注射用美罗培南中聚合物杂质测定及其评价

Determination of the Polymers in Meropenem for Injection by Size Exclusion Chromatography (HPSCE) and Evaluation of Drug Quality

目的建立高效分子排阻色谱法(HPSEC)测定注射用美罗培南中聚合物杂质含量,并用液-质联用仪(LC-MS)对聚合物杂质进行初步定性。方法采用TSKgel G2000SWXL色谱柱,以p H 7. 0的0. 005 mol·L^-1磷酸盐缓冲液[0. 005 mol·L^-1磷酸氢二钠-0. 005 mol·L^-1磷酸二氢钠(61∶39)]为流动相;检测波长为254 nm;流速为0. 8 m L·min^-1;柱温为25℃。结果在该条件下美罗培南峰与聚合物峰分离良好;美罗培南浓度在2. 54~50. 83μg·m L^-1内得回归方程:Y=9. 095 3X-2. 215 0,相关系数r2=0. 999 6 (n=6),浓度与峰面积呈良好的线性关系;本法以美罗培南的最小定量限(S/N=10)为0. 508μg·m L^-1。同时采用TSKgel G2000SWXL柱与反向HPLC-C18柱实现二维柱切换技术,再联合质谱对聚合物杂质进行测定,初步确定聚合物的结构为二聚物、三聚物和同分异构体。结论本方法简便、准确、灵敏、可靠,更能有效的测定美罗培南中聚合物的含量,适用于不同厂家上市药品的再评价。

OBJECTIVE To establish a size exclusion chromatography( HPSCE) method for the determination of the polymers in meropenem for injection. METHODS The analysis was carried out using a TSKgel G2000 SWXL column( 7. 8 mm × 30 cm,5 μm).The mobile phase was pH 7. 0 phosphate buffer solution( 0. 005 mol·L^-1 disodium hydrogen orthophosphate -0. 005 mol·L^-1 sodium dihydrogen phosphate,61∶ 39,V/V). The flow rate was 0. 8 mL·min^-1. The detection wavelength was 254 nm. The column temperature was 25 ℃. RESULTS The polymers were completely separated from meropenem. The calibration curve of meropenem was linear within the range of 2. 54-50. 83 μg·mL^-1( r = 0. 999 6,n = 6). The specificity of the HPSEC was checked by switching the effluent of each peak on the GFC to a C18 column and analyzing the effluent by LC-MS. CONCLUSION This method is simple,accurate,sensitive,reliable and applicable for the determination of the polymers of meropenem,and can be applied to the drug quality evaluation.