2D-LC-IT-TOF-MS/MS用于国产阿莫西林颗粒聚合物杂质一致性评价

Evaluate the Consistency of Polymers in Domestic Amoxicillin Granules by 2D-LC-IT-TOF-MS/MS

目的建立高效液相色谱法测定国产制剂阿莫西林颗粒中聚合物杂质含量,用二维液相-在线脱盐-质谱联用仪验证分离杂质结构;产品测定结果与原研制剂对比,考察产品质量一致性。方法色谱柱:Thermo Hypersil GOLD C18(250 mm×4.6 mm,5μm);检测波长:230 nm;柱温:35℃;流速:1.0 mL/min;进样量:20μL;流动相:0.05 mmol/L磷酸盐缓冲液-乙腈,梯度洗脱。结果首次分离并鉴定出阿莫西林颗粒中四聚、五聚、六聚聚合物杂质;测定结果批次间稳定,国产制剂低于原研制剂在同等测定条件下杂质检出量。结论建立的方法灵敏度高、结果准确,可有效控制阿莫西林颗粒中聚合物杂质;考察的国产阿莫西林颗粒制剂工艺稳定,聚合物杂质含量控制优于原研制剂。

Objective To establish a high performance liquid chromatography method for the determination of polymers in amoxicillin granules,and to verify the separation of impurity structures by two-dimensional liquid chromatography-online desalination-mass spectrometry,the product determination results were compared with the original preparation agent,and the consistency of product quality was investigated.Methods The chromatographic column was Thermo Hypersil GOLD C18(250 mm×4.6 mm,5μm);detection wavelength:230 nm;column temperature:35℃;flow rate:1.0 mL/min;sample size:20μL;mobile phase:0.05 mmol/L phosphate buffer-acetonitrile,gradient elution.Results Tetramer,pentamer and hexamer polymer impurities in amoxicillin granules were isolated and identified for the first time.The results were stable from batch to batch,and the domestic preparation was lower than the original preparation under the same testing conditions.Conclusion The established method has high sensitivity and accurate results,and can effectively control the polymer impurity in amoxicillin granules.The domestic amoxicillin granules preparation investigated has stable process and better control of polymer impurity content than the original preparation.