Impurity Profiling of a Novel β-Lactam Enhancer: Zidebactam

Autor: Vinod K. Ahirrao, Vipul P. Rane, Kiran R. Patil, Rajiv A. Jadhav, Ravindra D. Yeole
Rok vydání: 2019
Předmět:
Zdroj: Chromatographia. 83:423-437
ISSN: 1612-1112
0009-5893
DOI: 10.1007/s10337-019-03845-3
Popis: 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.
Databáze: OpenAIRE
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