腈，梯度洗脱；质谱条件：电喷雾离子源，正离子模式采集数据。采用高效液相色谱（HPLC）法测定杂质含量，色谱柱为Kromasil100．5C18 流动相为O．01mol／L四丁基溴化铵溶液．乙腈．三乙胺（980：20：2，pH6．0），检测波长为254nlil。开环物A、B含量均采用自身对照法计算。结果：LC-MS法证明m／z为369、397的离子峰分别为比阿培南开环物A、B；在建立的HPLC色谱条件下，比阿培南、比阿培南开环物B检测质量浓度线性范围分别为0．077～1．546mg／ml、0．765-22．95gg／ml（r=0．9955、0．9999），比阿培南开环物B平均回收率为100．5％（RSD=0．7％，n=3）。结论：建立的方法操作简便、结果可靠，可用于比阿培南中杂质开环物的检查。

OBJECTIVE： To confirm biapenem open-ring impurities and to establish the method for the content determination of them. METHODS： LC-MS was adopted to identify biapenem open-ring impurities. The chromatographic condition of LC： GL Sciences C18 with 0.01 mol/L tetrabutyl ammonium bromide as mobile phase A and acetonitrile as mobile phase B （gradient elu- tion）. The chromatographic condition of MS： ESI, positive ion mode. HPLC was adopted to determine the content of impurities. The determination was performed on Kromasil 100-5 C18 column with mobile phase consisted of 0.01 mol/L ammonium acetate-ace- tonitrile-triethylamine （980：20：2, pH 6.0） with detection wavelength at 254 nm. The content of open-ring impurities A and B were calculated by self-control method. RESULTS： Results of LC-MS analyses showed that the fragment ions at m/z 369 and 397 were open-ring impurities A and B, respectively. Under HPLC, the linear ranges of biapenem and open-ring impurity B were 0.077-1.546 mg/ml （r=0.995 5） and 0.765-22.95 p.g/ml （r=0.999 9）. Average recovery of biapenem open-ring impurity B was 100.5% （RSD= 0.7%, n=3）. CONCLUSIONS： The method is simple and reliable, and it is applicable for the determination of biapenem open- ring impurities.