Abstract Zidebactam (ZID) is a novel drug in clinical development; it potentiates the antibacterial activity of β-lactam antibiotics. Two reversed phase liquid chromatographic (RP-LC) methods were developed for ZID; a mass spectrometer (MS) compatible method for identification and another UV detection method for the quantification of impurities. Four impurities and three degradation products (DPs) were identified using LC–MS/MS. Both methods were developed on Hydrosphere C18 stationary phase which was found to be unique for the purpose due to its hydrophilic surface. The chromatographic separation of ZID and impurities was achieved in gradient mode using mobile phase consisting of ammonium formate in LC–MS/MS studies and ammonium dihydrogen phosphate in UV method. Acetonitrile (ACN) was employed as an organic solvent. ZID was subjected to hydrolytic, oxidative, photolytic and thermal stress conditions. The degradation was observed in acidic, basic and oxidative conditions. The UV method was validated. The method was accurate and precise to quantify impurities; accuracy was greater than 99.8% with precision of less than 4%. The method was highly sensitive to detect impurities as low as 1.4 ng on column. The developed method was employed for quality control and stability studies of the new drug substance during pre-clinical and clinical studies. The same method was also adapted for analysis of a parenteral drug product. Graphic abstract

中文翻译：

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新型 β-内酰胺增强剂的杂质分析：齐德巴坦

摘要 齐德巴坦（ZID）是一种临床开发的新药；它增强了β-内酰胺类抗生素的抗菌活性。开发了两种用于 ZID 的反相液相色谱 (RP-LC) 方法；用于鉴定的质谱仪 (MS) 兼容方法和用于定量杂质的另一种 UV 检测方法。使用 LC-MS/MS 鉴定了四种杂质和三种降解产物 (DP)。这两种方法都是在 Hydrosphere C18 固定相上开发的，由于其亲水表面，该固定相被发现是独一无二的。ZID 和杂质的色谱分离是在梯度模式下使用由 LC-MS/MS 研究中的甲酸铵和 UV 方法中的磷酸二氢铵组成的流动相实现的。乙腈 (ACN) 用作有机溶剂。ZID 经受水解、氧化、光解和热应力条件。在酸性、碱性和氧化条件下观察到降解。紫外线方法得到验证。该方法准确、精密地定量杂质；准确度大于99.8%，精度小于4%。该方法对检测柱上低至 1.4 ng 的杂质高度敏感。在临床前和临床研究期间，开发的方法用于新原料药的质量控制和稳定性研究。同样的方法也适用于肠胃外药物产品的分析。图形摘要 准确度大于99.8%，精度小于4%。该方法对检测柱上低至 1.4 ng 的杂质高度敏感。在临床前和临床研究期间，开发的方法用于新原料药的质量控制和稳定性研究。同样的方法也适用于肠胃外药物产品的分析。图形摘要 准确度大于99.8%，精度小于4%。该方法对检测柱上低至 1.4 ng 的杂质高度敏感。在临床前和临床研究期间，开发的方法用于新原料药的质量控制和稳定性研究。同样的方法也适用于肠胃外药物产品的分析。图形摘要